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Irannejadrankouhi S, Mivehchi H, Eskandari-Yaghbastlo A, Nejati ST, Emrahoglu S, Nazarian M, Zahedi F, Madani SM, Nabi-Afjadi M. Innovative nanoparticle strategies for treating oral cancers. Med Oncol 2025; 42:182. [PMID: 40285805 DOI: 10.1007/s12032-025-02728-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2025] [Accepted: 04/14/2025] [Indexed: 04/29/2025]
Abstract
Conventional therapies for oral squamous cell carcinoma (OSCC), a serious worldwide health problem, are frequently constrained by inadequate targeting and serious side effects. Drug delivery systems (DDS) based on nanoparticles provide a possible substitute by improving drug stability, target accuracy, and lowering toxicity. By addressing issues like irregular vasculature and thick tumor matrices, these methods allow for more effective medication administration. For instance, the delivery of cisplatin via liposomes, as opposed to free drug formulations, results in a 40% improvement in tumor suppression. Likewise, compared to traditional techniques, poly (lactic-co-glycolic acid) (PLGA) nanoparticles can produce up to 2.3 times more intertumoral drug accumulation. These platforms have effectively administered natural substances like curcumin and chemotherapeutics like paclitaxel, enhancing therapeutic results while reducing adverse effects. Despite their promise, several types of nanoparticles have drawbacks. For example, PLGA nanoparticles have scaling issues because of their complicated production, whereas liposomes are quickly removed from circulation. In preclinical investigations, functionalized nanoparticles-like EGFR-targeted gold nanoparticles-improve selectivity and effectiveness by obtaining up to 90% receptor binding. By preferentially accumulating in tumors via the increased permeability and retention (EPR) effect, nanoparticles also improve immunotherapy and radiation. Mechanistically, they increase the death of cancer cells by causing DNA damage, interfering with cell division, and producing reactive oxygen species (ROS). There are still issues with toxicity (such as the buildup of metallic nanoparticles in the liver) and large-scale manufacturing. Nevertheless, developments in multifunctional platforms and stimuli-responsive nanoparticles show promise for getting over these obstacles. These developments open the door to more individualized and successful OSCC therapies.
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Affiliation(s)
| | - Hassan Mivehchi
- Faculty of Dentistry, University of Debrecen, Debrecen, Hungary
| | | | | | - Sahand Emrahoglu
- School of Dental Medicine, Case Western Reserve University, Cleveland, OH, USA
| | - Mohammad Nazarian
- Faculty of Dentistry, Belarusion State Medical University, Minsk, Belarus
| | - Farhad Zahedi
- Institute of Molecular Biophysics, Florida State University, 91 Chieftan Way, Tallahassee, FL, 32306, USA
| | - Seyed Mahdi Madani
- Faculty of Dentistry, Isfahan University of Medical Sciences, Isfahan, Iran.
| | - Mohsen Nabi-Afjadi
- Department of Biochemistry, Faculty of Biological Sciences, University of Tarbiat Modares, Tehran, Iran.
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Tripathi D, Pandey P, Sharma S, Rai AK, Prabhu B.H. M. Advances in nanomaterials for precision drug delivery: Insights into pharmacokinetics and toxicity. BIOIMPACTS : BI 2024; 15:30573. [PMID: 40256227 PMCID: PMC12008503 DOI: 10.34172/bi.30573] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/08/2024] [Revised: 08/27/2024] [Accepted: 09/17/2024] [Indexed: 04/22/2025]
Abstract
By integrating the cutting-edge principles of nanotechnology with medical science, nanomedicine offers unprecedented opportunities to develop advanced drug delivery systems that surpass the limitations of conventional therapies. These nanoscale systems are designed to enhance treatments' efficacy, specificity, and safety by optimizing pharmacokinetics and biodistribution, ensuring that therapeutic agents reach their intended targets with minimal side effects. The article provides an in-depth analysis of nanomaterials' pivotal role in overcoming challenges related to drug delivery, including the ability to bypass biological barriers, improve bioavailability, and achieve controlled release of drugs. Despite these promising advancements, the transition of nanomedicine from research to clinical practice faces significant hurdles. The review highlights key obstacles such as patient heterogeneity, physiological variability, and the complex ADME (Absorption, Distribution, Metabolism, Excretion) profiles of nanocarriers, which complicate treatment predictability and effectiveness. Moreover, the article addresses the issues of limited tissue penetration, variable patient responses, and the need for standardized protocols in nanomaterial characterization, all of which hinder the widespread clinical adoption of nanomedicine. Nevertheless, the potential of nanomedicine in revolutionizing personalized cancer therapy remains immense. The article advocates for increased translational research and international collaboration to overcome these challenges, paving the way for fully realizing nanomedicine's capabilities in precision oncology and beyond.
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Affiliation(s)
- Devika Tripathi
- PSIT-Pranveer Singh Institute of Technology (Pharmacy), Kanpur Uttar Pradesh, 208002, India
| | - Prashant Pandey
- Department of Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University, Lucknow, Uttar Pradesh 226025, India
- Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta T6G 2E1, Canada
| | - Sakshi Sharma
- PSIT-Pranveer Singh Institute of Technology (Pharmacy), Kanpur Uttar Pradesh, 208002, India
| | - Awani K Rai
- PSIT-Pranveer Singh Institute of Technology (Pharmacy), Kanpur Uttar Pradesh, 208002, India
| | - Manjunatha Prabhu B.H.
- Department of Food Protection and Infestation Control, CSIR- Central Food Technological Research Institute (CFTRI), Mysore-570012, Karnataka, India
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Yang L, Li H, Luo A, Zhang Y, Chen H, Zhu L, Yang D. Macrophage membrane-camouflaged pH-sensitive nanoparticles for targeted therapy of oral squamous cell carcinoma. J Nanobiotechnology 2024; 22:168. [PMID: 38610015 PMCID: PMC11015647 DOI: 10.1186/s12951-024-02433-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2023] [Accepted: 03/22/2024] [Indexed: 04/14/2024] Open
Abstract
BACKGROUND Oral cancer is the most common malignant tumor of the head and neck, and 90% of cases are oral squamous cell carcinoma (OSCC). Chemotherapy is an important component of comprehensive treatment for OSCC. However, the clinical treatment effect of chemotherapy drugs, such as doxorubicin (DOX), is limited due to the lack of tumor targeting and rapid clearance by the immune system. Thus, based on the tumor-targeting and immune evasion abilities of macrophages, macrophage membrane-encapsulated poly(methyl vinyl ether alt maleic anhydride)-phenylboronic acid-doxorubicin nanoparticles (MM@PMVEMA-PBA-DOX NPs), briefly as MM@DOX NPs, were designed to target OSCC. The boronate ester bonds between PBA and DOX responded to the low pH value in the tumor microenvironment, selectively releasing the loaded DOX. RESULTS The results showed that MM@DOX NPs exhibited uniform particle size and typical core-shell structure. As the pH decreased from 7.4 to 5.5, drug release increased from 14 to 21%. The in vitro targeting ability, immune evasion ability, and cytotoxicity of MM@DOX NPs were verified in HN6 and SCC15 cell lines. Compared to free DOX, flow cytometry and fluorescence images demonstrated higher uptake of MM@DOX NPs by tumor cells and lower uptake by macrophages. Cell toxicity and live/dead staining experiments showed that MM@DOX NPs exhibited stronger in vitro antitumor effects than free DOX. The targeting and therapeutic effects were further confirmed in vivo. Based on in vivo biodistribution of the nanoparticles, the accumulation of MM@DOX NPs at the tumor site was increased. The pharmacokinetic results demonstrated a longer half-life of 9.26 h for MM@DOX NPs compared to 1.94 h for free DOX. Moreover, MM@DOX NPs exhibited stronger tumor suppression effects in HN6 tumor-bearing mice and good biocompatibility. CONCLUSIONS Therefore, MM@DOX NPs is a safe and efficient therapeutic platform for OSCC.
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Affiliation(s)
- Lin Yang
- Department of Endodontics, Stomatological Hospital of Chongqing Medical University, Chongqing, 404100, China
- Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Stomatological Hospital of Chongqing Medical University, Chongqing, 404100, China
- Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing, 404100, China
- Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, 426 Songshi North Road, Yubei District, Chongqing, 401147, China
| | - Hongjiao Li
- Department of Endodontics, Stomatological Hospital of Chongqing Medical University, Chongqing, 404100, China
- Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Stomatological Hospital of Chongqing Medical University, Chongqing, 404100, China
- Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing, 404100, China
- Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, 426 Songshi North Road, Yubei District, Chongqing, 401147, China
| | - Aihua Luo
- Department of Endodontics, Stomatological Hospital of Chongqing Medical University, Chongqing, 404100, China
- Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Stomatological Hospital of Chongqing Medical University, Chongqing, 404100, China
- Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing, 404100, China
- Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, 426 Songshi North Road, Yubei District, Chongqing, 401147, China
| | - Yao Zhang
- Department of Endodontics, Stomatological Hospital of Chongqing Medical University, Chongqing, 404100, China
- Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Stomatological Hospital of Chongqing Medical University, Chongqing, 404100, China
- Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing, 404100, China
| | - Hong Chen
- Department of Endodontics, Stomatological Hospital of Chongqing Medical University, Chongqing, 404100, China
- Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Stomatological Hospital of Chongqing Medical University, Chongqing, 404100, China
- Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing, 404100, China
- Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, 426 Songshi North Road, Yubei District, Chongqing, 401147, China
| | - Li Zhu
- Key Laboratory for Biorheological Science and Technology of Ministry of Education, State and Local Joint Engineering Laboratory for Vascular Implants, Bioengineering College of Chongqing University, Chongqing, 400044, China.
| | - Deqin Yang
- Department of Endodontics, Stomatological Hospital of Chongqing Medical University, Chongqing, 404100, China.
- Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Stomatological Hospital of Chongqing Medical University, Chongqing, 404100, China.
- Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing, 404100, China.
- Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, 426 Songshi North Road, Yubei District, Chongqing, 401147, China.
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Senevirathna K, Jayawickrama SM, Jayasinghe YA, Prabani KIP, Akshala K, Pradeep RGGR, Damayanthi HDWT, Hettiarachchi K, Dorji T, Lucero‐Prisno DE, Rajapakse RMG, Kanmodi KK, Jayasinghe RD. Nanoplatforms: The future of oral cancer treatment. Health Sci Rep 2023; 6:e1471. [PMID: 37547360 PMCID: PMC10397482 DOI: 10.1002/hsr2.1471] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2023] [Revised: 07/16/2023] [Accepted: 07/20/2023] [Indexed: 08/08/2023] Open
Abstract
Background and Aims Cytotoxicity is a key disadvantage of using chemotherapeutic drugs to treat cancer. This can be overcome by encapsulating chemotherapeutic drugs in suitable carriers for targeted delivery, allowing them to be released only at the cancerous sites. Herein, we aim to review the recent scientific developments in the utilization of nanotechnology-based drug delivery systems for treating oral malignancies that can lead to further improvements in clinical practice. Methods A comprehensive literature search was conducted on PubMed, Google Scholar, ScienceDirect, and other notable databases to identify recent peer-reviewed clinical trials, reviews, and research articles related to nanoplatforms and their applications in oral cancer treatment. Results Nanoplatforms offer a revolutionary strategy to overcome the challenges associated with conventional oral cancer treatments, such as poor drug solubility, non-specific targeting, and systemic toxicity. These nanoscale drug delivery systems encompass various formulations, including liposomes, polymeric nanoparticles, dendrimers, and hydrogels, which facilitate controlled release and targeted delivery of therapeutic agents to oral cancer sites. By exploiting the enhanced permeability and retention effect, Nanoplatforms accumulate preferentially in the tumor microenvironment, increasing drug concentration and minimizing damage to healthy tissues. Additionally, nanoplatforms can be engineered to carry multiple drugs or a combination of drugs and diagnostic agents, enabling personalized and precise treatment approaches. Conclusion The utilization of nanoplatforms in oral cancer treatment holds significant promise in revolutionizing therapeutic strategies. Despite the promising results in preclinical studies, further research is required to evaluate the safety, efficacy, and long-term effects of nanoformulations in clinical settings. If successfully translated into clinical practice, nanoplatform-based therapies have the potential to improve patient outcomes, reduce side effects, and pave the way for more personalized and effective oral cancer treatments.
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Affiliation(s)
- Kalpani Senevirathna
- Centre for Research in Oral Cancer, Faculty of Dental SciencesUniversity of PeradeniyaPeradeniyaSri Lanka
| | - Shalindu M. Jayawickrama
- Centre for Research in Oral Cancer, Faculty of Dental SciencesUniversity of PeradeniyaPeradeniyaSri Lanka
| | - Yovanthi A. Jayasinghe
- Centre for Research in Oral Cancer, Faculty of Dental SciencesUniversity of PeradeniyaPeradeniyaSri Lanka
| | - Karunakalage I. P. Prabani
- Centre for Research in Oral Cancer, Faculty of Dental SciencesUniversity of PeradeniyaPeradeniyaSri Lanka
| | - Kushani Akshala
- Department of Agricultural Biology, Faculty of AgricultureUniversity of PeradeniyaPeradeniyaSri Lanka
| | | | | | - Kalani Hettiarachchi
- Centre for Research in Oral Cancer, Faculty of Dental SciencesUniversity of PeradeniyaPeradeniyaSri Lanka
| | - Thinley Dorji
- Department of Internal MedicineCentral Regional Referral HospitalGelegphuBhutan
| | - Don E. Lucero‐Prisno
- Department of Global Health and DevelopmentLondon School of Hygiene and Tropical MedicineLondonUK
| | | | - Kehinde K. Kanmodi
- Faculty of DentistryUniversity of PuthisastraPhnom PenhCambodia
- School of DentistryUniversity of RwandaKigaliRwanda
- School of Health and Life SciencesTeesside UniversityMiddlesbroughUK
- Cephas Health Research Initiative IncIbadanNigeria
| | - Ruwan D. Jayasinghe
- Centre for Research in Oral Cancer, Faculty of Dental SciencesUniversity of PeradeniyaPeradeniyaSri Lanka
- Faculty of DentistryUniversity of PuthisastraPhnom PenhCambodia
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Umapathy VR, Natarajan PM, Swamikannu B. Review of the Role of Nanotechnology in Overcoming the Challenges Faced in Oral Cancer Diagnosis and Treatment. Molecules 2023; 28:5395. [PMID: 37513267 PMCID: PMC10385509 DOI: 10.3390/molecules28145395] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2023] [Revised: 07/01/2023] [Accepted: 07/06/2023] [Indexed: 07/30/2023] Open
Abstract
Throughout the world, oral cancer is a common and aggressive malignancy with a high risk of morbidity, mortality, and recurrence. The importance of early detection in cancer prevention and disease treatment cannot be overstated. Conventional therapeutic strategies have minor difficulties but considerable side effects and unfavourable consequences in clinical applications. Hence, there is a requirement for effective ways for early detection and treatment of oral cancer. At present, numerous forms of nanoparticles have piqued researchers' interest as a potentially useful tool for diagnostic probes and medicinal devices. Because of their inherent physicochemical properties and customizable surface modification, they are able to circumvent some of restrictions and accomplish the intended diagnostic and therapeutic impact. Nanotechnology is a unique field that has revolutionised the industry and is paving the way for new treatments for oral cancer. It can help with a better diagnosis with less harmful substances and is setting current guidelines for treatment. The use of nanotechnology in cancer diagnosis, therapy, and care improves clinical practise dramatically. The different types of nanoparticles that have been developed for the diagnosis and therapy of oral cancers will be covered in this study. The difficulties and potential uses of nanoparticles in the treatment and diagnosis of oral cancer are then highlighted. In order to emphasise existing difficulties and potential remedies for oral cancer, a prospective view of the future is also provided.
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Affiliation(s)
- Vidhya Rekha Umapathy
- Department of Public Health Dentistry, Thai Moogambigai Dental College and Hospital, Dr. M.G.R. Educational and Research Institute, Chennai 600107, Tamil Nadu, India
| | - Prabhu Manickam Natarajan
- Department of Clinical Sciences, Centre of Medical and Bio-Allied Health Sciences and Research, Ajman University, Ajman P.O. Box 346, United Arab Emirates
| | - Bhuminathan Swamikannu
- Department of Prosthodontics, Sree Balaji Dental College and Hospital, BIHER University, Pallikaranai, Chennai 600100, Tamil Nadu, India
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Dorostkar H, Haghiralsadat BF, Hemati M, Safari F, Hassanpour A, Naghib SM, Roozbahani MH, Mozafari MR, Moradi A. Reduction of Doxorubicin-Induced Cardiotoxicity by Co-Administration of Smart Liposomal Doxorubicin and Free Quercetin: In Vitro and In Vivo Studies. Pharmaceutics 2023; 15:1920. [PMID: 37514106 PMCID: PMC10385381 DOI: 10.3390/pharmaceutics15071920] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2023] [Revised: 05/24/2023] [Accepted: 05/26/2023] [Indexed: 07/30/2023] Open
Abstract
Doxorubicin is one of the most effective chemotherapeutic agents; however, it has various side effects, such as cardiotoxicity. Therefore, novel methods are needed to reduce its adverse effects. Quercetin is a natural flavonoid with many biological activities. Liposomes are lipid-based carriers widely used in medicine for drug delivery. In this study, liposomal doxorubicin with favorable characteristics was designed and synthesized by the thin-film method, and its physicochemical properties were investigated by different laboratory techniques. Then, the impact of the carrier, empty liposomes, free doxorubicin, liposomal doxorubicin, and quercetin were analyzed in animal models. To evaluate the interventions, measurements of cardiac enzymes, oxidative stress and antioxidant markers, and protein expression were performed, as well as histopathological studies. Additionally, cytotoxicity assay and cellular uptake were carried out on H9c2 cells. The mean size of the designed liposomes was 98.8 nm, and the encapsulation efficiency (EE%) was about 85%. The designed liposomes were anionic and pH-sensitive and had a controlled release pattern with excellent stability. Co-administration of liposomal doxorubicin with free quercetin to rats led to decreased weight loss, creatine kinase (CK-MB), lactate dehydrogenase (LDH), and malondialdehyde (MDA), while it increased the activity of glutathione peroxidase, catalase, and superoxide dismutase enzymes in their left ventricles. Additionally, it changed the expression of NOX1, Rac1, Rac1-GTP, SIRT3, and Bcl-2 proteins, and caused tissue injury and cell cytotoxicity. Our data showed that interventions can increase antioxidant capacity, reduce oxidative stress and apoptosis in heart tissue, and lead to fewer complications. Overall, the use of liposomal doxorubicin alone or the co-administration of free doxorubicin with free quercetin showed promising results.
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Affiliation(s)
- Hamidreza Dorostkar
- Department of Clinical Biochemistry, Faculty of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd 8916877391, Iran
| | - Bibi Fatemeh Haghiralsadat
- Department of Advanced Medical Sciences and Technologies, Faculty of Paramedicine, Shahid Sadoughi University of Medical Sciences, Yazd 8916877391, Iran
- Medical Nanotechnology and Tissue Engineering Research Center, Yazd Reproductive Sciences Institute, Shahid Sadoughi University of Medical Sciences, Yazd 8916877391, Iran
| | - Mahdie Hemati
- Department of Clinical Biochemistry, Faculty of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd 8916877391, Iran
- Medical Nanotechnology and Tissue Engineering Research Center, Yazd Reproductive Sciences Institute, Shahid Sadoughi University of Medical Sciences, Yazd 8916877391, Iran
| | - Fatemeh Safari
- Department of Physiology, Faculty of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd 8916877391, Iran
- Cardiovascular Research Center, Shahid Sadoughi University of Medical Sciences, Yazd 8916877391, Iran
| | - Azam Hassanpour
- Department of Anatomical Sciences, Faculty of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd 8916877391, Iran
| | - Seyed Morteza Naghib
- Nanotechnology Department, School of Advanced Technologies, Iran University of Science and Technology and Biomaterials and Tissue Engineering Department, Breast Cancer Research Center, Motamed Cancer Institute, IUST, ACECR, Tehran 1684613114, Iran
| | | | - M R Mozafari
- Australasian Nanoscience and Nanotechnology Initiative (ANNI), Monash University LPO, Clayton, VIC 3168, Australia
| | - Ali Moradi
- Department of Clinical Biochemistry, Faculty of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd 8916877391, Iran
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Micheli L, Di Cesare Mannelli L, Mosti E, Ghelardini C, Bilia AR, Bergonzi MC. Antinociceptive Action of Thymoquinone-Loaded Liposomes in an In Vivo Model of Tendinopathy. Pharmaceutics 2023; 15:1516. [PMID: 37242757 PMCID: PMC10222138 DOI: 10.3390/pharmaceutics15051516] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2023] [Revised: 05/14/2023] [Accepted: 05/15/2023] [Indexed: 05/28/2023] Open
Abstract
Tendinopathies represent about 45% of musculoskeletal lesions and they are a big burden in clinics characterized by activity-related pain, focal tendon tenderness and intra-tendinous imaging changes. Many approaches have been proposed for tendinopathies' management (e.g., nonsteroidal anti-inflammatory drugs, corticosteroids, eccentric exercises, laser therapy), unfortunately with very little support of efficacy or serious side effects, thus making the identification of new treatments fundamental. The aim of the study was to test the protective and pain reliever effect of thymoquinone (TQ)-loaded formulations in a rat model of tendinopathy induced by carrageenan intra-tendon injection (20 µL of carrageenan 0.8% on day 1). Conventional (LP-TQ) and hyaluronic acid (HA)-coated TQ liposomes (HA-LP-TQ) were characterized and subjected to in vitro release and stability studies at 4 °C. Then, TQ and liposomes were peri-tendon injected (20 µL) on days 1, 3, 5, 7 and 10 to evaluate their antinociceptive profile using mechanical noxious and non-noxious stimuli (paw pressure and von Frey tests), spontaneous pain (incapacitance test) and motor alterations (Rota rod test). Liposomes containing 2 mg/mL of TQ and covered with HA (HA-LP-TQ2) reduced the development of spontaneous nociception and hypersensitivity for a long-lasting effect more than the other formulations. The anti-hypersensitivity effect matched with the histopathological evaluation. In conclusion, the use of TQ encapsulated in HA-LP liposomes is suggested as a new treatment for tendinopathies.
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Affiliation(s)
- Laura Micheli
- Department of Neuroscience, Psychology, Drug Research and Child Health—NEUROFARBA—Pharmacology and Toxicology Section, University of Florence, Viale G. Pieraccini 6, 50139 Florence, Italy; (L.M.); (L.D.C.M.); (C.G.)
| | - Lorenzo Di Cesare Mannelli
- Department of Neuroscience, Psychology, Drug Research and Child Health—NEUROFARBA—Pharmacology and Toxicology Section, University of Florence, Viale G. Pieraccini 6, 50139 Florence, Italy; (L.M.); (L.D.C.M.); (C.G.)
| | - Elena Mosti
- Department of Chemistry Ugo Schiff, University of Florence, Via Ugo Schiff 6, Sesto Fiorentino, 50019 Florence, Italy; (E.M.); (A.R.B.)
| | - Carla Ghelardini
- Department of Neuroscience, Psychology, Drug Research and Child Health—NEUROFARBA—Pharmacology and Toxicology Section, University of Florence, Viale G. Pieraccini 6, 50139 Florence, Italy; (L.M.); (L.D.C.M.); (C.G.)
| | - Anna Rita Bilia
- Department of Chemistry Ugo Schiff, University of Florence, Via Ugo Schiff 6, Sesto Fiorentino, 50019 Florence, Italy; (E.M.); (A.R.B.)
| | - Maria Camilla Bergonzi
- Department of Chemistry Ugo Schiff, University of Florence, Via Ugo Schiff 6, Sesto Fiorentino, 50019 Florence, Italy; (E.M.); (A.R.B.)
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Burruss CP, Kacker A. The current status of nanotechnological approaches to therapy and drug delivery in otolaryngology: A contemporary review. Laryngoscope Investig Otolaryngol 2022; 7:1762-1772. [PMID: 36544970 PMCID: PMC9764775 DOI: 10.1002/lio2.952] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2022] [Revised: 10/06/2022] [Accepted: 10/09/2022] [Indexed: 12/24/2022] Open
Abstract
Objectives/Hypothesis To summarize the current standing of nanomedicine-based technology, particularly nanoparticles (NPs), for drug delivery and diagnostic mechanisms in otolaryngology and the otolaryngology subspecialties. Methods Literature searches were performed using PubMed and Ovid MEDLINE from 2010 to 2022. The search focused on original articles describing developments and applications of nanotechnology and drug delivery in otology, neurotology, cranial base surgery, head and neck oncology, laryngology, bronchoesophagology, and rhinology. Keyword searches and cross-referencing were also performed. No statistical analysis was performed. Results The PubMed search yielded 29 articles, and two Ovid MEDLINE searches both yielded 7 and 26 articles, respectively. Cross-referencing and keyword searches in PubMed and Google Scholar yielded numerous articles. The results indicate that currently, NPs are the most thoroughly studied nanotechnology for drug delivery and therapy in otolaryngology. Organic NPs have been utilized for drug delivery in otology and head and neck oncology due to their high biocompatibility. Inorganic NPs have similarly been utilized for drug delivery. However, inorganic NPs seem to be studied less extensively in these fields, likely due to an increased risk for heavy metal toxicity. Due to their magnetic properties, inorganic NPs have been utilized for magnetic-guided delivery in otology and thermoradiation and magnetic resonance imaging in head and neck oncology. Applications of nanotechnology to the fields of laryngology, bronchoesophagology, and rhinology have been studied less compared with otology and head and neck oncology. However, researchers have primarily employed NPs and other nanotechnologies such as nanofibers and nanoclusters for drug elution at mucosal surfaces to reduce airway and nasal inflammation. Conclusions Nanomedicine offers potential benefits in the treatment of patients in the field of otolaryngology due to enhanced control over drug release, cell-specific targeting, and the potential to reduce drug toxicity. Future work is needed to ensure the safety of these therapies to integrate this field of research into human therapies.
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Affiliation(s)
| | - Ashutosh Kacker
- Department of Otolaryngology–Head and Neck SurgeryWeill Cornell MedicineNew YorkNew YorkUSA
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9
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Applications of Various Types of Nanomaterials for the Treatment of Neurological Disorders. NANOMATERIALS 2022; 12:nano12132140. [PMID: 35807977 PMCID: PMC9268720 DOI: 10.3390/nano12132140] [Citation(s) in RCA: 40] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/24/2022] [Revised: 06/08/2022] [Accepted: 06/19/2022] [Indexed: 02/07/2023]
Abstract
Neurological disorders (NDs) are recognized as one of the major health concerns globally. According to the World Health Organization (WHO), neurological disorders are one of the main causes of mortality worldwide. Neurological disorders include Alzheimer’s disease, Parkinson′s disease, Huntington′s disease, Amyotrophic lateral sclerosis, Frontotemporal dementia, Prion disease, Brain tumor, Spinal cord injury, and Stroke. These diseases are considered incurable diseases because no specific therapies are available to cross the blood-brain barrier (BBB) and reach the brain in a significant amount for the pharmacological effect in the brain. There is a need for the development of strategies that can improve the efficacy of drugs and circumvent BBB. One of the promising approaches is the use of different types of nano-scale materials. These nano-based drugs have the ability to increase the therapeutic effect, reduce toxicity, exhibit good stability, targeted delivery, and drug loading capacity. Different types and shapes of nanomaterials have been widely used for the treatment of neurological disorders, including quantum dots, dendrimers, metallic nanoparticles, polymeric nanoparticles, carbon nanotubes, liposomes, and micelles. These nanoparticles have unique characteristics, including sensitivity, selectivity, and the ability to cross the BBB when used in nano-sized particles, and are widely used for imaging studies and treatment of NDs. In this review, we briefly summarized the recent literature on the use of various nanomaterials and their mechanism of action for the treatment of various types of neurological disorders.
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10
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Li H, Zhang Y, Xu M, Yang D. Current trends of targeted therapy for oral squamous cell carcinoma. J Cancer Res Clin Oncol 2022; 148:2169-2186. [PMID: 35501496 DOI: 10.1007/s00432-022-04028-8] [Citation(s) in RCA: 44] [Impact Index Per Article: 14.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2022] [Accepted: 04/15/2022] [Indexed: 10/18/2022]
Abstract
Oral squamous cell carcinoma (OSCC) is a malignant disease in the world which has a profound effect on human health and life quality. According to tumor stage and pathological diagnosis, OSCC is mainly treated by combinations of surgery, radiotherapy and chemotherapy. However, traditional treatment methods suffer from some limitations, such as systemic toxicity, limited therapeutic effect and drug resistance. With the rapid development of nanotechnology, nanodrug delivery systems (DDSs) and intelligent DDSs have been widely used in targeted therapy for OSCC. Meanwhile, the newly developed therapeutic techniques such as immunotherapy, gene therapy and bionic technology provide the possibility to realize the active targeted therapy. Here, the latest advances of target therapy for OSCC are reviewed, and their therapeutic remarks, current limits and future prospects are also systematically interpreted. It is believed that active and passive targeted therapies have great potentials for clinical transformation and application of OSCC, which will greatly improve human quality of life.
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Affiliation(s)
- Hongjiao Li
- School and Hospital of Stomatology, College of Stomatology, Chongqing Medical University, Chongqing, 401147, China
| | - Yao Zhang
- School and Hospital of Stomatology, College of Stomatology, Chongqing Medical University, Chongqing, 401147, China
| | - Mengmeng Xu
- School and Hospital of Stomatology, College of Stomatology, Chongqing Medical University, Chongqing, 401147, China
| | - Deqin Yang
- School and Hospital of Stomatology, College of Stomatology, Chongqing Medical University, Chongqing, 401147, China.
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11
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Bollareddy SR, Krishna V, Roy G, Dasari D, Dhar A, Venuganti VVK. Transfersome Hydrogel Containing 5-Fluorouracil and Etodolac Combination for Synergistic Oral Cancer Treatment. AAPS PharmSciTech 2022; 23:70. [PMID: 35132496 DOI: 10.1208/s12249-022-02221-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2021] [Accepted: 01/17/2022] [Indexed: 11/30/2022] Open
Abstract
Oral cancer is one of the most common malignancies with an increased rate of incidence. 5-Fluorouracil (5FU) is an effective chemotherapeutic indicated for oral cancer treatment. Etodolac (Et), a cyclooxygenase-2 inhibitor, can be used as an adjuvant agent to sensitize cancer cells to chemotherapy. The aim of this work was to prepare and characterize 5FU and Et dual drug-loaded transfersomes to treat oral cancer. Transfersomes were prepared by thin-film hydration method and characterized for the average particle size and zeta-potential using dynamic light scattering and scanning electron microscopy techniques. The prepared transfersomes were further characterized for their drug loading, entrapment efficiencies using amicon centrifuge tubes and drug release behavior using cellulose membrane. The synergistic activity of dual drug-loaded transfersomes was studied in FaDu oral cancer cells. Results showed that the average particle size, polydispersity index, and zeta potential were 91±6.4 nm, 0.28±0.03, and (-)46.9±9.5 mV, respectively, for 5FU- and Et (1:1)-loaded transfersomes. The highest encapsulation efficiency achieved was 36.9±3.8% and 79.8±6.4% for 5FU and Et (1:1), respectively. Growth inhibition studies in FaDu cells using different concentrations of 5FU and Et showed a combination index of 0.36, indicating a synergistic effect. The FaDu cell uptake of drug-loaded transfersomes was significantly (p<0.05) greater than that of free drugs. The transfersome hydrogel made of HPMC (2% w/w) showed similar flux, lag time, and permeation coefficient as that of drug-loaded transfersomes across excised porcine buccal tissue. In conclusion, 5FU and Et transfersome hydrogel can be developed for localized delivery to treat oral cancer.
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12
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Exploring the potential of site-specific co-delivery of Berberine alongside 5-fluorouracil in oral cancer: Formulation development, in-vitro apoptosis, ex-vivo permeability and in-vivo biocompatibility studies. J Drug Deliv Sci Technol 2022. [DOI: 10.1016/j.jddst.2022.103105] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
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13
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Chen W, Jiang L, Hu Y, Fang G, Yang B, Li J, Liang N, Wu L, Hussain Z. Nanomedicines, an emerging therapeutic regimen for treatment of ischemic cerebral stroke: A review. J Control Release 2021; 340:342-360. [PMID: 34695522 DOI: 10.1016/j.jconrel.2021.10.020] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2021] [Revised: 10/14/2021] [Accepted: 10/15/2021] [Indexed: 12/18/2022]
Abstract
Owing to its intricate pathophysiology, cerebral stroke is a serious medical condition caused by interruption or obstruction of blood supply (blockage of vasculature) to the brain tissues which results in diminished supply of essential nutrients and oxygen (hypoxia) and ultimate necrosis of neuronal tissues. A prompt risks assessment and immediate rational therapeutic plan with proficient neuroprotection play critically important role in the effective management of this neuronal emergency. Various conventional medications are being used for treatment of acute ischemic cerebral stroke but fibrinolytic agents, alone or in combination with other agents are considered the mainstay. These clot-busting agents effectively restore blood supply (reperfusion) to ischemic regions of the brain; however, their clinical significance is hampered due to various factors such as short plasma half-life, limited distribution to brain tissues due to the presence of highly efficient physiological barrier, blood brain barrier (BBB), and lacking of target-specific delivery to the ischemic brain regions. To alleviate these issues, various types of nanomedicines such as polymeric nanoparticles (NPs), liposomes, nanoemulsion, micelles and dendrimers have been designed and evaluated. The implication of these newer therapies (nanomedicines) have revolutionized the therapeutic outcomes by improving the plasma half-life, permeation across BBB, efficient distribution to ischemic cerebral tissues and neuroprotection. Furthermore, the adaptation of some diverse techniques including PEGylation, tethering of targeting ligands on the surfaces of nanomedicines, and pH responsive features have also been pondered. The implication of these emerging adaptations have shown remarkable potential in maximizing the targeting efficiency of drugs to ischemic brain tissues, simultaneous delivery of drugs and imaging agents (for early prognosis as well as monitoring of therapy), and therapeutic outcomes such as long-term neuroprotection.
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Affiliation(s)
- Wei Chen
- Department of Neurology, The First Affiliated Hospital of Guangxi, University of Chinese Medicine, Nanning, Guangxi 530023, China; Graduate School, Jiangxi University of Chinese Medicine, Nanchang, Jiangxi 330004, China
| | - Lingfei Jiang
- Graduate College, Guangxi University of Chinese Medicine, Nanning, Guangxi 530200, China
| | - Yueqiang Hu
- Department of Neurology, The First Affiliated Hospital of Guangxi, University of Chinese Medicine, Nanning, Guangxi 530023, China; Guangxi Key Laboratory of Chinese Medicine Foundation Research, Guangxi University of Chinese Medicine, Nanning, Guangxi 530200, China.
| | - Gang Fang
- Guangxi Zhuang and Yao Medicine Engineering Technology Research Center, Guangxi University of Chinese Medicine, Nanning, Guangxi 530200, China
| | - Bilin Yang
- Graduate College, Guangxi University of Chinese Medicine, Nanning, Guangxi 530200, China
| | - Junhong Li
- Department of Neurology, The First Affiliated Hospital of Guangxi, University of Chinese Medicine, Nanning, Guangxi 530023, China
| | - Ni Liang
- Department of Neurology, The First Affiliated Hospital of Guangxi, University of Chinese Medicine, Nanning, Guangxi 530023, China
| | - Lin Wu
- Department of Neurology, The First Affiliated Hospital of Guangxi, University of Chinese Medicine, Nanning, Guangxi 530023, China; Guangxi Key Laboratory of Chinese Medicine Foundation Research, Guangxi University of Chinese Medicine, Nanning, Guangxi 530200, China.
| | - Zahid Hussain
- Department of Pharmaceutics and Pharmaceutical Technology, College of Pharmacy, University of Sharjah, Sharjah 27272, United Arab Emirates; Research Institute for Medical & Health Sciences, University of Sharjah, Sharjah 27272, United Arab Emirates.
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14
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Nanoparticles in Dentistry: A Comprehensive Review. Pharmaceuticals (Basel) 2021; 14:ph14080752. [PMID: 34451849 PMCID: PMC8398506 DOI: 10.3390/ph14080752] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2021] [Revised: 07/20/2021] [Accepted: 07/28/2021] [Indexed: 02/07/2023] Open
Abstract
In recent years, nanoparticles (NPs) have been receiving more attention in dentistry. Their advantageous physicochemical and biological properties can improve the diagnosis, prevention, and treatment of numerous oral diseases, including dental caries, periodontal diseases, pulp and periapical lesions, oral candidiasis, denture stomatitis, hyposalivation, and head, neck, and oral cancer. NPs can also enhance the mechanical and microbiological properties of dental prostheses and implants and can be used to improve drug delivery through the oral mucosa. This paper reviewed studies from 2015 to 2020 and summarized the potential applications of different types of NPs in the many fields of dentistry.
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15
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Fu Y, Saraswat A, Wei Z, Agrawal MY, Dukhande VV, Reznik SE, Patel K. Development of Dual ARV-825 and Nintedanib-Loaded PEGylated Nano-Liposomes for Synergistic Efficacy in Vemurafnib-Resistant Melanoma. Pharmaceutics 2021; 13:pharmaceutics13071005. [PMID: 34371697 PMCID: PMC8308940 DOI: 10.3390/pharmaceutics13071005] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2021] [Revised: 06/21/2021] [Accepted: 06/25/2021] [Indexed: 12/21/2022] Open
Abstract
A novel treatment strategy by co-targeting c-Myc and tumor stroma was explored in vemurafenib-resistant melanoma. BRD4 proteolysis targeting chimera (ARV-825) and nintedanib co-loaded PEGylated nanoliposomes (ARNIPL) were developed to incorporate a synergistic cytotoxic ratio. Both the molecules have extremely poor aqueous solubility. A modified hydration method with citric acid was used to improve the loading of both the molecules in liposomes. ARNIPL with mean particle size 111.1 ± 6.55 nm exhibited more than 90% encapsulation efficiency for both the drugs and was found to be physically stable for a month at 4 °C. Both the molecules and ARNIPL showed significantly higher cytotoxicity, apoptosis and down-regulation of target proteins BRD4 and c-Myc in vemurafenib-resistant cell line (A375R). Vasculogenic mimicry and clonogenic potential of A375R were significantly inhibited by ARNIPL. Tumor growth inhibition in 3D spheroids with reduction of TGF-β1 was observed with ARNIPL treatment. Therefore, ARNIPL could be a promising therapeutic approach for the treatment of vemurafenib-resistant melanoma.
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16
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Zheng W, Zhou Q, Yuan C. Nanoparticles for Oral Cancer Diagnosis and Therapy. Bioinorg Chem Appl 2021; 2021:9977131. [PMID: 33981334 PMCID: PMC8088384 DOI: 10.1155/2021/9977131] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2021] [Revised: 04/04/2021] [Accepted: 04/07/2021] [Indexed: 02/06/2023] Open
Abstract
Oral cancer is the sixth most common malignant cancer, affecting the health of people with an unacceptably high mortality rate. Despite numerous clinical methods in the diagnosis and therapy of oral cancer (e.g., magnetic resonance imaging, computed tomography, surgery, and chemoradiotherapy), they still remain far from optimal. Therefore, an urgent need exists for effective and practical techniques of early diagnosis and effective therapy of oral cancer. Currently, various types of nanoparticles have aroused wide public concern, representing a promising tool for diagnostic probes and therapeutic devices. Their inherent physicochemical features, including ultrasmall size, high reactivity, and tunable surface modification, enable them to overcome some of the limitations and achieve the expected diagnostic and therapeutic effect. In this review, we introduce different types of nanoparticles that emerged for the diagnosis and therapy of oral cancers. Then, the challenges and future perspectives for nanoparticles applied in oral cancer diagnosis and therapy are presented. The objective of this review is to help researchers better understand the effect of nanoparticles on oral cancer diagnosis and therapy and may accelerate breakthroughs in this field.
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Affiliation(s)
- Weiping Zheng
- Department of Stomatology, The Affiliated Hospital of Qingdao University, Qingdao 266003, China
- School of Stomatology, Qingdao University, Qingdao 266003, China
| | - Qihui Zhou
- Department of Stomatology, The Affiliated Hospital of Qingdao University, Qingdao 266003, China
- School of Stomatology, Qingdao University, Qingdao 266003, China
- Institute for Translational Medicine, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao 266021, China
| | - Changqing Yuan
- Department of Stomatology, The Affiliated Hospital of Qingdao University, Qingdao 266003, China
- School of Stomatology, Qingdao University, Qingdao 266003, China
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17
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Xing L, Zheng Y, Yu Y, Wu R, Liu X, Zhou R, Huang Y. Complying with the physiological functions of Golgi apparatus for secretory exocytosis facilitated oral absorption of protein drugs. J Mater Chem B 2021; 9:1707-1718. [PMID: 33496710 DOI: 10.1039/d0tb02848g] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
Intestinal epithelial cells are the primary biological barriers for orally administrated nano-formulations and the delivered protein drugs. Thereinto, besides the cellular uptake, intracellular trafficking pathway and the related exocytosis are of great importance to the trans-epithelial transport of drug-loaded NPs. Herein, inspired by the physiological functions of Golgi apparatus for secreting proteins out of cells, Golgi localization-related amino acid l-cysteine (Cys) was modified on the surface of NPs to see whether and how this modification could guide the Golgi pathway-related transport and facilitate the exocytosis of drug-loaded NPs. Meanwhile, cell-penetrating peptide octa-arginine (R8) was co-modified to increase the cellular uptake. The proportion of R8 and Cys modification was explored to get the best effect of endocytosis and exocytosis of NPs. As a result, 25%R8 + 75%Cys NPs with most Cys modification showed efficient transcytosis with the highest transcytosis/endocytosis ratio (0.87). Interestingly, exocytosis mechanism studies indicated that they trafficked through the Golgi secretory pathway and bypassed lysosomes due to Cys modification. The detailed Golgi position mechanism studies further suggested that the thiol group from Cys was important for mediating Golgi transport. In particular, competitive inhibition studies demonstrated that Cys-modified NPs were more conducive to their exocytosis after being transported through the Golgi secretory pathway. We proved that cargos transported via Golgi apparatus tended to be trafficked out of the cells and avoid degradation, which contributed to the transcytosis of 25%R8 + 75%Cys NPs in vitro. Inspiringly, compared with unmodified NPs, 25%R8 + 75%Cys NPs also exhibited promoted intestinal penetration and oral absorption in vivo. Oral delivery of insulin-loaded 25%R8 + 75%Cys NPs showed stronger hypoglycemic effects in diabetic rats. In summary, this work provides a strategy for complying with the physiological functions of Golgi apparatus for secreting to facilitate the exocytosis of NPs, thus further improving the oral absorption of loaded protein drugs.
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Affiliation(s)
- Liyun Xing
- Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
| | - Yaxian Zheng
- Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
| | - Yinglan Yu
- Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
| | - Ruinan Wu
- Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
| | - Xi Liu
- Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
| | - Rui Zhou
- Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
| | - Yuan Huang
- Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
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18
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Sarmah D, Banerjee M, Datta A, Kalia K, Dhar S, Yavagal DR, Bhattacharya P. Nanotechnology in the diagnosis and treatment of stroke. Drug Discov Today 2021; 26:585-592. [PMID: 33242696 DOI: 10.1016/j.drudis.2020.11.018] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2020] [Revised: 11/05/2020] [Accepted: 11/16/2020] [Indexed: 01/28/2023]
Abstract
Increasing developments in the field of nanotechnology have ignited its use in stroke diagnosis and treatment. The benefits of structural modification, ease of synthesis, and biocompatibility support the use of nanomaterials in the clinic. The pathophysiology of stroke is complex, involving different brain regions; hence, therapeutic agents are required to be delivered to specific regions. Nanoparticles (NPs) can be engineered to help improve the delivery and release of therapeutic agents in a localized manner, especially in the penumbra. This contributes not only to therapy, but also to neurosurgery and neuroimaging. Nanomaterials also offer high efficacy with few adverse effects. In this review, we provide a concise summary of the caveats associated with nanotechnology with respect to stroke therapy and diagnosis.
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Affiliation(s)
- Deepaneeta Sarmah
- Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Ahmedabad, Gandhinagar, Gujarat 382355, India
| | - Mainak Banerjee
- Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, Miami, FL, USA
| | - Aishika Datta
- Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Ahmedabad, Gandhinagar, Gujarat 382355, India
| | - Kiran Kalia
- Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Ahmedabad, Gandhinagar, Gujarat 382355, India
| | - Shanta Dhar
- Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, Miami, FL, USA; Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL, USA
| | - Dileep R Yavagal
- Department of Neurology and Neurosurgery, University of Miami Miller School of Medicine, Miami, FL, USA
| | - Pallab Bhattacharya
- Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Ahmedabad, Gandhinagar, Gujarat 382355, India.
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19
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Almalki WH, Alghamdi S, Alzahrani A, Zhang W. Emerging paradigms in treating cerebral infarction with nanotheranostics: opportunities and clinical challenges. Drug Discov Today 2020; 26:826-835. [PMID: 33383212 DOI: 10.1016/j.drudis.2020.12.018] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2020] [Revised: 10/10/2020] [Accepted: 12/21/2020] [Indexed: 12/28/2022]
Abstract
Interest is increasing in the use of nanotheranostics as diagnosis, imaging and therapeutic tools for stroke management, but movement to the clinic remains challenging.
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Affiliation(s)
- Waleed H Almalki
- Department of Pharmacology and Toxicology, College of Pharmacy, Umm al-qura University, Saudi Arabia.
| | - Saad Alghamdi
- Laboratory Medicine Department, Faculty of Applied Medical Sciences, Umm Al-qura University, Makkah, Saudi Arabia
| | - Abdulaziz Alzahrani
- Department of Pharmacology, College of Clinical Pharmacy, Albaha University, Saudi Arabia
| | - Wenzhi Zhang
- Senior Research Scientist, Inn Research Sdn. Bhd., Subang Jaya, Selangor, Malaysia
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20
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Zhao Z, Li D, Wu Z, Wang Q, Ma Z, Zhang C. Research Progress and Prospect of Nanoplatforms for Treatment of Oral Cancer. Front Pharmacol 2020; 11:616101. [PMID: 33391000 PMCID: PMC7773899 DOI: 10.3389/fphar.2020.616101] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2020] [Accepted: 11/30/2020] [Indexed: 12/27/2022] Open
Abstract
Oral cancers refer to malignant tumors associated with high morbidity and mortality, and oral squamous cell carcinoma accounts for the majority of cases. It is an important part of head and neck, and oral cancer is one of the six most common cancers in the world. At present, the traditional treatment methods for oral cancer include surgery, radiation therapy, and chemotherapy. However, these methods have many disadvantages. In recent years, nanomedicine, the delivery of drugs through nanoplatforms for the treatment of cancer, has become a promising substitutive therapy. The use of nanoplatforms can reduce the degradation of the drug in the body and accurately deliver it to the tumor site. This minimizes the distribution of the drug to other organs, thereby reducing its toxicity and allowing higher drug concentration at the tumor site. This review introduces polymer nanoparticles, lipid-based nanoparticles, metal nanoparticles, hydrogels, exosomes, and dendrimers for the treatment of oral cancer, and discusses how these nanoplatforms play an anti-cancer effect. Finally, the review gives a slight outlook on the future prospects of nanoplatforms for oral cancer treatment.
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Affiliation(s)
- Zhilong Zhao
- Department of Stomatology, The First Hospital of Jilin University, Changchun, China
| | - Dan Li
- Department of Cancer Center, The First Hospital of Jilin University, Changchun, China
| | - Ziqi Wu
- Department of Stomatology, The First Hospital of Jilin University, Changchun, China
| | - Qihui Wang
- Department of Stomatology, The First Hospital of Jilin University, Changchun, China
| | | | - Congxiao Zhang
- Department of Stomatology, The First Hospital of Jilin University, Changchun, China
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21
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Aguilar-Pérez KM, Avilés-Castrillo JI, Medina DI, Parra-Saldivar R, Iqbal HMN. Insight Into Nanoliposomes as Smart Nanocarriers for Greening the Twenty-First Century Biomedical Settings. Front Bioeng Biotechnol 2020; 8:579536. [PMID: 33384988 PMCID: PMC7770187 DOI: 10.3389/fbioe.2020.579536] [Citation(s) in RCA: 75] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2020] [Accepted: 11/24/2020] [Indexed: 02/05/2023] Open
Abstract
The necessity to develop more efficient, biocompatible, patient compliance, and safer treatments in biomedical settings is receiving special attention using nanotechnology as a potential platform to design new drug delivery systems (DDS). Despite the broad range of nanocarrier systems in drug delivery, lack of biocompatibility, poor penetration, low entrapment efficiency, and toxicity are significant challenges that remain to address. Such practices are even more demanding when bioactive agents are intended to be loaded on a nanocarrier system, especially for topical treatment purposes. For the aforesaid reasons, the search for more efficient nano-vesicular systems, such as nanoliposomes, with a high biocompatibility index and controlled releases has increased considerably in the past few decades. Owing to the stratum corneum layer barrier of the skin, the in-practice conventional/conformist drug delivery methods are inefficient, and the effect of the administered therapeutic cues is limited. The current advancement at the nanoscale has transformed the drug delivery sector. Nanoliposomes, as robust nanocarriers, are becoming popular for biomedical applications because of safety, patient compliance, and quick action. Herein, we reviewed state-of-the-art nanoliposomes as a smart and sophisticated drug delivery approach. Following a brief introduction, the drug delivery mechanism of nanoliposomes is discussed with suitable examples for the treatment of numerous diseases with a brief emphasis on fungal infections. The latter half of the work is focused on the applied perspective and clinical translation of nanoliposomes. Furthermore, a detailed overview of clinical applications and future perspectives has been included in this review.
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Affiliation(s)
| | | | | | | | - Hafiz M. N. Iqbal
- Tecnologico de Monterrey, School of Engineering and Sciences, Monterrey, Mexico
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22
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Zhang M, Chen X, Radacsi N. New tricks of old drugs: Repurposing non-chemo drugs and dietary phytochemicals as adjuvants in anti-tumor therapies. J Control Release 2020; 329:96-120. [PMID: 33259852 DOI: 10.1016/j.jconrel.2020.11.047] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2020] [Revised: 11/22/2020] [Accepted: 11/24/2020] [Indexed: 12/14/2022]
Abstract
Combination therapy has long been applied to enhance therapeutic effect and deal with the occurrence of multi-drug resistance in cancer treatment. However, the overlapping toxicity of multiple anticancer drugs to healthy tissues and increasing financial burden on patients emerged as major concerns. As promising alternatives to chemo agents, repurposed non-chemo drugs and dietary phytochemicals have been investigated as adjuvants to conventional anti-tumor therapeutics, offering a safe and economic strategy for combination therapy. In this review, we aim to highlight the advances in research about combination therapy using conventional therapeutics and repurposed drugs or phytochemicals for an enhanced anti-tumor efficacy, along with the mechanisms involved in the synergism. Beyond these, we outlined the potential challenges and solutions for clinical translation of the proposed combination therapy, providing a safe and affordable strategy to improve the reach of cancer therapy to low income regions with such new tricks of old drugs.
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Affiliation(s)
- Mei Zhang
- School of Engineering, Institute for Materials and Processes, University of Edinburgh, Robert Stevenson Road, Edinburgh EH9 3FB, United Kingdom; School of Engineering, Institute for Bioengineering, University of Edinburgh, The King's Buildings, Edinburgh EH9 3JL, United Kingdom.
| | - Xianfeng Chen
- School of Engineering, Institute for Bioengineering, University of Edinburgh, The King's Buildings, Edinburgh EH9 3JL, United Kingdom.
| | - Norbert Radacsi
- School of Engineering, Institute for Materials and Processes, University of Edinburgh, Robert Stevenson Road, Edinburgh EH9 3FB, United Kingdom.
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23
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Fu Y, Rathod D, Patel K. Protein kinase C inhibitor anchored BRD4 PROTAC PEGylated nanoliposomes for the treatment of vemurafenib-resistant melanoma. Exp Cell Res 2020; 396:112275. [PMID: 32898554 PMCID: PMC12045034 DOI: 10.1016/j.yexcr.2020.112275] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2020] [Revised: 09/03/2020] [Accepted: 09/04/2020] [Indexed: 12/11/2022]
Abstract
Limited treatment options and development of resistance to targeted therapy within few months pose significant challenges in the treatment of BRAF-mutated malignant melanoma. Moreover, extensive angiogenesis and vasculogenic mimicry promote the rapid progression of disease. The purpose of this study was to develop a protein kinase C inhibitor anchored BRD4 PROTAC (ARV) loaded PEGylated nanoliposomes (LARPC). Palmitoyl-dl-carnitine chloride (PC) was used as a protein kinase C inhibitor to provide a cationic surface charge to LARPC. The formulation was characterized for particle size, zeta potential, drug release and various cell culture assays using HUVEC and vemurafenib resistant melanoma cells. The particle size of LARPC was found to be 105.25 ± 2.76 nm with a zeta potential of +26.6 ± 6.25 mV. Inhibition of angiogenesis was demonstrated by ARV and LARPC using human umbilical vein endothelial cells (HUVEC)-based matrigel basement membrane model. Additionally, LARPC demonstrated very low IC50 with promising inhibition of vasculogenic mimicry channel formation, cell migration as well as colony formation in vemurafenib-resistant melanoma cell lines. Hence, the outcome of this combination therapy indicated the suitability of LARPC as a potential and novel approach for eradicating vemurafenib-resistant melanoma.
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Affiliation(s)
- Yige Fu
- College of Pharmacy and Health Sciences, St. John's University, Queens, NY, 11439, USA
| | - Drishti Rathod
- College of Pharmacy and Health Sciences, St. John's University, Queens, NY, 11439, USA
| | - Ketan Patel
- College of Pharmacy and Health Sciences, St. John's University, Queens, NY, 11439, USA.
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Ding Q, Cui J, Shen H, He C, Wang X, Shen SGF, Lin K. Advances of nanomaterial applications in oral and maxillofacial tissue regeneration and disease treatment. WILEY INTERDISCIPLINARY REVIEWS. NANOMEDICINE AND NANOBIOTECHNOLOGY 2020; 13:e1669. [PMID: 33090719 DOI: 10.1002/wnan.1669] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/23/2020] [Revised: 07/20/2020] [Accepted: 08/01/2020] [Indexed: 12/13/2022]
Abstract
Using bioactive nanomaterials in clinical treatment has been widely aroused. Nanomaterials provide substantial improvements in the prevention and treatment of oral and maxillofacial diseases. This review aims to discuss new progresses in nanomaterials applied to oral and maxillofacial tissue regeneration and disease treatment, focusing on the use of nanomaterials in improving the quality of oral and maxillofacial healthcare, and discuss the perspectives of research in this arena. Details are provided on the tissue regeneration, wound healing, angiogenesis, remineralization, antitumor, and antibacterial regulation properties of nanomaterials including polymers, micelles, dendrimers, liposomes, nanocapsules, nanoparticles and nanostructured scaffolds, etc. Clinical applications of nanomaterials as nanocomposites, dental implants, mouthwashes, biomimetic dental materials, and factors that may interact with nanomaterials behaviors and bioactivities in oral cavity are addressed as well. In the last section, the clinical safety concerns of their usage as dental materials are updated, and the key knowledge gaps for future research with some recommendation are discussed. This article is categorized under: Implantable Materials and Surgical Technologies > Nanomaterials and Implants Implantable Materials and Surgical Technologies > Nanotechnology in Tissue Repair and Replacement.
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Affiliation(s)
- Qinfeng Ding
- Department of Oral and Cranio-Maxillofacial Surgery, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- National Clinical Research Center for Oral Diseases, Shanghai, China
- Shanghai Key Laboratory of Stomatology and Shanghai Research Institute of Stomatology, Shanghai, China
| | - Jinjie Cui
- Department of Oral and Cranio-Maxillofacial Surgery, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- National Clinical Research Center for Oral Diseases, Shanghai, China
- Shanghai Key Laboratory of Stomatology and Shanghai Research Institute of Stomatology, Shanghai, China
| | - Hangqi Shen
- Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai, China
- Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai, China
| | - Chuanglong He
- College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai, China
| | - Xudong Wang
- Department of Oral and Cranio-Maxillofacial Surgery, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- National Clinical Research Center for Oral Diseases, Shanghai, China
- Shanghai Key Laboratory of Stomatology and Shanghai Research Institute of Stomatology, Shanghai, China
| | - Steve G F Shen
- Department of Oral and Cranio-Maxillofacial Surgery, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- National Clinical Research Center for Oral Diseases, Shanghai, China
- Shanghai Key Laboratory of Stomatology and Shanghai Research Institute of Stomatology, Shanghai, China
- Shanghai University of Medicine and Health Sciences, Shanghai, China
| | - Kaili Lin
- Department of Oral and Cranio-Maxillofacial Surgery, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- National Clinical Research Center for Oral Diseases, Shanghai, China
- Shanghai Key Laboratory of Stomatology and Shanghai Research Institute of Stomatology, Shanghai, China
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Xu Q, Fang M, Zhu J, Dong H, Cao J, Yan L, Leonard F, Oppel F, Sudhoff H, Kaufmann AM, Albers AE, Qian X. Insights into Nanomedicine for Immunotherapeutics in Squamous Cell Carcinoma of the head and neck. Int J Biol Sci 2020; 16:2506-2517. [PMID: 32792853 PMCID: PMC7415431 DOI: 10.7150/ijbs.47068] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2020] [Accepted: 07/01/2020] [Indexed: 02/06/2023] Open
Abstract
Immunotherapies such as immune checkpoint blockade benefit only a portion of patients with head and neck squamous cell carcinoma. The multidisciplinary field of nanomedicine is emerging as a promising strategy to achieve maximal anti-tumor effect in cancer immunotherapy and to turn non-responders into responders. Various methods have been developed to deliver therapeutic agents that can overcome bio-barriers, improve therapeutic delivery into the tumor and lymphoid tissues and reduce adverse effects in normal tissues. Additional modification strategies also have been employed to improve targeting and boost cytotoxic T cell-based immune responses. Here, we review the state-of-the-art use of nanotechnologies in the laboratory, in advanced preclinical phases as well as those running through clinical trials assessing their advantages and challenges.
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Affiliation(s)
- Qiang Xu
- Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital); Institute of Cancer and Basic Medicine (IBMC), Chinese Academy of Sciences. Hangzhou, P.R. China
| | - Meiyu Fang
- Key Laboratory of Head & Neck Cancer Translational Research of Zhejiang Province, Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital); Institute of Cancer and Basic Medicine (IBMC), Chinese Academy of Sciences. Hangzhou, P.R. China
| | - Jing Zhu
- Department of Clinical Laboratory, Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital); Institute of Cancer and Basic Medicine (IBMC), Chinese Academy of Sciences. Hangzhou, P.R. China
| | - Haoru Dong
- First School of Clinical Medicine, Wenzhou Medical University, Wenzhou, P.R. China
| | - Jun Cao
- Key Laboratory of Head & Neck Cancer Translational Research of Zhejiang Province, Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital); Institute of Cancer and Basic Medicine (IBMC), Chinese Academy of Sciences. Hangzhou, P.R. China
| | - Lin Yan
- Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, P.R. China
| | - Fransisca Leonard
- Department of Nanomedicine, Houston Methodist Research Institute, Houston, USA
| | - Felix Oppel
- Department of Otolaryngology, Head and Neck Surgery, Klinikum Bielefeld, Bielefeld, Germany
| | - Holger Sudhoff
- Department of Otolaryngology, Head and Neck Surgery, Klinikum Bielefeld, Bielefeld, Germany
| | - Andreas M Kaufmann
- Clinic for Gynecology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
| | - Andreas E Albers
- Department of Otolaryngology, Head and Neck Surgery, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
| | - Xu Qian
- Department of Clinical Laboratory, Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital); Institute of Cancer and Basic Medicine (IBMC), Chinese Academy of Sciences. Hangzhou, P.R. China
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Wine Consumption and Oral Cavity Cancer: Friend or Foe, Two Faces of Janus. Molecules 2020; 25:molecules25112569. [PMID: 32486484 PMCID: PMC7321235 DOI: 10.3390/molecules25112569] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2020] [Revised: 05/21/2020] [Accepted: 05/28/2020] [Indexed: 12/29/2022] Open
Abstract
The health benefits of moderate wine consumption have been extensively studied during the last few decades. Some studies have demonstrated protective associations between moderate drinking and several diseases including oral cavity cancer (OCC). However, due to the various adverse effects related to ethanol content, the recommendation of moderate wine consumption has been controversial. The polyphenolic components of wine contribute to its beneficial effects with different biological pathways, including antioxidant, lipid regulating and anti-inflammatory effects. On the other hand, in the oral cavity, ethanol is oxidized to form acetaldehyde, a metabolite with genotoxic properties. This review is a critical compilation of both the beneficial and the detrimental effects of wine consumption on OCC.
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Zhang J, Li X, Huang L. Anticancer activities of phytoconstituents and their liposomal targeting strategies against tumor cells and the microenvironment. Adv Drug Deliv Rev 2020; 154-155:245-273. [PMID: 32473991 PMCID: PMC7704676 DOI: 10.1016/j.addr.2020.05.006] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2020] [Revised: 05/07/2020] [Accepted: 05/20/2020] [Indexed: 12/13/2022]
Abstract
Various bioactive ingredients have been extracted from Chinese herbal medicines (CHMs) that affect tumor progression and metastasis. To further understand the mechanisms of CHMs in cancer therapy, this article summarizes the effects of five categories of CHMs and their active ingredients on tumor cells and the tumor microenvironment. Despite their treatment potential, the undesirable physicochemical properties (poor permeability, instability, high hydrophilicity or hydrophobicity, toxicity) and unwanted pharmacokinetic profiles (short half-life in blood and low bioavailability) restrict clinical studies of CHMs. Therefore, development of liposomes through relevant surface modifying techniques to achieve targeted CHM delivery for cancer cells, i.e., extracellular and intracellular targets and targets in tumor microenvironment or vasculature, have been reviewed. Current challenges of liposomal targeting of these phytoconstituents and future perspective of CHM applications are discussed to provide an informative reference for interested readers.
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Affiliation(s)
- Jing Zhang
- Key Laboratory of Modern Preparation of TCM, Ministry of Education, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, Jiangxi, China
| | - Xiang Li
- Key Laboratory of Modern Preparation of TCM, Ministry of Education, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, Jiangxi, China
| | - Leaf Huang
- Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, United States.
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Patel P, Meghani N, Kansara K, Kumar A. Nanotherapeutics for the Treatment of Cancer and Arthritis. Curr Drug Metab 2020; 20:430-445. [PMID: 30479211 DOI: 10.2174/1389200220666181127102720] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2018] [Revised: 10/11/2018] [Accepted: 10/11/2018] [Indexed: 02/06/2023]
Abstract
BACKGROUND Nanotechnology is gaining significant attention worldwide for the treatment of complex diseases such as AIDS (acquired immune deficiency syndrome), cancer and rheumatoid arthritis. Nanomedicine is the application of nanotechnology used for diagnosis and treatment for the disease that includes the preservation and improvement of human health by covering an area such as drug delivery using nanocarriers, nanotheranostics and nanovaccinology. The present article provides an insight into several aspects of nanomedicine such as usages of multiple types of nanocarriers, their status, advantages and disadvantages with reference to cancer and rheumatoid arthritis. METHODS An extensive search was performed on the bibliographic database for research article on nanotechnology and nanomedicine along with looking deeply into the aspects of these diseases, and how all of them are co-related. We further combined all the necessary information from various published articles and briefed to provide the current status. RESULTS Nanomedicine confers a unique technology against complex diseases which includes early diagnosis, prevention, and personalized therapy. The most common nanocarriers used globally are liposomes, polymeric nanoparticles, dendrimers, metallic nanoparticles, magnetic nanoparticles, solid lipid nanoparticles, polymeric micelles and nanotubes among others. CONCLUSION Nanocarriers are used to deliver drugs and biomolecules like proteins, antibody fragments, DNA fragments, and RNA fragments as the base of cancer biomarkers.
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Affiliation(s)
- Pal Patel
- Biological and Life Sciences, School of Arts and Sciences, Ahmedabad University, Central Campus, Navrangpura, Ahmedabad, 380009, Gujarat, India
| | - Nikita Meghani
- Biological and Life Sciences, School of Arts and Sciences, Ahmedabad University, Central Campus, Navrangpura, Ahmedabad, 380009, Gujarat, India
| | - Krupa Kansara
- Biological and Life Sciences, School of Arts and Sciences, Ahmedabad University, Central Campus, Navrangpura, Ahmedabad, 380009, Gujarat, India
| | - Ashutosh Kumar
- Biological and Life Sciences, School of Arts and Sciences, Ahmedabad University, Central Campus, Navrangpura, Ahmedabad, 380009, Gujarat, India
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Liposome Delivery of Natural STAT3 Inhibitors for the Treatment of Cancer. PHARMACEUTICAL FRONTIERS 2019; 1. [PMID: 31886474 DOI: 10.20900/pf20190007] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
In the tumor microenvironment, cytokines, growth factors, and oncogenes mediate constitutive activation of the signal transducer and activator of transcription 3 (STAT3) signaling pathway in both cancer cells and infiltrating immune cells. STAT3 activation in cancer cells drives tumorigenic changes that allow for increased survival, proliferation, and resistance to apoptosis. The modulation of immune cells is more complicated and conflicting. STAT3 signaling drives the myeloid cell phenotype towards an immune suppressive state, which mediates T cell inhibition. On the other hand, STAT3 signaling in T cells leads to proliferation and T cell activity required for an anti-tumor response. Targeted delivery of STAT3 inhibitors to cancer cells and myeloid cells could therefore improve therapeutic outcomes. Many compounds that inhibit the STAT3 pathways for cancer treatment include peptide drugs, small molecule inhibitors, and natural compounds. However, natural compounds that inhibit STAT3 are often hydrophobic, which reduces their bioavailability and leads to unfavorable pharmacokinetics. This review focuses specifically on liposome-encapsulated natural STAT3 inhibitors and their ability to target cancer cells and myeloid cells to reduce tumor growth and decrease STAT3-mediated immune suppression. Many of these liposome formulations have led to profound tumor reduction and examples of combination formulations have been shown to eliminate tumors through immune modulation.
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The Application of Nanotechnology in the Codelivery of Active Constituents of Plants and Chemotherapeutics for Overcoming Physiological Barriers during Antitumor Treatment. BIOMED RESEARCH INTERNATIONAL 2019; 2019:9083068. [PMID: 31915707 PMCID: PMC6930735 DOI: 10.1155/2019/9083068] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/11/2019] [Accepted: 11/27/2019] [Indexed: 12/17/2022]
Abstract
Antitumor therapy using a combination of drugs has shown increased clinical efficacy. Active constituents derived from plants can offer several advantages, such as high efficiacy, low toxicity, extensive effects, and multiple targets. At present, the combination of plants' active constituents and chemotherapeutic drugs has attracted increased attention. Nanodrug delivery systems (NDDSs) have been widely used in tumor-targeted therapy because of their efficacy of delivering antitumor drugs. The in vivo process of tumor-targeted NDDSs has several steps. They include blood circulation, tumor accumulation and penetration, target cell internalization and uptake, and drug release and drug response. In each step, NDDSs encounter multiple barriers that prevent their effective delivery to target sites. Studies have been performed to find alternative strategies to overcome these barriers. We reviewed the recent progress of codelivery of active constituents of plants and chemotherapeutics using NDDSs. Progress into transversing the physiological barriers for more effective in vivo antitumor delivery will be discussed in this review.
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Zhang WY, Du F, He M, Bai L, Gu YY, Yang LL, Liu YJ. Studies of anticancer activity in vitro and in vivo of iridium(III) polypyridyl complexes-loaded liposomes as drug delivery system. Eur J Med Chem 2019; 178:390-400. [DOI: 10.1016/j.ejmech.2019.06.009] [Citation(s) in RCA: 37] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2019] [Accepted: 06/03/2019] [Indexed: 12/25/2022]
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Roopmani P, Satheesh S, Raj DC, Krishnan UM. Development of Dual Drug Eluting Cardiovascular Stent with Ultrathin Flexible Poly(l-lactide- co-caprolactone) Coating. ACS Biomater Sci Eng 2019; 5:2899-2915. [PMID: 33405593 DOI: 10.1021/acsbiomaterials.9b00303] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
The pleiotropic effects of the atorvastatin-fenofibrate combination can be effectively harnessed for site-specific therapy to minimize stent-related complications. The present study aims to utilize the pleiotropic effects of these two drugs entrapped in a uniform and defect-free coating of poly(l-lactide-co-caprolactone) (PLCL) on a stainless steel stent to overcome stent-associated limitations. The stent coating parameters were optimized using ultrasonic spray coating technique to achieve a thin, smooth, and defect-free dual drug-loaded polymer coating on the stent. The dual drug-loaded polymer coated stent was characterized for surface morphology, thickness and coating integrity. In vitro drug release kinetics of the fabricated stent reveals a sustained release of both drugs for more than 60 days. Significant reduction of thrombus formation and adhesion of lipopolysaccharide-stimulated macrophages on the dual drug containing polymer-coated stent indicates that the drug combination possesses antithrombotic and anti-inflammatory effects. The combination did not adversely influence endothelialization but significantly retarded smooth muscle cell proliferation indicating its potential to overcome restenosis. No bacterial biofilm formation was observed on the stent due to the antibacterial activity of atorvastatin. A rat subcutaneous model was used to evaluate the biocompatibility of the coated stent and compared with the commercial stent. MicroCT, scanning electron microscopy, and morphometric analyses revealed that the coated stents exhibited excellent histocompatibility with no inflammatory response as evidenced from the cytokine levels measured 28 days postimplantation. Our data demonstrates for the first time that the combination of atorvastatin and fenofibrate can be successfully employed in cardiovascular stents to overcome the current limitations of conventional drug-eluting stents.
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Affiliation(s)
| | - Santhosh Satheesh
- Department of Cardiology, Jawaharlal Institute of Post Graduate Medical Education and Research (JIPMER), Pondicherry-605006, India
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Kaviarasi S, Yuba E, Harada A, Krishnan UM. Emerging paradigms in nanotechnology for imaging and treatment of cerebral ischemia. J Control Release 2019; 300:22-45. [DOI: 10.1016/j.jconrel.2019.02.031] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2019] [Revised: 02/20/2019] [Accepted: 02/21/2019] [Indexed: 02/07/2023]
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Zheng T, Feng H, Liu L, Peng J, Xiao H, Yu T, Zhou Z, Li Y, Zhang Y, Bai X, Zhao S, Shi Y, Chen Y. Enhanced antiproliferative effect of resveratrol in head and neck squamous cell carcinoma using GE11 peptide conjugated liposome. Int J Mol Med 2019; 43:1635-1642. [PMID: 30816515 PMCID: PMC6414163 DOI: 10.3892/ijmm.2019.4096] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2018] [Accepted: 01/22/2019] [Indexed: 01/01/2023] Open
Abstract
The present study describes the preparation of a dodecapeptide YHWYGYTPQNVI (GE11)‑conjugated liposome bound with polyethylene glycol to enhance the therapeutic effect of resveratrol (RSV) in head and neck cancer cells. The results indicated that (RSV)‑loaded GE11‑conjugated liposomes (RSV‑GL) exhibited a high entrapment efficiency of >95%, with an active drug loading level of 19.5% w/w. Release kinetics revealed that RSV was released in a slow and sustained manner from the RSV‑GL and RSV‑loaded liposome (RSV‑L) nanoparticulate systems. The epidermal growth factor receptor (EGFR)‑overexpressing squamous cell carcinoma HN cells specifically internalized GE11 surface‑conjugated liposome in a manner that was markedly increased compared with that of the non‑targeted carrier. Consistently, RSV‑GL exhibited a significantly increased cytotoxic effect compared with that of the non‑targeted nanoparticles. Notably, RSV‑GL induced significantly increased proportions of early (~60%) and late (~10%) apoptotic cells in head and neck cancer cell populations. To the best of our knowledge, the application and development of EGFR‑targeted peptide‑conjugated liposome system for RSV delivery has not been studied previously in the treatment of head and neck cancer. In addition, RSV‑GL exhibited the greatest antitumor efficacy compared with any other group. RSV‑GL exhibited a 2‑fold decrease in tumor volume compared with the free RSV and a 3‑fold decrease in volume compared with the control. Overall, the nanomedicine strategy described in the present study may potentially advance the chemotherapy‑based treatment of head and neck cancer, with promising applications in other EGFR‑overexpressing tumors.
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Affiliation(s)
- Tingting Zheng
- Shenzhen Key Laboratory for Drug Addiction and Medication Safety, Shenzhen Peking University-Hong Kong University of Science and Technology Medical Center, Shenzhen, Guangdong 510852
- Department of Ultrasound
- Sanming Project of Medicine in Shenzhen, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036
| | - Huanhuan Feng
- Harbin Institute of Technology Shenzhen Graduate School, Shenzhen, Guangdong 510852
| | - Li Liu
- Shenzhen Key Laboratory for Drug Addiction and Medication Safety, Shenzhen Peking University-Hong Kong University of Science and Technology Medical Center, Shenzhen, Guangdong 510852
- Department of Ultrasound
| | - Jiao Peng
- Department of Pharmacy, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036
| | - Haitao Xiao
- Department of Pharmacy, Health Science Center, Shenzhen University, Shenzhen, Guangdong 518060
| | - Tao Yu
- Shenzhen Key Laboratory for Neuronal Structural Biology, Shenzhen Peking University-Hong Kong University of Science and Technology Medical Center, Shenzhen, Guangdong 510852, P.R. China
| | - Ziqian Zhou
- Shenzhen Key Laboratory for Drug Addiction and Medication Safety, Shenzhen Peking University-Hong Kong University of Science and Technology Medical Center, Shenzhen, Guangdong 510852
- Department of Ultrasound
| | - Ying Li
- Department of Pharmacy, Health Science Center, Shenzhen University, Shenzhen, Guangdong 518060
| | - Yuseng Zhang
- Shenzhen Key Laboratory for Drug Addiction and Medication Safety, Shenzhen Peking University-Hong Kong University of Science and Technology Medical Center, Shenzhen, Guangdong 510852
- Department of Ultrasound
| | - Xiaohe Bai
- Shenzhen Key Laboratory for Drug Addiction and Medication Safety, Shenzhen Peking University-Hong Kong University of Science and Technology Medical Center, Shenzhen, Guangdong 510852
- Department of Ultrasound
| | - Simeng Zhao
- Shenzhen Key Laboratory for Drug Addiction and Medication Safety, Shenzhen Peking University-Hong Kong University of Science and Technology Medical Center, Shenzhen, Guangdong 510852
- Department of Ultrasound
| | - Yu Shi
- Shenzhen Key Laboratory for Drug Addiction and Medication Safety, Shenzhen Peking University-Hong Kong University of Science and Technology Medical Center, Shenzhen, Guangdong 510852
- Department of Ultrasound
- Sanming Project of Medicine in Shenzhen, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036
| | - Yun Chen
- Shenzhen Key Laboratory for Drug Addiction and Medication Safety, Shenzhen Peking University-Hong Kong University of Science and Technology Medical Center, Shenzhen, Guangdong 510852
- Department of Ultrasound
- Sanming Project of Medicine in Shenzhen, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036
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Alaa El-Din Y, Sabry D, Abdelrahman AH, Fathy S. Potential therapeutic effects of induced pluripotent stem cells on induced salivary gland cancer in experimental rats. Biotech Histochem 2018; 94:92-99. [PMID: 30338701 DOI: 10.1080/10520295.2018.1508747] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023] Open
Abstract
Salivary gland neoplasms exhibit complex histopathology in a variety of tumor types and treatment options depend largely on the stage of the cancer. Induced pluripotent stem cells (iPS) have been investigated for treating induced salivary gland cancer and for restoring salivary gland function. We investigated iPS treatment for salivary gland cancer both in vitro and in vivo. For our study in vitro, we re-programmed human skin fibroblasts to form iPS cells using a plasmid containing Oct4, Sox2, L-MYC and LIN28. For our study in vivo, we used 30 white male albino rats divided into the following groups of 10: group 1 (control): rats were injected with phosphate-buffered saline (PBS), group 2 induced squamous cell carcinoma (SCC): rat submandibular glands were injected with squamous carcinoma cells (SCC), group 3 (induced SCC/iPS): SCC treated rats treated with 5 × 106 iPS cells. Submandibular glands from rats of all groups were examined histologically and real time PCR was performed for amylase, and COX I and COX II gene expression. We confirmed that submandibular gland specimens included tumor tissue before starting treatment with iPS. iPS treated cases exhibited regeneration of salivary glands, although minor degenerative and vascularization changes remained. The acinar cells regained their proper organization, but continued to exhibit abnormal activity including hyperchromatism. iPS cells may be useful for treating salivary gland carcinomas.
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Affiliation(s)
| | - Dina Sabry
- b Medical Biochemistry and Molecular Biology Department , Faculty of Medicine, Cairo University , Cairo , Egypt
| | - Amal Hassan Abdelrahman
- b Medical Biochemistry and Molecular Biology Department , Faculty of Medicine, Cairo University , Cairo , Egypt
| | - Safa Fathy
- c Oral & Maxillofacial Pathology , Faculty of Dentistry, Cairo University , Cairo , Egypt
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Feng Y, Gao Y, Wang D, Xu Z, Sun W, Ren P. Autophagy Inhibitor (LY294002) and 5-fluorouracil (5-FU) Combination-Based Nanoliposome for Enhanced Efficacy Against Esophageal Squamous Cell Carcinoma. NANOSCALE RESEARCH LETTERS 2018; 13:325. [PMID: 30328537 PMCID: PMC6192941 DOI: 10.1186/s11671-018-2716-x] [Citation(s) in RCA: 53] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/15/2018] [Accepted: 09/11/2018] [Indexed: 05/25/2023]
Abstract
In this study, 5-fluorouracil (5-FU) and LY294002 (LY)-loaded PEGylated nanoliposome was prepared to target esophageal squamous cell carcinoma (ESCC). The particles were characterized in terms of physicochemical and biological parameters. The co-delivery of autophagy inhibitor and chemotherapeutic drug in a single carrier was successfully accomplished. The two components from 5-FU and LY-loaded PEGylated nanoliposome (FLNP) released in a controlled manner with LY relatively released faster compared to that of 5-FU. FLNP showed a receptor-mediated cellular uptake that will allow the gradual release of drug in the acidic environment. The cellular uptake of nanoparticles (NP) was further confirmed by FACS analysis. The combination of 5-FU and LY resulted in higher cytotoxic effect compared to that of individual drugs. Most importantly, FLNP exhibited a significantly higher anticancer effect in cancer cells compared to that of free cocktail combinations. The faster release of LY from FLNP leads to autophagy inhibition that improves the sensitivity of cancer cells towards 5-FU, resulting in more cell death. Consistently, FLNP induced a greater apoptosis (~ 48%) of cancer cells compared to that of any other groups. Western blot analysis clearly showed that 5-FU and LY individually increased the expression of caspase-3 and PARP, while as expected FLNP induced a remarkable expression of these protein markers indicating the superior anticancer effect. We believe that the programmed release of autophagy inhibitor and chemotherapeutic drug from a single nanocarrier will increase the prospect of anticancer therapy in ESCC.
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Affiliation(s)
- Ye Feng
- Department of Gastrointestinal Surgery, China-Japan Friendship Hospital of Jilin University, Changchun, Jilin, 130033 China
| | - Yongjian Gao
- Department of Gastrointestinal Surgery, China-Japan Friendship Hospital of Jilin University, Changchun, Jilin, 130033 China
| | - Dayu Wang
- Department of Gastrointestinal Surgery, China-Japan Friendship Hospital of Jilin University, Changchun, Jilin, 130033 China
| | - Zhonghang Xu
- Department of Gastrointestinal Surgery, China-Japan Friendship Hospital of Jilin University, Changchun, Jilin, 130033 China
| | - Weixuan Sun
- Department of Gastrointestinal Surgery, China-Japan Friendship Hospital of Jilin University, Changchun, Jilin, 130033 China
| | - Ping Ren
- Department of Thoracic Surgery, The First Hospital of Jilin University, Changchun, Jilin, 130033 China
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Borišev I, Mrđanovic J, Petrovic D, Seke M, Jović D, Srđenović B, Latinovic N, Djordjevic A. Nanoformulations of doxorubicin: how far have we come and where do we go from here? NANOTECHNOLOGY 2018; 29:332002. [PMID: 29798934 DOI: 10.1088/1361-6528/aac7dd] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/24/2023]
Abstract
Nanotechnology, focused on discovery and development of new pharmaceutical products is known as nanopharmacology, and one research area this branch is engaged in are nanopharmaceuticals. The importance of being nano has been particularly emphasized in scientific areas dealing with nanomedicine and nanopharmaceuticals. Nanopharmaceuticals, their routes of administration, obstacles and solutions concerning their improved application and enhanced efficacy have been briefly yet comprehensively described. Cancer is one of the leading causes of death worldwide and evergrowing number of scientific research on the topic only confirms that the needs have not been completed yet and that there is a wide platform for improvement. This is undoubtedly true for nanoformulations of an anticancer drug doxorubicin, where various nanocarrriers were given an important role to reduce the drug toxicity, while the efficacy of the drug was supposed to be retained or preferably enhanced. Therefore, we present an interdisciplinary comprehensive overview of interdisciplinary nature on nanopharmaceuticals based on doxorubicin and its nanoformulations with valuable information concerning trends, obstacles and prospective of nanopharmaceuticals development, mode of activity of sole drug doxorubicin and its nanoformulations based on different nanocarriers, their brief descriptions of biological activity through assessing in vitro and in vivo behavior.
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Affiliation(s)
- Ivana Borišev
- Department of Chemistry, Biochemistry and Environmental Protection, Faculty of Sciences, University of Novi Sad, Trg Dositeja Obradovića 3, Novi Sad, Serbia
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Piazzini V, Landucci E, Graverini G, Pellegrini-Giampietro DE, Bilia AR, Bergonzi MC. Stealth and Cationic Nanoliposomes as Drug Delivery Systems to Increase Andrographolide BBB Permeability. Pharmaceutics 2018; 10:pharmaceutics10030128. [PMID: 30104484 PMCID: PMC6161272 DOI: 10.3390/pharmaceutics10030128] [Citation(s) in RCA: 44] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2018] [Revised: 07/30/2018] [Accepted: 08/08/2018] [Indexed: 11/17/2022] Open
Abstract
(1) Background: Andrographolide (AG) is a natural compound effective for the treatment of inflammation-mediated neurodegenerative disorders. The aim of this investigation was the preparation of liposomes to enhance the penetration into the brain of AG, by modifying the surface of the liposomes by adding Tween 80 (LPs-AG) alone or in combination with Didecyldimethylammonium bromide (DDAB) (CLPs-AG). (2) Methods: LPs-AG and CLPs-AG were physically and chemically characterized. The ability of liposomes to increase the permeability of AG was evaluated by artificial membranes (PAMPA) and hCMEC/D3 cells. (3) Results: Based on obtained results in terms of size, homogeneity, ζ-potential and EE%. both liposomes are suitable for parenteral administration. The systems showed excellent stability during a month of storage as suspensions or freeze-dried products. Glucose resulted the best cryoprotectant agent. PAMPA and hCMEC/D3 transport studies revealed that LPs-AG and CLPs-AG increased the permeability of AG, about an order of magnitude, compared to free AG without alterations in cell viability. The caveolae-mediated endocytosis resulted the main mechanism of up-take for both formulations. The presence of positive charge increased the cellular internalization of nanoparticles. (4) Conclusions: This study shows that developed liposomes might be ideal candidates for brain delivery of AG.
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Affiliation(s)
- Vieri Piazzini
- Department of Chemistry, University of Florence, Via Ugo Schiff 6, Sesto Fiorentino, 50019 Florence, Italy.
| | - Elisa Landucci
- Department of Health Sciences, Section of Clinical Pharmacology and Oncology, University of Florence, Viale Pieraccini 6, 50139 Florence, Italy.
| | - Giulia Graverini
- Department of Chemistry, University of Florence, Via Ugo Schiff 6, Sesto Fiorentino, 50019 Florence, Italy.
| | - Domenico E Pellegrini-Giampietro
- Department of Health Sciences, Section of Clinical Pharmacology and Oncology, University of Florence, Viale Pieraccini 6, 50139 Florence, Italy.
| | - Anna Rita Bilia
- Department of Chemistry, University of Florence, Via Ugo Schiff 6, Sesto Fiorentino, 50019 Florence, Italy.
| | - Maria Camilla Bergonzi
- Department of Chemistry, University of Florence, Via Ugo Schiff 6, Sesto Fiorentino, 50019 Florence, Italy.
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Manatunga DC, de Silva RM, de Silva KMN, Malavige GN, Wijeratne DT, Williams GR, Jayasinghe CD, Udagama PV. Effective delivery of hydrophobic drugs to breast and liver cancer cells using a hybrid inorganic nanocarrier: A detailed investigation using cytotoxicity assays, fluorescence imaging and flow cytometry. Eur J Pharm Biopharm 2018; 128:18-26. [PMID: 29625162 DOI: 10.1016/j.ejpb.2018.04.001] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2017] [Revised: 03/30/2018] [Accepted: 04/02/2018] [Indexed: 02/07/2023]
Abstract
This study was focused on developing a drug carrier system composed of a polymer containing hydroxyapatite (HAp) shell and a magnetic core of iron oxide nanoparticles. Doxorubicin and/or curcumin were loaded into the carrier via a simple diffusion deposition approach, with encapsulation efficiencies (EE) for curcumin and doxorubicin of 93.03 ± 0.3% and 97.37 ± 0.12% respectively. The co-loading of curcumin and doxorubicin led to a total EE of 76.02 ± 0.48%. Release studies were carried out at pH 7.4 and 5.3, and revealed a greater extent of release at pH 5.3, showing the formulations to have potential applications in tumor microenvironments. Cytotoxicity assays, fluorescence imaging and flow cytometry demonstrated that the formulations could effectively inhibit the growth of MCF-7 (breast) and HEpG2 (liver) cancer cells, being more potent than the free drug molecules both in terms of dose and duration of action. Additionally, hemolysis tests and cytotoxicity evaluations determined the drug-loaded carriers to be non-toxic towards non-cancerous cells. These formulations thus have great potential in the development of new cancer therapeutics.
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Affiliation(s)
| | - Rohini M de Silva
- Department of Chemistry, University of Colombo, Colombo 00300, Sri Lanka.
| | - K M Nalin de Silva
- Department of Chemistry, University of Colombo, Colombo 00300, Sri Lanka; Sri Lanka Institute of Nanotechnology (SLINTEC), Nanotechnology & Science Park, Mahenwatte, Pitipana, Homagama 10206, Sri Lanka
| | - Gathsaurie Neelika Malavige
- Center for Dengue Research, Department of Microbiology, Faculty of Medical Sciences, University of Sri Jayewardenepura, 10250, Sri Lanka
| | - Dulharie T Wijeratne
- Center for Dengue Research, Department of Microbiology, Faculty of Medical Sciences, University of Sri Jayewardenepura, 10250, Sri Lanka
| | - Gareth R Williams
- UCL School of Pharmacy, University College London, 29-39 Brunswick Square, London WC1N 1AX, United Kingdom
| | | | - Preethi V Udagama
- Department of Zoology, University of Colombo, Colombo 00300, Sri Lanka
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Jhaveri A, Deshpande P, Pattni B, Torchilin V. Transferrin-targeted, resveratrol-loaded liposomes for the treatment of glioblastoma. J Control Release 2018. [PMID: 29522834 DOI: 10.1016/j.jconrel.2018.03.006] [Citation(s) in RCA: 196] [Impact Index Per Article: 28.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
Glioblastomas (GBMs) are highly aggressive brain tumors with a very grim prognosis even after multi-modal therapeutic regimens. Conventional chemotherapeutic agents frequently lead to drug resistance and result in severe toxicities to non-cancerous tissues. Resveratrol (RES), a natural polyphenol with pleiotropic health benefits, has proven chemopreventive effects in all the stages of cancer including initiation, promotion and progression. However, the poor physico-chemical properties of RES severely limit its use as a free drug. In this study, RES was loaded into PEGylated liposomes (RES-L) to counter its drawbacks as a free drug. Since transferrin receptors (TfRs) are up-regulated in GBM, the liposome surface was modified with transferrin moieties (Tf-RES-L) to make them cancer cell-specific. The liposomal nanomedicines developed in this project were aimed at enhancing the physico-chemical properties of RES and exploiting the passive and active targeting capabilities of liposomes to effectively treat GBM. The RES-L were stable, had a good drug-loading capacity, prolonged drug-release in vitro and were easily scalable. Flow cytometry and confocal microscopy were used to study the association with, and internalization of, Tf-L into U-87 MG cells. The Tf-RES-Ls were significantly more cytotoxic and induced higher levels of apoptosis accompanied by activation of caspases 3/7 in GBM cells when compared to free RES or RES-L. The ability of RES to arrest cells in the S-phase of the cell cycle, and selectively induce production of reactive oxygen species in cancer cells were probably responsible for its cytotoxic effects. The therapeutic efficacy of RES formulations was evaluated in a subcutaneous xenograft mouse model of GBM. A tumor growth inhibition study and a modified survival study showed that Tf-RES-Ls were more effective than other treatments in their ability to inhibit tumor growth and improve survival in mice. Overall, the liposomal nanomedicines of RES developed in this project exhibited favorable in vitro and in vivo efficacies, which warrant their further investigation for the treatment of GBMs.
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Affiliation(s)
- Aditi Jhaveri
- Center for Pharmaceutical Biotechnology and Nanomedicine, Department of Pharmaceutical Sciences, Northeastern University, Boston, MA 02115, USA
| | - Pranali Deshpande
- Center for Pharmaceutical Biotechnology and Nanomedicine, Department of Pharmaceutical Sciences, Northeastern University, Boston, MA 02115, USA
| | - Bhushan Pattni
- Center for Pharmaceutical Biotechnology and Nanomedicine, Department of Pharmaceutical Sciences, Northeastern University, Boston, MA 02115, USA
| | - Vladimir Torchilin
- Center for Pharmaceutical Biotechnology and Nanomedicine, Department of Pharmaceutical Sciences, Northeastern University, Boston, MA 02115, USA.
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Rizwanullah M, Amin S, Mir SR, Fakhri KU, Rizvi MMA. Phytochemical based nanomedicines against cancer: current status and future prospects. J Drug Target 2017; 26:731-752. [DOI: 10.1080/1061186x.2017.1408115] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Affiliation(s)
- Md. Rizwanullah
- Formulation Research Laboratory, Department of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi, India
| | - Saima Amin
- Formulation Research Laboratory, Department of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi, India
| | - Showkat Rasool Mir
- Phytopharmaceutical Laboratory, Department of Pharmacognosy and Phytochemistry, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi, India
| | - Khalid Umar Fakhri
- Genome Biology Lab, Department of Biosciences, Jamia Millia Islamia, New Delhi, India
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Nanomedicine, an emerging therapeutic strategy for oral cancer therapy. Oral Oncol 2017; 76:1-7. [PMID: 29290280 DOI: 10.1016/j.oraloncology.2017.11.014] [Citation(s) in RCA: 63] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2017] [Revised: 11/06/2017] [Accepted: 11/12/2017] [Indexed: 01/12/2023]
Abstract
Oral cavity and oropharyngeal carcinomas (oral cancer) represents a significant cause of morbidity and mortality. Despite efforts in improving early diagnosis and treatment, the 5-year survival rate of advanced stage of the disease is less than 63%. The field of nanomedicine has offered promising diagnostic and therapeutic advances in cancer. Indeed, several platforms have been clinically approved for cancer therapy, while other promising systems are undergoing exploration in clinical trials. With its ability to deliver drugs, nucleic acids, and MRI contrast agents with high efficiency, nanomedicine platforms offer the potential to improve drug efficacy and tolerability. The aim of the present mini-review is to summarize the current preclinical status of nanotechnology systems for oral cancer therapy. The nanoplatforms for delivery of chemopreventive agents presented herein resulted in significantly higher anti-tumor activity than free forms of the drug, even against a chemo-resistant cell line. Impressive results have also been obtained using nanoparticles to deliver chemotherapeutics, resulting in reduced toxicity both in vitro and in vivo. Nanoparticles have also led to improvements in efficacy of photodynamic therapies through the development of targeted magnetic nanoparticles. Finally, gene therapy using nanoparticles demonstrated promising results specifically with regards to inhibition of gene expression. Of the few in vivo studies that have been reported, many of these used animal models with several limitations, which will be discussed herein. Lastly, we will discuss several future perspectives in oral cancer nanoparticle-based therapy and the development of appropriate animal models, distinguishing between oral cavity and oropharyngeal carcinoma.
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Jiao Z, Li Y, Pang H, Zheng Y, Zhao Y. Pep-1 peptide-functionalized liposome to enhance the anticancer efficacy of cilengitide in glioma treatment. Colloids Surf B Biointerfaces 2017; 158:68-75. [DOI: 10.1016/j.colsurfb.2017.03.058] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2016] [Revised: 03/23/2017] [Accepted: 03/31/2017] [Indexed: 10/19/2022]
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Poonia M, Ramalingam K, Goyal S, Sidhu SK. Nanotechnology in oral cancer: A comprehensive review. J Oral Maxillofac Pathol 2017; 21:407-414. [PMID: 29391716 PMCID: PMC5763864 DOI: 10.4103/jomfp.jomfp_29_17] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2017] [Accepted: 11/03/2017] [Indexed: 11/24/2022] Open
Abstract
Oral health could be maintained by application of this technology in prevention, diagnosis and treatment. Oral cancer is a debilitating disease, and numerous research activities are being pursued worldwide to combat this deleterious process. Nanotechnology is very diverse field that has revolutionized the industry and is setting new trends in the management of oral cancer. Hence, we performed a PubMed search on nanotechnology in oral cancer and found 211 articles related to this search. We have reviewed the reported literature to the best of our abilities and summarized the various aspects of nanotechnology, its role in diagnosis - nanodiagnostics and treatment of oral cancer - nanotherapeutics in this article.
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Affiliation(s)
- Monika Poonia
- Department of Oral Pathology and Microbiology, Surendera Dental College and Research Institute, Rajasthan University of Health Sciences, Jaipur, Rajasthan, India
| | - Karthikeyan Ramalingam
- Department of Oral Pathology and Microbiology, Surendera Dental College and Research Institute, Rajasthan University of Health Sciences, Jaipur, Rajasthan, India
| | - Sandeep Goyal
- Department of Oral Pathology and Microbiology, Surendera Dental College and Research Institute, Rajasthan University of Health Sciences, Jaipur, Rajasthan, India
| | - Supreet Kaur Sidhu
- Department of Oral Pathology and Microbiology, Surendera Dental College and Research Institute, Rajasthan University of Health Sciences, Jaipur, Rajasthan, India
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Perrone D, Fuggetta MP, Ardito F, Cottarelli A, De Filippis A, Ravagnan G, De Maria S, Lo Muzio L. Resveratrol (3,5,4'-trihydroxystilbene) and its properties in oral diseases. Exp Ther Med 2017; 14:3-9. [PMID: 28672886 DOI: 10.3892/etm.2017.4472] [Citation(s) in RCA: 46] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2016] [Accepted: 12/19/2016] [Indexed: 02/07/2023] Open
Abstract
Health promotion strategies and lifestyle changes are important in disease prevention. Oral health has received a large amount of attention previously as it is a fundamental component of general health and it contributes to the quality of life. Therefore, the study of associations between diet, health and the presence of bioactive compounds in food is receiving a substantial amount of attention. In the present review the effects and targets of a natural polyohenolic stilbenoid compound; resveratrol (3,5,4'-trihydroxystilbene; RSV) is assessed, and the future prospects for RSV in promoting oral health are considered. RSV is a phytoalexin, synthesized by a wide range of plants and abundantly extracted in grape skin, it has been purported to exert a multiplicity of anti-inflammatory, anti-viral, anti-microbial, estrogenic, anticancer, cardioprotective, neuroprotective and immunomodulatory functions. In this review, following an introduction documenting the biochemistry of RSV and RSV glucosides, the bioavailability and pharmacokinetics of RSV are described. Considering its multiple properties, the present review has focused on the potential benefits of RSV as an antioxidant and chemopreventive agent.
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Affiliation(s)
- Donatella Perrone
- Department of Clinical and Experimental Medicine, University of Foggia, I-71122 Foggia, Italy
| | - Maria Pia Fuggetta
- Institute of Translational Pharmacology, CNR-Area Torvergata, I-00133 Rome, Italy
| | - Fatima Ardito
- Department of Clinical and Experimental Medicine, University of Foggia, I-71122 Foggia, Italy
| | - Andrea Cottarelli
- Institute of Translational Pharmacology, CNR-Area Torvergata, I-00133 Rome, Italy
| | - Anna De Filippis
- Department of Experimental Medicine, Second University of Napoli, Napoli, I-80131 Naples, Italy
| | - Giampietro Ravagnan
- Glures srl. Operative Unit-Biochemical and Biophysical Department, I-80138 Naples, Italy
| | - Salvatore De Maria
- Glures srl. Operative Unit-Biochemical and Biophysical Department, I-80138 Naples, Italy
| | - Lorenzo Lo Muzio
- Department of Clinical and Experimental Medicine, University of Foggia, I-71122 Foggia, Italy
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Doxorubicin and resveratrol co-delivery nanoparticle to overcome doxorubicin resistance. Sci Rep 2016; 6:35267. [PMID: 27731405 PMCID: PMC5059704 DOI: 10.1038/srep35267] [Citation(s) in RCA: 66] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2016] [Accepted: 09/27/2016] [Indexed: 02/08/2023] Open
Abstract
With the extensive application of doxorubicin (DOX), DOX resistance has become one of the main obstacles to the effective treatment of breast cancer. In this paper, DOX and resveratrol (RES) were co-encapsulated in a modified PLGA nanoparticle (NPS) to overcome the DOX resistance. CLSM results indicated that DOX and RES were simultaneously delivered into the nucleus of DOX-resistant human breast cancer cells by DOX/RES-loaded NPS. Consequently, DOX/RES-loaded NPS showed significant cytotoxicity on MDA-MB-231/ADR cells and MCF-7/ADR cells. Furthermore, DOX/RES-loaded NPS could overcome DOX resistance by inhibiting the expression of drug resistance-related protein such as P-gp, MRP-1 and BCRP, and induce apoptosis through down-regulating the expression of NF-κB and BCL-2. In tumor-bearing mice, DOX/RES-loaded NPS mainly delivered DOX and RES to tumor tissue. Compared with free DOX, DOX/RES-loaded NPS significantly inhibited the DOX-resistant tumor growth in tumor-bearing mice without causing significant systemic toxicity. In a word, DOX/RES-loaded NPS could overcome the DOX resistance and had the potential in the treatment of DOX-resistant breast cancer.
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Puglia C, Lauro MR, Tirendi GG, Fassari GE, Carbone C, Bonina F, Puglisi G. Modern drug delivery strategies applied to natural active compounds. Expert Opin Drug Deliv 2016; 14:755-768. [DOI: 10.1080/17425247.2017.1234452] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Affiliation(s)
- Carmelo Puglia
- Department of Drug Sciences, University of Catania, Catania, Italy
| | | | - Giorgia Giusy Tirendi
- Azienda Ospedaliera di Rilievo Nazionale e di Alta Specializzazione (ARNAS) Garibaldi, Catania, Italy
| | | | - Claudia Carbone
- Department of Drug Sciences, University of Catania, Catania, Italy
| | - Francesco Bonina
- Department of Drug Sciences, University of Catania, Catania, Italy
| | - Giovanni Puglisi
- Department of Drug Sciences, University of Catania, Catania, Italy
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48
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Nanocarriers based delivery of nutraceuticals for cancer prevention and treatment: A review of recent research developments. Trends Food Sci Technol 2016. [DOI: 10.1016/j.tifs.2016.06.003] [Citation(s) in RCA: 58] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
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Dalgic AD, Tezcaner A, Elci P, Sarper M, Arpaci F, Avcu F, Keskin D. Improvement of a liposomal formulation with a native molecule: calcitriol. RSC Adv 2016. [DOI: 10.1039/c6ra19187h] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
Calcitriol and doxorubicin co-loaded liposomes created improved cytotoxicity on Namalwa cells compared to doxorubicin loaded liposomes or free drug treatments.
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Affiliation(s)
- Ali Deniz Dalgic
- Department of Engineering Sciences
- Middle East Technical University
- Ankara
- 06800 Turkey
| | - Aysen Tezcaner
- Department of Engineering Sciences
- Middle East Technical University
- Ankara
- 06800 Turkey
- BIOMATEN
| | - Pinar Elci
- Cancer and Stem Cell Research Center
- Gulhane Military Medical Academy
- Ankara
- 06010 Turkey
| | - Meral Sarper
- Cancer and Stem Cell Research Center
- Gulhane Military Medical Academy
- Ankara
- 06010 Turkey
| | - Fikret Arpaci
- Department of Medical Oncology
- Gulhane Military Medical Academy
- Ankara
- 06010 Turkey
| | - Ferit Avcu
- Cancer and Stem Cell Research Center
- Gulhane Military Medical Academy
- Ankara
- 06010 Turkey
- Department of Medical Oncology
| | - Dilek Keskin
- Department of Engineering Sciences
- Middle East Technical University
- Ankara
- 06800 Turkey
- BIOMATEN
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