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Bhairu Khot K, Jose J, Gopan G, Sandeep DS, Ashtekar H, Shastry P, Raviraj C. Stearyl amine coated liposome of rotigotine alleviates cognitive deficit in Parkinson's disease induced mice model: modulation of oxidative stress, and motor coordination. Drug Dev Ind Pharm 2025; 51:606-621. [PMID: 40238494 DOI: 10.1080/03639045.2025.2494127] [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] [Revised: 03/28/2025] [Accepted: 04/11/2025] [Indexed: 04/18/2025]
Abstract
OBJECTIVE The study was conducted to evaluate the brain targeted delivery of cationic liposomes of rotigotine via nasal route, addressing the limitations in brain penetration for Parkinson's disease intervention. METHODS Cationic liposomes were fabricated and optimized using a Box-Behnken design to improve the excipient composition for effective intranasal delivery. The optimized liposome, LR12, was surface modified with stearylamine at three concentrations to confer a cationic charge. The final formulation, RTG-LP3, was evaluated for physicochemical parameters, including size, entrapment efficiency, and zeta potential. A morphological study was performed within the 100-200 nm size range. The cytotoxicity of RTG-LP3 was determined in SH-SY5Y cell lines, whereas pharmacodynamic studies were evaluated in C57BL/6 mice following nasal administration. RESULTS The formulation RTG-LP3 exhibited a minimal vesicle size of 162 ± 2.94 nm, a high entrapment efficiency of 86.53 ± 0.33%, and a positive zeta potential of +19.8 ± 2.45 mV. Morphological investigation indicated spherical shape of liposomes in the size range of 100-200 nm. Cytotoxicity study showed fivefold safety margin for RTG-LP3 when compared with rotigotine. Pharmacodynamic assessments in PD-induced C57BL6 mice showed increased motor coordination and antioxidant benefits following nasal treatment. Histological study of brain regions treated with RTG-LP3 demonstrated improved neuronal architecture, indicating reduced neurodegeneration and improved disease condition. CONCLUSION The cationic liposome RTG-LP3 demonstrated effective delivery of liposomes with superior therapeutic effects in treating PD via nasal route. These findings highlight the potential of cationic liposomes as a viable method for improving brain penetration and neuroprotection in PD therapy.
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Affiliation(s)
- Kartik Bhairu Khot
- Department of Pharmaceutics, NITTE (Deemed to be University), NGSM Institute of Pharmaceutical Sciences, Mangalore, India
| | - Jobin Jose
- Department of Pharmaceutics, NITTE (Deemed to be University), NGSM Institute of Pharmaceutical Sciences, Mangalore, India
| | - Gopika Gopan
- Department of Pharmaceutics, NITTE (Deemed to be University), NGSM Institute of Pharmaceutical Sciences, Mangalore, India
| | - D S Sandeep
- Department of Pharmaceutics, NITTE (Deemed to be University), NGSM Institute of Pharmaceutical Sciences, Mangalore, India
| | - Harsha Ashtekar
- Department of Pharmacology, NITTE (Deemed to be University), NGSM Institute of Pharmaceutical Sciences, Mangalore, India
| | - Prajna Shastry
- Department of Pharmaceutics, NITTE (Deemed to be University), NGSM Institute of Pharmaceutical Sciences, Mangalore, India
| | - Chaithra Raviraj
- Department of Advance Research Centre, NITTE (Deemed to be University), NGSM Institute of Pharmaceutical Sciences, Mangalore, India
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Yun Y, An J, Kim HJ, Choi HK, Cho HY. Recent advances in functional lipid-based nanomedicines as drug carriers for organ-specific delivery. NANOSCALE 2025; 17:7617-7638. [PMID: 40026004 DOI: 10.1039/d4nr04778h] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 03/04/2025]
Abstract
Lipid-based nanoparticles have emerged as promising drug delivery systems for a wide range of therapeutic agents, including plasmids, mRNA, and proteins. However, these nanoparticles still encounter various challenges in drug delivery, including drug leakage, poor solubility, and inadequate target specificity. In this comprehensive review, we present an in-depth investigation of four distinct drug delivery methods: liposomes, lipid nanoparticle formulations, solid lipid nanoparticles, and nanoemulsions. Moreover, we explore recent advances in lipid-based nanomedicines (LBNs) for organ-specific delivery, employing ligand-functionalized particles that specifically target receptors in desired organs. Through this strategy, LBNs enable direct and efficient drug delivery to the intended organs, leading to superior DNA or mRNA expression outcomes compared to conventional approaches. Importantly, the development of novel ligands and their judicious combination holds promise for minimizing the side effects associated with nonspecific drug delivery. By leveraging the unique properties of lipid-based nanoparticles and optimizing their design, researchers can overcome the limitations associated with current drug delivery systems. In this review, we aim to provide valuable insights into the advancements, challenges, and future directions of lipid-based nanoparticles in the field of drug delivery, paving the way for enhanced therapeutic strategies with improved efficacy and reduced adverse effects.
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Affiliation(s)
- Yeochan Yun
- Department of Bio & Fermentation Convergence Technology, Kookmin University, Seoul 02707, Republic of Korea.
| | - Jeongmin An
- Department of Bio & Fermentation Convergence Technology, Kookmin University, Seoul 02707, Republic of Korea.
| | - Hyun Joong Kim
- Department of Bio & Fermentation Convergence Technology, Kookmin University, Seoul 02707, Republic of Korea.
| | - Hye Kyu Choi
- Department of Chemistry and Chemical Biology, Rutgers University, the State University of New Jersey, 123 Bevier Road, Piscataway, New Jersey 08854, USA
| | - Hyeon-Yeol Cho
- Department of Bio & Fermentation Convergence Technology, Kookmin University, Seoul 02707, Republic of Korea.
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3
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Lagoa R, Rajan L, Violante C, Babiaka SB, Marques-da-Silva D, Kapoor B, Reis F, Atanasov AG. Application of curcuminoids in inflammatory, neurodegenerative and aging conditions - Pharmacological potential and bioengineering approaches to improve efficiency. Biotechnol Adv 2025; 82:108568. [PMID: 40157560 DOI: 10.1016/j.biotechadv.2025.108568] [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: 12/11/2024] [Revised: 03/21/2025] [Accepted: 03/22/2025] [Indexed: 04/01/2025]
Abstract
Curcumin, a natural compound found in turmeric, has shown promise in treating brain-related diseases and conditions associated with aging. Curcumin has shown multiple anti-inflammatory and brain-protective effects, but its clinical use is limited by challenges like poor absorption, specificity and delivery to the right tissues. A range of contemporary approaches at the intersection with bioengineering and systems biology are being explored to address these challenges. Data from preclinical and human studies highlight various neuroprotective actions of curcumin, including the inhibition of neuroinflammation, modulation of critical cellular signaling pathways, promotion of neurogenesis, and regulation of dopamine levels. However, curcumin's multifaceted effects - such as its impact on microRNAs and senescence markers - suggest novel therapeutic targets in neurodegeneration. Tetrahydrocurcumin, a primary metabolite of curcumin, also shows potential due to its presence in circulation and its anti-inflammatory properties, although further research is needed to elucidate its neuroprotective mechanisms. Recent advancements in delivery systems, particularly brain-targeting nanocarriers like polymersomes, micelles, and liposomes, have shown promise in enhancing curcumin's bioavailability and therapeutic efficacy in animal models. Furthermore, the exploration of drug-laden scaffolds and dermal delivery may extend the pharmacological applications of curcumin. Studies reviewed here indicate that engineered dermal formulations and devices could serve as viable alternatives for neuroprotective treatments and to manage skin or musculoskeletal inflammation. This work highlights the need for carefully designed, long-term studies to better understand how curcumin and its bioactive metabolites work, their safety, and their effectiveness.
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Affiliation(s)
- Ricardo Lagoa
- School of Technology and Management, Polytechnic Institute of Leiria, Morro do Lena-Alto do Vieiro, 2411-901 Leiria, Portugal; Laboratory of Separation and Reaction Engineering-Laboratory of Catalysis and Materials LSRE-LCM, Associate Laboratory in Chemical Engineering ALiCE, University of Porto, Rua Dr. Roberto Frias, 4200-465 Porto, Portugal; Applied Molecular Biosciences Unit UCIBIO, Institute for Health and Bioeconomy i4HB, NOVA University of Lisbon, 2829-516 Caparica, Portugal.
| | - Logesh Rajan
- Department of Pharmacognosy, SRM College of Pharmacy, SRM Institute of Science and Technology, Kattankulathur 603203, Tamil Nadu, India.
| | - Cristiana Violante
- School of Technology and Management, Polytechnic Institute of Leiria, Morro do Lena-Alto do Vieiro, 2411-901 Leiria, Portugal
| | - Smith B Babiaka
- Department of Chemistry, Faculty of Science, University of Buea, P.O. Box 63, Buea, Cameroon; Department of Microbial Bioactive Compounds, Interfaculty Institute for Microbiology and Infection Medicine, University of Tübingen, 72076 Tübingen, Germany.
| | - Dorinda Marques-da-Silva
- School of Technology and Management, Polytechnic Institute of Leiria, Morro do Lena-Alto do Vieiro, 2411-901 Leiria, Portugal; Laboratory of Separation and Reaction Engineering-Laboratory of Catalysis and Materials LSRE-LCM, Associate Laboratory in Chemical Engineering ALiCE, University of Porto, Rua Dr. Roberto Frias, 4200-465 Porto, Portugal.
| | - Bhupinder Kapoor
- School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab 144411, India
| | - Flávio Reis
- Institute of Pharmacology and Experimental Therapeutics & Coimbra Institute for Clinical and Biomedical Research iCBR, Faculty of Medicine, University of Coimbra, 3004-504 Coimbra, Portugal; Center for Innovative Biomedicine and Biotechnology CIBB, University of Coimbra, 3000-548 Coimbra, Portugal; Clinical Academic Center of Coimbra, 3004-531 Coimbra, Portugal.
| | - Atanas G Atanasov
- Institute of Genetics and Animal Biotechnology of the Polish Academy of Sciences, 05-552 Magdalenka, Poland; Laboratory of Natural Products and Medicinal Chemistry LNPMC, Center for Global Health Research, Saveetha Medical College and Hospital, Saveetha Institute of Medical and Technical Sciences SIMATS, Thandalam, Chennai, India; Ludwig Boltzmann Institute Digital Health and Patient Safety, Medical University of Vienna, Spitalgasse 23, 1090 Vienna, Austria.
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4
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Altaf Z, Ahmad Z, Mahmood A, Shchinar S, Latif R. Dissolving microneedle patch for transdermal delivery of perindopril erbumine. Inflammopharmacology 2025; 33:1381-1391. [PMID: 40009346 DOI: 10.1007/s10787-025-01696-z] [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: 01/15/2025] [Accepted: 01/31/2025] [Indexed: 02/27/2025]
Abstract
Perindopril Erbumine is a widely used angiotensin-converting enzyme (ACE) inhibitor for managing hypertension and cardiovascular diseases. Its dual action of lowering blood pressure and mitigating inflammation makes it a cornerstone treatment in these conditions. However, its oral administration often results in suboptimal bioavailability and gastrointestinal side effects. This study aimed to develop and characterize a dissolving microneedle (dMN) patch for the transdermal delivery of Perindopril Erbumine to enhance therapeutic efficacy and patient compliance. A Perindopril Erbumine-loaded microneedle patch was fabricated using chitosan and polyvinyl alcohol (PVA) using the solvent casting method. The microneedle patch was evaluated for physical properties, mechanical strength, drug loading, and moisture content. Ex-vivo permeation through rat skin and in-vivo pharmacokinetic studies in rabbits was conducted to compare its performance with a marketed oral Perindopril Erbumine formulation. The developed patch demonstrated effective skin penetration, controlled drug release, and a six-fold enhancement in cumulative drug permeation (82.45% ± 1.54) compared to the oral solution (14.32% ± 1.60). The pharmacokinetic study revealed prolonged drug release, with a 7.9-fold increase in half-life (7.739 ± 0.243 h vs. 0.986 ± 0.93 h) and a significantly higher area under the curve (AUC) for the microneedle patch. Skin irritation studies confirmed the biocompatibility of the formulation, with no significant adverse effects observed. These findings highlight the potential of Perindopril Erbumine-loaded dissolving microneedles as a promising transdermal delivery system for improved therapeutic outcomes in managing hypertension and inflammation-related vascular conditions, potentially reducing inflammation through enhanced and targeted drug delivery.
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Affiliation(s)
- Zunaira Altaf
- Riphah Institute of Pharmaceutical Sciences (RIPS), Riphah International University, Lahore Campus, Lahore, Pakistan
| | - Zulcaif Ahmad
- Riphah Institute of Pharmaceutical Sciences (RIPS), Riphah International University, Lahore Campus, Lahore, Pakistan.
| | - Asif Mahmood
- Department of Pharmacy, University of Chakwal, Chakwal, Pakistan
| | - Saniia Shchinar
- Department of Pharmaceutical Sciences, Avera Health and Science, South Dakota State University, Brookings, USA
| | - Riffat Latif
- Department of Pharmaceutical Sciences, Avera Health and Science, South Dakota State University, Brookings, USA
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5
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Bandiwadekar A, Jose J, Gopan G, Augustin V, Ashtekar H, Khot KB. Transdermal delivery of resveratrol loaded solid lipid nanoparticle as a microneedle patch: a novel approach for the treatment of Parkinson's disease. Drug Deliv Transl Res 2025; 15:1043-1073. [PMID: 38949746 DOI: 10.1007/s13346-024-01656-0] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/15/2024] [Indexed: 07/02/2024]
Abstract
Parkinson's disease (PD), affecting millions of people worldwide and expected to impact 10 million by 2030, manifests a spectrum of motor and non-motor symptoms linked to the decline of dopaminergic neurons. Current therapies manage PD symptoms but lack efficacy in slowing disease progression, emphasizing the urgency for more effective treatments. Resveratrol (RSV), recognized for its neuroprotective and antioxidative properties, encounters challenges in clinical use for PD due to limited bioavailability. Researchers have investigated lipid-based nanoformulations, specifically solid lipid nanoparticles (SLNs), to enhance RSV stability. Oral drug delivery via SLNs faces obstacles, prompting exploration into transdermal delivery using SLNs integrated with microneedles (MNs) for improved patient compliance. In this study, an RSV-loaded SLNs (RSV -SLNs) incorporated into the MN patch was developed for transdermal RSV delivery to improve its stability and patient compliance. Characterization studies demonstrated favorable physical properties of SLNs with a sustained drug release profile of 78.36 ± 0.74%. The developed MNs exhibited mechanical robustness and skin penetration capabilities. Ex vivo permeation studies displayed substantial drug permeation of 68.39 ± 1.4% through the skin. In an in vivo pharmacokinetic study, the RSV-SLNs delivered through MNs exhibited a significant increase in Cmax, Tmax, and AUC0 - t values, alongside a reduced elimination rate in blood plasma in contrast to the administration of pure RSV via MNs. Moreover, an in vivo study showcased enhanced behavioral functioning and increased brain antioxidant levels in the treated animals. In-vivo skin irritation study revealed no signs of irritation till 24 h which permits long-term MNs application. Histopathological analysis showed notable changes in the brain regions of the rat, specifically the striatum and substantia nigra, after the completion of the treatment. Based on these findings, the development of an RSV-SLN loaded MNs (RSVSNLMP) patch presents a novel approach, with the potential to enhance the drug's efficiency, patient compliance, and therapeutic outcomes for PD, offering a promising avenue for advanced PD therapy.
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Affiliation(s)
- Akshay Bandiwadekar
- NGSM Institute of Pharmaceutical Sciences, Department of Pharmaceutics,, NITTE Deemed-to-be University, Mangalore, 575018, India
| | - Jobin Jose
- NGSM Institute of Pharmaceutical Sciences, Department of Pharmaceutics,, NITTE Deemed-to-be University, Mangalore, 575018, India.
| | - Gopika Gopan
- NGSM Institute of Pharmaceutical Sciences, Department of Pharmaceutics,, NITTE Deemed-to-be University, Mangalore, 575018, India
| | - Varsha Augustin
- NGSM Institute of Pharmaceutical Sciences, NITTE Deemed-to-be University, Department of NITTE University Center for Animal Research & Experimentation (NUCARE), Mangalore, 575018, India
| | - Harsha Ashtekar
- NGSM Institute of Pharmaceutical Sciences, Department of Pharmacology, NITTE Deemed-to-be University, Mangalore, 575018, India
| | - Kartik Bhairu Khot
- NGSM Institute of Pharmaceutical Sciences, Department of Pharmaceutics,, NITTE Deemed-to-be University, Mangalore, 575018, India
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6
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Patil A, Rajput A, Subbappa P, Pawar A. Formulation, development and in vivo characterization of selegiline hydrochloride nanostructured lipid nanocarrier loaded microneedle array patch for depression. Int J Pharm 2025; 671:125257. [PMID: 39855281 DOI: 10.1016/j.ijpharm.2025.125257] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2024] [Revised: 12/15/2024] [Accepted: 01/20/2025] [Indexed: 01/27/2025]
Abstract
Depression is a common mental condition causing depressed mood and loss of pleasure. The primary treatment approach for the management of depression consists of the use of selegiline (MAO-B) inhibitor compound. The present work aimed to develop and optimize selegiline-loaded nanostructured lipid carriers for transdermal application, utilizing a 23 full factorial design approach. The optimized nanostructured lipid carriers formulation (Batch B7) demonstrated a particle size of 158.71 ± 0.56 nm, a narrow size distribution (0.266 ± 0.006), high entrapment efficiency (59.60 ± 0.34 %), and a zeta potential of -23.2 ± 2.21 mV. Furthermore, x-ray diffraction and differential scanning calorimetry studies revealed the amorphous transformation of selegiline within the nanostructured lipid carrier. Transmission Electron Microscopy study has shown that nanostructured lipid carrier particles had a spherical shape with a smooth surface. These optimized nanostructured lipid carriers were then incorporated into a microneedle array patch for transdermal delivery. The selegiline-loaded nanostructured lipid carrier microneedle array patch exhibited no skin irritation in a rabbit model. It enhanced drug diffusion ex vivo (1.13-fold compared to pure selegiline-loaded microneedle array patch) with 90 % drug release in 12 h. The pharmacokinetic study demonstrated a steady and controlled release profile with a half-life of 29.9 ± 0.14 h and AUC0-t (26.57 ± 0.51 μg/ml*h) of selegiline loaded nanostructured lipid carrier microneedle array patch. On the contrary, a pure selegiline-loaded microneedle array patch showed a short half-life of 6.5 ± 0.26 h and AUC0-t (20.90 ± 0.31 μg/ml*h). The sustained release profile and prolonged half-life in plasma and the brain suggest improved therapeutic efficacy. Histopathology analysis revealed no significant toxicity to vital organs. Thus, a selegiline nanostructured lipid carrier-loaded microneedle array patch can increase brain bioavailability compared to a pure selegiline-loaded microneedle array patch for managing depression.
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Affiliation(s)
- Anuradha Patil
- Department of Pharmaceutics, Bharti Vidyapeeth Deemed to be University, Poona College of Pharmacy, Erandwane, Pune 411038, Maharashtra, India
| | - Amarjitsing Rajput
- Department of Pharmaceutics, Bharti Vidyapeeth Deemed to be University, Poona College of Pharmacy, Erandwane, Pune 411038, Maharashtra, India
| | - Praveen Subbappa
- Alliance Management and Supply Chain, Azurity Pharmaceuticals, Inc., 8 Cabot Road, Suite 2000, Woburn, MA 01801, USA
| | - Atmaram Pawar
- Department of Pharmaceutics, Bharti Vidyapeeth Deemed to be University, Poona College of Pharmacy, Erandwane, Pune 411038, Maharashtra, India.
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7
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Hallan SS, Ferrara F, Cortesi R, Sguizzato M. Potential of the Nano-Encapsulation of Antioxidant Molecules in Wound Healing Applications: An Innovative Strategy to Enhance the Bio-Profile. Molecules 2025; 30:641. [PMID: 39942745 PMCID: PMC11820390 DOI: 10.3390/molecules30030641] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2024] [Revised: 01/21/2025] [Accepted: 01/25/2025] [Indexed: 02/16/2025] Open
Abstract
Naturally available antioxidants offer remarkable medicinal applications in wound healing. However, the encapsulation of these phytoactive moieties into suitable nano-scale drug delivery systems has always been challenging due to their inherent characteristics, such as low molecular weight, poor aqueous solubility, and inadequate skin permeability. Here, we provide a systematic review focusing on the major obstacles hindering the development of various lipid and polymer-based drug transporters to carry these cargos to the targeted site. Additionally, this review covers the possibility of combining the effects of a polymer and a lipid within one system, which could increase the skin permeability threshold. Moreover, the lack of suitable physical characterization techniques and the challenges associated with scaling up the progression of these nano-carriers limit their utility in biomedical applications. In this context, consistent progressive approaches for addressing these shortcomings are introduced, and their prospects are discussed in detail.
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Affiliation(s)
- Supandeep Singh Hallan
- Department of Pharmaceutical Sciences and Natural Products, Central University of Punjab, Bathinda 151401, India
| | - Francesca Ferrara
- Department of Chemical, Pharmaceutical and Agricultural Sciences, University of Ferrara, I-44121 Ferrara, Italy; (F.F.); (M.S.)
| | - Rita Cortesi
- Department of Chemical, Pharmaceutical and Agricultural Sciences, University of Ferrara, I-44121 Ferrara, Italy; (F.F.); (M.S.)
- Biotechnology Interuniversity Consortium (C.I.B.), Ferrara Section, University of Ferrara, I-44121 Ferrara, Italy
| | - Maddalena Sguizzato
- Department of Chemical, Pharmaceutical and Agricultural Sciences, University of Ferrara, I-44121 Ferrara, Italy; (F.F.); (M.S.)
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8
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Can Karaca A, Rezaei A, Qamar M, Assadpour E, Esatbeyoglu T, Jafari SM. Lipid-based nanodelivery systems of curcumin: Recent advances, approaches, and applications. Food Chem 2025; 463:141193. [PMID: 39276542 DOI: 10.1016/j.foodchem.2024.141193] [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: 03/28/2024] [Revised: 09/03/2024] [Accepted: 09/06/2024] [Indexed: 09/17/2024]
Abstract
Despite its many beneficial effects, pharmaceutical applications of curcumin (CUR) are limited due to its chemical instability, low solubility/absorption and weak bioavailability. Recent advances in nanotechnology have enabled the development of CUR-loaded nanodelivery systems to tackle those issues. Within many different nanocarriers developed for CUR up to date, lipid-based nanocarriers (LBNs) are among the most extensively studied systems. LBNs such as nanoemulsions, solid lipid carriers, nanostructured phospholipid/surfactant carriers are shown to be potential delivery systems capable of improving the solubility, bioavailability, and chemical stability of CUR. The particle characteristics, stability, bioavailability, and release properties of CUR-loaded LBNs can be tailored via optimizing the formulation and processing parameters. This paper reviews the most recent studies on the development of various CUR-loaded LBNs. Approaches to the improvement of CUR bioavailability and release characteristics of LBNs are discussed. Furthermore, challenges in the development of CUR-loaded LBNs and their potential applications are presented.
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Affiliation(s)
- Asli Can Karaca
- Department of Food Engineering, Faculty of Chemical and Metallurgical Engineering, Istanbul Technical University, 34469 Istanbul, Turkey.
| | - Atefe Rezaei
- Department of Food Science and Technology, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran; Nutrition and Food Security Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Muhammad Qamar
- Institute of Food Science and Nutrition, Bahauddin Zakariya University, Multan 60800, Pakistan
| | - Elham Assadpour
- Food Industry Research Co., Gorgan, Iran; Food and Bio-Nanotech International Research Center (Fabiano), Gorgan University of Agricultural Sciences and Natural Resources, Gorgan, Iran
| | - Tuba Esatbeyoglu
- Department of Molecular Food Chemistry and Food Development, Institute of Food and One Health, Gottfried Wilhelm Leibniz University Hannover, Am Kleinen Felde 30, 30167 Hannover, Germany
| | - Seid Mahdi Jafari
- Department of Food Materials and Process Design Engineering, Gorgan University of Agricultural Sciences and Natural Resources, Gorgan, Iran; Halal Research Center of IRI, Iran Food and Drug Administration, Ministry of Health and Medical Education, Tehran, Iran.
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Liu Y, Yin R, Tian Y, Xu S, Meng X. Curcumin nanopreparations: recent advance in preparation and application. Biomed Mater 2024; 19:052009. [PMID: 39189065 DOI: 10.1088/1748-605x/ad6dc7] [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: 04/15/2024] [Accepted: 08/09/2024] [Indexed: 08/28/2024]
Abstract
Curcumin is a natural polyphenolic compound extracted from turmeric with antibacterial, antioxidant, antitumor, preventive and therapeutic neurological disorders and a variety of bioactivities, which is widely used in the field of food and medicine. However, the drawbacks of curcumin such as poor aqueous solubility and stability have limited the practical application of curcumin. To overcome these defects and enhance its functional properties, various nanoscale systems (liposomes, polymer nanoparticles, protein nanoparticles, solid lipid nanoparticles, metal nanoparticles, etc) have been extensively employed for curcumin encapsulation and delivery. Despite the rapid development of curcumin nanoformulations, there is a lack of comprehensive reviews on their preparation and properties. This review provides an overview of the construction of curcumin nano-delivery systems, mechanisms of action, nanocarrier preparation methods and the applications of curcumin nanocarriers in the food and pharmaceutical fields to provide a theoretical basis and technological support for the efficient bio-utilization, product development and early clinical application of curcumin.
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Affiliation(s)
- Yan Liu
- School of Pharmacy, Heilongjiang University of Chinese Medicine, NO.24 Heping Road, Harbin, 150040, People's Republic of China
| | - Rui Yin
- School of Pharmacy, Heilongjiang University of Chinese Medicine, NO.24 Heping Road, Harbin, 150040, People's Republic of China
| | - Yuan Tian
- School of Pharmacy, Heilongjiang University of Chinese Medicine, NO.24 Heping Road, Harbin, 150040, People's Republic of China
| | - Shujun Xu
- School of Pharmacy, Heilongjiang University of Chinese Medicine, NO.24 Heping Road, Harbin, 150040, People's Republic of China
| | - Xin Meng
- School of Pharmacy, Heilongjiang University of Chinese Medicine, NO.24 Heping Road, Harbin, 150040, People's Republic of China
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10
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Yashmi F, Fakhri S, Shiri Varnamkhasti B, Amin MN, Khirehgesh MR, Mohammadi-Noori E, Hosseini M, Khan H. Defining the mechanisms behind the hepatoprotective properties of curcumin. Arch Toxicol 2024; 98:2331-2351. [PMID: 38837048 DOI: 10.1007/s00204-024-03758-7] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2024] [Accepted: 04/09/2024] [Indexed: 06/06/2024]
Abstract
As a critical cause of human dysfunctionality, hepatic failure leads to approximately two million deaths per year and is on the rise. Considering multiple inflammatory, oxidative, and apoptotic mechanisms behind hepatotoxicity, it urges the need for finding novel multi-targeting agents. Curcumin is a phenolic compound with anti-inflammatory, antioxidant, and anti-apoptotic roles. Curcumin possesses auspicious health benefits and protects against several diseases with exceptional safety and tolerability. This review focused on the hepatoprotective mechanisms of curcumin. The need to develop novel delivery systems of curcumin (e.g., nanoparticles, self-micro emulsifying, lipid-based colloids, solid lipid nanoparticles, cyclodextrin inclusion, phospholipid complexes, and nanoemulsions) is also considered.
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Affiliation(s)
- Farinam Yashmi
- Department of Pharmacy, Acibadem University, Istanbul, Turkey
| | - Sajad Fakhri
- Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran.
| | - Behrang Shiri Varnamkhasti
- Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Mohammed Namiq Amin
- Student Research Committee, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Mohammad Reza Khirehgesh
- Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Ehsan Mohammadi-Noori
- Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Mahsa Hosseini
- Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Haroon Khan
- Department of Pharmacy, Abdul Wali Khan University Mardan, Mardan, 23200, Pakistan.
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Saadh MJ, Shallan MA, Hussein UAR, Mohammed AQ, Al-Shuwaili SJ, Shikara M, Ami AA, Khalil NAMA, Ahmad I, Abbas HH, Elawady A. Advances in microscopy characterization techniques for lipid nanocarriers in drug delivery: a comprehensive review. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2024; 397:5463-5481. [PMID: 38459989 DOI: 10.1007/s00210-024-03033-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/16/2023] [Accepted: 02/28/2024] [Indexed: 03/11/2024]
Abstract
This review paper provides an in-depth analysis of the significance of lipid nanocarriers in drug delivery and the crucial role of characterization techniques. It explores various types of lipid nanocarriers and their applications, emphasizing the importance of microscopy-based characterization methods such as light microscopy, confocal microscopy, transmission electron microscopy (TEM), scanning electron microscopy (SEM), and atomic force microscopy (AFM). The paper also delves into sample preparation, quantitative analysis, challenges, and future directions in the field. The review concludes by underlining the pivotal role of microscopy-based characterization in advancing lipid nanocarrier research and drug delivery technologies.
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Affiliation(s)
- Mohamed J Saadh
- Faculty of Pharmacy, Middle East University, Amman, 11831, Jordan
| | | | | | | | | | | | - Ahmed Ali Ami
- Department of Medical Laboratories Technology, Al-Nisour University College, Baghdad, Iraq
| | | | - Irfan Ahmad
- Department of Clinical Laboratory Sciences, College of Applied Medical Science, King Khalid University, Abha, Saudi Arabia
| | - Huda Hayder Abbas
- College of Pharmacy, National University of Science and Technology, Dhi Qar, Iraq
| | - Ahmed Elawady
- College of Technical Engineering, The Islamic University, Najaf, Iraq.
- College of Technical Engineering, The Islamic University of Al Diwaniyah, Al Diwaniyah, Iraq.
- College of Technical Engineering, The Islamic University of Babylon, Babylon, Iraq.
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12
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Babu MR, Vishwas S, Khursheed R, Harish V, Sravani AB, Khan F, Alotaibi B, Binshaya A, Disouza J, Kumbhar PS, Patravale V, Gupta G, Loebenberg R, Arshad MF, Patel A, Patel S, Dua K, Singh SK. Unravelling the role of microneedles in drug delivery: Principle, perspectives, and practices. Drug Deliv Transl Res 2024; 14:1393-1431. [PMID: 38036849 DOI: 10.1007/s13346-023-01475-9] [Citation(s) in RCA: 12] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/04/2023] [Indexed: 12/02/2023]
Abstract
In recent year, the research of transdermal drug delivery systems has got substantial attention towards the development of microneedles (MNs). This shift has occurred due to multifaceted advantages of MNs as they can be utilized to deliver the drug deeper to the skin with minimal invasion, offer successful delivery of drugs and biomolecules that are susceptible to degradation in gastrointestinal tract (GIT), act as biosensors, and help in monitoring the level of biomarkers in the body. These can be fabricated into different types based on their applications as well as material for fabrication. Some of their types include solid MNs, hollow MNs, coated MNs, hydrogel forming MNs, and dissolving MNs. These MNs deliver the therapeutics via microchannels deeper into the skin. The coated and hollow MNs have been found successful. However, they suffer from poor drug loading and blocking of pores. In contrast, dissolving MNs offer high drug loading. These MNs have also been utilized to deliver vaccines and biologicals. They have also been used in cosmetics. The current review covers the different types of MNs, materials used in their fabrication, properties of MNs, and various case studies related to their role in delivering therapeutics, monitoring level of biomarkers/hormones in body such as insulin. Various patents and clinical trials related to MNs are also covered. Covered are the major bottlenecks associated with their clinical translation and potential future perspectives.
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Affiliation(s)
- Molakpogu Ravindra Babu
- School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, 144411, Punjab, India
| | - Sukriti Vishwas
- School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, 144411, Punjab, India
| | - Rubiya Khursheed
- School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, 144411, Punjab, India
| | - Vancha Harish
- School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, 144411, Punjab, India
| | - Anne Boyina Sravani
- Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, India
| | - Farhan Khan
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Al- Quwayiyah, Shaqra University, Riyadh, Saudi Arabia
| | - Bader Alotaibi
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Al- Quwayiyah, Shaqra University, Riyadh, Saudi Arabia
| | - Abdulkarim Binshaya
- Department of Medical Laboratory Sciences, College of Applied Medical Sciences, Prince Sattam Bin Abdulaziz University, Al Kharj, Saudi Arabia
| | - John Disouza
- Tatyasaheb Kore College of Pharmacy, Warananagar, Tal: Panhala , Kolhapur, Maharashtra, 416113, India
| | - Popat S Kumbhar
- Tatyasaheb Kore College of Pharmacy, Warananagar, Tal: Panhala , Kolhapur, Maharashtra, 416113, India
| | - Vandana Patravale
- Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, Matunga, Mumbai, Maharashtra, 400019, India
| | - Gaurav Gupta
- Centre for Global Health Research, Saveetha Medical College, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, India
- School of Pharmacy, Graphic Era Hill University, Dehradun, 248007, India
- School of Pharmacy, Suresh Gyan Vihar University, Mahal Road, Jagatpura , 30201, Jaipur, India
| | - Raimar Loebenberg
- University of Alberta, Faculty of Pharmacy and Pharmaceutical Sciences, Edmonton , AB T6G2N8, Alberta, Canada
| | - Mohammed Faiz Arshad
- Department of Scientific Communications, Isthmus Research and Publishing House, New Delhi, 110044, India
| | - Archita Patel
- Ramanbhai Patel College of Pharmacy, Charotar University of Science and Technology, CHARUSAT Campus, At & Post: Changa, Tal.:- Petlad, Dist.:- Anand-388 421, Gujarat, India
| | - Samir Patel
- Ramanbhai Patel College of Pharmacy, Charotar University of Science and Technology, CHARUSAT Campus, At & Post: Changa, Tal.:- Petlad, Dist.:- Anand-388 421, Gujarat, India
| | - Kamal Dua
- Discipline of Pharmacy, Graduate School of Health, University of Technology Sydney, Ultimo, NSW, 2007, Australia
- Faculty of Health, Australian Research Centre in Complementary and Integrative Medicine, University of Technology Sydney, Ultimo, NSW 2007, Australia
- Uttaranchal Institute of Pharmaceutical Sciences, Uttaranchal University, Dehradun, India
| | - Sachin Kumar Singh
- School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, 144411, Punjab, India.
- Faculty of Health, Australian Research Centre in Complementary and Integrative Medicine, University of Technology Sydney, Ultimo, NSW 2007, Australia.
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13
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Arabestani MR, Bigham A, Kamarehei F, Dini M, Gorjikhah F, Shariati A, Hosseini SM. Solid lipid nanoparticles and their application in the treatment of bacterial infectious diseases. Biomed Pharmacother 2024; 174:116433. [PMID: 38508079 DOI: 10.1016/j.biopha.2024.116433] [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: 12/20/2023] [Revised: 03/02/2024] [Accepted: 03/15/2024] [Indexed: 03/22/2024] Open
Abstract
Nano pharmacology is considered an effective, safe, and applicable approach for drug delivery applications. Solid lipid nanoparticle (SLNs) colloids contain biocompatible lipids which are capable of encapsulating and maintaining hydrophilic or hydrophobic drugs in the solid matrix followed by releasing the drug in a sustained manner in the target site. SLNs have more promising potential than other drug delivery systems for various purposes. Nowadays, the SLNs are used as a carrier for antibiotics, chemotherapeutic drugs, nucleic acids, herbal compounds, etc. The SLNs have been widely applied in biomedicine because of their non-toxicity, biocompatibility, and simple production procedures. In this review, the complications related to the optimization, preparation process, routes of transplantation, uptake and delivery system, and release of the loaded drug along with the advantages of SLNs as therapeutic agents were discussed.
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Affiliation(s)
- Mohammad Reza Arabestani
- Nutrition Health Research Center, Hamadan University of Medical Sciences, Hamadan, Iran; Department of Microbiology, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Ashkan Bigham
- Institute of Polymers, Composites, and Biomaterials, National Research Council (IPCB-CNR), Naples 80125, Italy; Department of Chemical, Materials and Production Engineering, University of Naples Federico II, Piazzale V. Tecchio 80, Naples 80125, Italy
| | - Farideh Kamarehei
- Department of Microbiology, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Mahya Dini
- Department of Microbiology, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Fatemeh Gorjikhah
- University reference laboratory, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Aref Shariati
- Infectious Diseases Research Center (IDRC), Arak University of medical sciences, Arak, Iran
| | - Seyed Mostafa Hosseini
- Department of Microbiology, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran; Infectious Disease Research Center, Hamadan University of Medical Sciences, Hamadan, Iran.
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14
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Zhang H, Pan Y, Hou Y, Li M, Deng J, Wang B, Hao S. Smart Physical-Based Transdermal Drug Delivery System:Towards Intelligence and Controlled Release. SMALL (WEINHEIM AN DER BERGSTRASSE, GERMANY) 2024; 20:e2306944. [PMID: 37852939 DOI: 10.1002/smll.202306944] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/13/2023] [Revised: 10/05/2023] [Indexed: 10/20/2023]
Abstract
Transdermal drug delivery systems based on physical principles have provided a stable, efficient, and safe strategy for disease therapy. However, the intelligent device with real-time control and precise drug release is required to enhance treatment efficacy and improve patient compliance. This review summarizes the recent developments, application scenarios, and drug release characteristics of smart transdermal drug delivery systems fabricated with physical principle. Special attention is paid to the progress of intelligent design and concepts in of physical-based transdermal drug delivery technologies for real-time monitoring and precise drug release. In addition, facing with the needs of clinical treatment and personalized medicine, the recent progress and trend of physical enhancement are further highlighted for transdermal drug delivery systems in combination with pharmaceutical dosage forms to achieve better transdermal effects and facilitate the development of smart medical devices. Finally, the next generation and future application scenarios of smart physical-based transdermal drug delivery systems are discussed, a particular focus in vaccine delivery and tumor treatment.
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Affiliation(s)
- Haojie Zhang
- Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing, 400044, China
| | - Yinping Pan
- Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing, 400044, China
| | - Yao Hou
- Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing, 400044, China
| | - Minghui Li
- Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing, 400044, China
| | - Jia Deng
- College of Environment and Resources, Chongqing Technology and Business University, Chongqing, 400067, China
| | - Bochu Wang
- Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing, 400044, China
| | - Shilei Hao
- Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing, 400044, China
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15
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Chang Z, Wu Y, Hu P, Jiang J, Quan G, Wu C, Pan X, Huang Z. The Necessity to Investigate In Vivo Fate of Nanoparticle-Loaded Dissolving Microneedles. Pharmaceutics 2024; 16:286. [PMID: 38399340 PMCID: PMC10892231 DOI: 10.3390/pharmaceutics16020286] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2023] [Revised: 02/09/2024] [Accepted: 02/15/2024] [Indexed: 02/25/2024] Open
Abstract
Transdermal drug delivery systems are rapidly gaining prominence and have found widespread application in the treatment of numerous diseases. However, they encounter the challenge of a low transdermal absorption rate. Microneedles can overcome the stratum corneum barrier to enhance the transdermal absorption rate. Among various types of microneedles, nanoparticle-loaded dissolving microneedles (DMNs) present a unique combination of advantages, leveraging the strengths of DMNs (high payload, good mechanical properties, and easy fabrication) and nanocarriers (satisfactory solubilization capacity and a controlled release profile). Consequently, they hold considerable clinical application potential in the precision medicine era. Despite this promise, no nanoparticle-loaded DMN products have been approved thus far. The lack of understanding regarding their in vivo fate represents a critical bottleneck impeding the clinical translation of relevant products. This review aims to elucidate the current research status of the in vivo fate of nanoparticle-loaded DMNs and elaborate the necessity to investigate the in vivo fate of nanoparticle-loaded DMNs from diverse aspects. Furthermore, it offers insights into potential entry points for research into the in vivo fate of nanoparticle-loaded DMNs, aiming to foster further advancements in this field.
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Affiliation(s)
- Ziyao Chang
- School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510006, China; (Z.C.); (Y.W.); (X.P.)
| | - Yuhuan Wu
- School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510006, China; (Z.C.); (Y.W.); (X.P.)
| | - Ping Hu
- College of Pharmacy, Jinan University, Guangzhou 511443, China; (P.H.); (G.Q.); (C.W.)
| | - Junhuang Jiang
- College of Pharmacy, Jinan University, Guangzhou 511443, China; (P.H.); (G.Q.); (C.W.)
| | - Guilan Quan
- College of Pharmacy, Jinan University, Guangzhou 511443, China; (P.H.); (G.Q.); (C.W.)
| | - Chuanbin Wu
- College of Pharmacy, Jinan University, Guangzhou 511443, China; (P.H.); (G.Q.); (C.W.)
| | - Xin Pan
- School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510006, China; (Z.C.); (Y.W.); (X.P.)
| | - Zhengwei Huang
- College of Pharmacy, Jinan University, Guangzhou 511443, China; (P.H.); (G.Q.); (C.W.)
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16
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Bandiwadekar A, Khot KB, Gopan G, Jose J. Microneedles: A Versatile Drug Delivery Carrier for Phytobioactive Compounds as a Therapeutic Modulator for Targeting Mitochondrial Dysfunction in the Management of Neurodegenerative Diseases. Curr Neuropharmacol 2024; 22:1110-1128. [PMID: 36237157 PMCID: PMC10964109 DOI: 10.2174/1570159x20666221012142247] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2022] [Revised: 09/29/2022] [Accepted: 10/06/2022] [Indexed: 11/22/2022] Open
Abstract
Neurodegenerative disease (ND) is the fourth leading cause of death worldwide, with limited symptomatic therapies. Mitochondrial dysfunction is a major risk factor in the progression of ND, and it-increases the generation of reactive oxygen species (ROS). Overexposure to these ROS induces apoptotic changes leading to neuronal cell death. Many studies have shown the prominent effect of phytobioactive compounds in managing mitochondrial dysfunctions associated with ND, mainly due to their antioxidant properties. The drug delivery to the brain is limited due to the presence of the blood-brain barrier (BBB), but effective drug concentration needs to reach the brain for the therapeutic action. Therefore, developing safe and effective strategies to enhance drug entry in the brain is required to establish ND's treatment. The microneedle-based drug delivery system is one of the effective non-invasive techniques for drug delivery through the transdermal route. Microneedles are micronsized drug delivery needles that are self-administrable. It can penetrate through the stratum corneum skin layer without hitting pain receptors, allowing the phytobioactive compounds to be released directly into systemic circulation in a controlled manner. With all of the principles mentioned above, this review discusses microneedles as a versatile drug delivery carrier for the phytoactive compounds as a therapeutic potentiating agent for targeting mitochondrial dysfunction for the management of ND.
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Affiliation(s)
- Akshay Bandiwadekar
- Department of Pharmaceutics, NGSM Institute of Pharmaceutical Sciences, NITTE (Deemed-to-be University), Mangalore, 575018, India
| | - Kartik Bhairu Khot
- Department of Pharmaceutics, NGSM Institute of Pharmaceutical Sciences, NITTE (Deemed-to-be University), Mangalore, 575018, India
| | - Gopika Gopan
- Department of Pharmaceutics, NGSM Institute of Pharmaceutical Sciences, NITTE (Deemed-to-be University), Mangalore, 575018, India
| | - Jobin Jose
- Department of Pharmaceutics, NGSM Institute of Pharmaceutical Sciences, NITTE (Deemed-to-be University), Mangalore, 575018, India
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17
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Cai H, Liu D, Xue WW, Ma L, Xie HT, Ning K. Lipid-based nanoparticles for drug delivery in Parkinson's disease. Transl Neurosci 2024; 15:20220359. [PMID: 39654878 PMCID: PMC11627081 DOI: 10.1515/tnsci-2022-0359] [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: 05/22/2024] [Revised: 10/01/2024] [Accepted: 10/07/2024] [Indexed: 12/12/2024] Open
Abstract
Parkinson's disease (PD) is a neurodegenerative disorder that predominantly affects dopaminergic neurons in the substantia nigra and ventral tegmental area, resulting in symptoms such as tremors, muscle rigidity, bradykinesia, and potential cognitive and affective disturbances. The effective delivery of pharmacological agents to the central nervous system is hindered by various factors, including the restrictive properties of the blood‒brain barrier and blood‒spinal cord barrier, as well as the physicochemical characteristics of the drugs. Traditional drug delivery methods may not provide the therapeutic concentrations necessary for functional restoration in PD patients. However, lipid-based nanoparticles (NPs) offer new possibilities for enhancing the bioavailability of established treatment regimens and developing innovative therapies that can modify the course of the disease. This review provides a concise overview of recent advances in lipid-based NP strategies aimed at mitigating specific pathological mechanisms relevant to PD progression. This study also explores the potential applications of nanotechnological innovations in the development of advanced treatment modalities for individuals with PD.
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Affiliation(s)
- Han Cai
- Guangdong Celconta Biotechnology Co., Ltd, 9 Xincheng Road, Songshan Lake Park, Dongguan, Guangdong, PR China
| | - Dong Liu
- Guangdong Celconta Biotechnology Co., Ltd, 9 Xincheng Road, Songshan Lake Park, Dongguan, Guangdong, PR China
| | - Wei-Wei Xue
- Guangdong Celconta Biotechnology Co., Ltd, 9 Xincheng Road, Songshan Lake Park, Dongguan, Guangdong, PR China
- School of Biological Engineering, Dalian Polytechnic University, Dalian, 116034, China
| | - Liya Ma
- Guangdong Celconta Biotechnology Co., Ltd, 9 Xincheng Road, Songshan Lake Park, Dongguan, Guangdong, PR China
| | - Hai-Tao Xie
- Guangdong Celconta Biotechnology Co., Ltd, 9 Xincheng Road, Songshan Lake Park, Dongguan, Guangdong, PR China
| | - Ke Ning
- Guangdong Celconta Biotechnology Co., Ltd, 9 Xincheng Road, Songshan Lake Park, Dongguan, Guangdong, PR China
- Sheffield Institute of Translational Neuroscience (SITraN), University of Sheffield, Sheffield, United Kingdom
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18
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Hasnain M, Kanwal T, Rehman K, Rehman SRU, Aslam S, Roome T, Perveen S, Zaidi MB, Saifullah S, Yasmeen S, Hasan A, Shah MR. Microarray needles comprised of arginine-modified chitosan/PVA hydrogel for enhanced antibacterial and wound healing potential of curcumin. Int J Biol Macromol 2023; 253:126697. [PMID: 37673138 DOI: 10.1016/j.ijbiomac.2023.126697] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2023] [Revised: 09/01/2023] [Accepted: 09/02/2023] [Indexed: 09/08/2023]
Abstract
Wound healing is a multifaceted and complex process that includes inflammation, hemostasis, remodeling, and granulation. Failures in any link may cause the healing process to be delayed. As a result, wound healing has always been a main research focus across the entire medical field, posing significant challenges and financial burdens. Hence, the current investigation focused on the design and development of arginine-modified chitosan/PVA hydrogel-based microneedles (MNs) as a curcumin (CUR) delivery system for improved wound healing and antibacterial activity. The substrate possesses exceptional swelling capabilities that allow tissue fluid from the wound to be absorbed, speeding up wound closure. The antibacterial activity of MNs was investigated against S. aureus and E. coli. The results revealed that the developed CUR-loaded MNs had increased antioxidant activity and sustained drug release behavior. Furthermore, after being loaded in the developed MNs, it revealed improved antibacterial activity of CUR. Wound healing potential was assessed by histopathological analysis and wound closure%. The observed results suggest that the CUR-loaded MNs greatly improved wound healing potential via tissue regeneration and collagen deposition, demonstrating the potential of developed MNs patches to be used as an effective carrier for wound healing in healthcare settings.
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Affiliation(s)
- Muhammad Hasnain
- H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan
| | - Tasmina Kanwal
- H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan
| | - Khadija Rehman
- H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan.
| | - Syed Raza Ur Rehman
- Mechanical and Industrial Engineering, Qatar University, 2713, Doha, Qatar; Biomedical Research Center, Qatar University, 2713, Doha, Qatar.
| | - Shazmeen Aslam
- Dow Institute for Advanced Biological and Animal Research, Dow International Medical College, Dow University of Health Sciences, Karachi 74200, Pakistan.
| | - Talat Roome
- Dow Institute for Advanced Biological and Animal Research, Dow International Medical College, Dow University of Health Sciences, Karachi 74200, Pakistan; Molecular Pathology Section, Department of Pathology, Dow Diagnostic Reference and Research Laboratory, Dow University of Health Sciences, Karachi 74200, Pakistan.
| | - Samina Perveen
- School of Environmental and Biological Engineering, Nanjing University of Science and Technology, Nanjing, PR China
| | - Midhat Batool Zaidi
- Dow Institute for Advanced Biological and Animal Research, Dow International Medical College, Dow University of Health Sciences, Karachi 74200, Pakistan.
| | - Salim Saifullah
- H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan; Pakistan Forest Institute Peshawar, Pakistan
| | - Saira Yasmeen
- H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan
| | - Anwarul Hasan
- Mechanical and Industrial Engineering, Qatar University, 2713, Doha, Qatar; Biomedical Research Center, Qatar University, 2713, Doha, Qatar
| | - Muhammad Raza Shah
- H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan.
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19
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Burns J, Buck AC, D’ Souza S, Dube A, Bardien S. Nanophytomedicines as Therapeutic Agents for Parkinson's Disease. ACS OMEGA 2023; 8:42045-42061. [PMID: 38024675 PMCID: PMC10652730 DOI: 10.1021/acsomega.3c04862] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/06/2023] [Revised: 09/11/2023] [Accepted: 10/06/2023] [Indexed: 12/01/2023]
Abstract
Phytochemicals are promising therapeutics for various neurodegenerative disorders, including Parkinson's disease (PD). However, their efficacy, pharmacokinetic properties, and penetration across the blood-brain barrier can be improved using delivery systems such as nanoparticles. We reviewed recently published work in which nanoparticles were used to deliver phytochemicals toward PD treatment. The studies show that nanoparticles not only improve the pharmacological effect of the phytochemicals but also enable targeting to the brain and crossing of the blood-brain barrier. Various ligands were added to the nanoparticles to improve blood-brain barrier transportation. The promising findings from the published studies reveal that more research into nanophytomedicine approaches as therapeutic targets for PD is warranted, especially since they have the potential to protect against key features of PD, including α-synuclein aggregation, mitochondrial dysfunction, and dopaminergic neuronal death. Furthermore, future directions should involve smart designs to tailor nanoparticles for improved therapeutic delivery by modifying their features, such as architecture, surface and material properties, targeting ligands, and responsiveness.
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Affiliation(s)
- Jessica Burns
- Division
of Molecular Biology and Human Genetics, Faculty of Medicine and Health
Sciences, Stellenbosch University, Stellenbosch, Cape Town 7600, South Africa
| | - Amy Claire Buck
- Division
of Molecular Biology and Human Genetics, Faculty of Medicine and Health
Sciences, Stellenbosch University, Stellenbosch, Cape Town 7600, South Africa
| | - Sarah D’ Souza
- School
of Pharmacy, University of the Western Cape, Bellville, Cape Town 7535, South Africa
| | - Admire Dube
- School
of Pharmacy, University of the Western Cape, Bellville, Cape Town 7535, South Africa
| | - Soraya Bardien
- Division
of Molecular Biology and Human Genetics, Faculty of Medicine and Health
Sciences, Stellenbosch University, Stellenbosch, Cape Town 7600, South Africa
- South
African Medical Research Council/Stellenbosch University Genomics
of Brain Disorders Research Unit, Stellenbosch
University, Stellenbosch, Cape Town 7600, South Africa
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20
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Lv H, Gao N, Zhou Q, Wang Y, Ling G, Zhang P. Collagen-Based Dissolving Microneedles with Flexible Pedestals: A Transdermal Delivery System for Both Anti-Aging and Skin Diseases. Adv Healthc Mater 2023; 12:e2203295. [PMID: 37029522 DOI: 10.1002/adhm.202203295] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2022] [Revised: 03/19/2023] [Indexed: 04/09/2023]
Abstract
Biocompatible polymer microneedles (MNs) are emerging as a promising platform for transdermal drug delivery, especially for facial treatments. Therefore, an MN patch in this study uses hydrolyzed collagen (HC) contained in skin cells as the main raw material and adopts a two-step cast method to develop a rapidly dissolving microneedle (DMN) to deliver collagen in a simple and minimally invasive way, allowing the release of the encapsulated drug in the skin. By optimizing the formulation and proportion of HC and auxiliary support materials, the mechanical strength required to pierce the skin is obtained, while the soft pedestal allows for flexibility in application. The DMNs can dissolve completely in the skin within 15 min and release within ≈ 8 h, and do not cause toxicity or irritation when being applied. In contrast to the ineffectiveness of oral and external application, and the high risk of dermal injection, drug-loaded DMNs overcome the drawbacks of traditional methods with direct penetration and minimally invasive manner, enabling efficient and safe treatment. The successful preparation and research of HC DMNs have innovative and practical significance in this field, and it is expected to become a simple, effective, and popular transdermal drug delivery platform for cosmetics.
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Affiliation(s)
- Hongqian Lv
- Wuya College of Innovation, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, 110016, China
| | - Nan Gao
- Wuya College of Innovation, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, 110016, China
| | - Qixin Zhou
- Wuya College of Innovation, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, 110016, China
| | - Yan Wang
- Wuya College of Innovation, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, 110016, China
| | - Guixia Ling
- Wuya College of Innovation, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, 110016, China
| | - Peng Zhang
- Wuya College of Innovation, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, 110016, China
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21
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van Vliet EF, Knol MJ, Schiffelers RM, Caiazzo M, Fens MHAM. Levodopa-loaded nanoparticles for the treatment of Parkinson's disease. J Control Release 2023; 360:212-224. [PMID: 37343725 DOI: 10.1016/j.jconrel.2023.06.026] [Citation(s) in RCA: 20] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2022] [Revised: 06/15/2023] [Accepted: 06/18/2023] [Indexed: 06/23/2023]
Abstract
Parkinson's disease (PD) is a neurodegenerative disorder characterized by degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc) resulting in dopamine (DA) deficiency, which manifests itself in motor symptoms including tremors, rigidity and bradykinesia. Current PD treatments aim at symptom reduction through oral delivery of levodopa (L-DOPA), a precursor of DA. However, L-DOPA delivery to the brain is inefficient and increased dosages are required as the disease progresses, resulting in serious side effects like dyskinesias. To improve PD treatment efficacy and to reduce side effects, recent research focuses on the encapsulation of L-DOPA into polymeric- and lipid-based nanoparticles (NPs). These formulations can protect L-DOPA from systemic decarboxylation into DA and improve L-DOPA delivery to the central nervous system. Additionally, NPs can be modified with proteins, peptides and antibodies specifically targeting the blood-brain barrier (BBB), thereby reducing required dosages and free systemic DA. Alternative delivery approaches for NP-encapsulated L-DOPA include intravenous (IV) administration, transdermal delivery using adhesive patches and direct intranasal administration, facilitating increased therapeutic DA concentrations in the brain. This review provides an overview of the recent advances for NP-mediated L-DOPA delivery to the brain, and debates challenges and future perspectives on the field.
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Affiliation(s)
- Emile F van Vliet
- Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 3584 CG Utrecht, the Netherlands
| | - Maarten J Knol
- Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 3584 CG Utrecht, the Netherlands
| | | | - Massimiliano Caiazzo
- Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 3584 CG Utrecht, the Netherlands; Department of Molecular Medicine and Medical Biotechnology, University of Naples "Federico II", Via Pansini 5, 80131 Naples, Italy.
| | - Marcel H A M Fens
- Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 3584 CG Utrecht, the Netherlands.
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22
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Isopencu GO, Covaliu-Mierlă CI, Deleanu IM. From Plants to Wound Dressing and Transdermal Delivery of Bioactive Compounds. PLANTS (BASEL, SWITZERLAND) 2023; 12:2661. [PMID: 37514275 PMCID: PMC10386126 DOI: 10.3390/plants12142661] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/17/2023] [Revised: 07/10/2023] [Accepted: 07/14/2023] [Indexed: 07/30/2023]
Abstract
Transdermal delivery devices and wound dressing materials are constantly improved and upgraded with the aim of enhancing their beneficial effects, biocompatibility, biodegradability, and cost effectiveness. Therefore, researchers in the field have shown an increasing interest in using natural compounds as constituents for such systems. Plants, as an important source of so-called "natural products" with an enormous variety and structural diversity that still exceeds the capacity of present-day sciences to define or even discover them, have been part of medicine since ancient times. However, their benefits are just at the beginning of being fully exploited in modern dermal and transdermal delivery systems. Thus, plant-based primary compounds, with or without biological activity, contained in gums and mucilages, traditionally used as gelling and texturing agents in the food industry, are now being explored as valuable and cost-effective natural components in the biomedical field. Their biodegradability, biocompatibility, and non-toxicity compensate for local availability and compositional variations. Also, secondary metabolites, classified based on their chemical structure, are being intensively investigated for their wide pharmacological and toxicological effects. Their impact on medicine is highlighted in detail through the most recent reported studies. Innovative isolation and purification techniques, new drug delivery devices and systems, and advanced evaluation procedures are presented.
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Affiliation(s)
- Gabriela Olimpia Isopencu
- Department of Chemical and Biochemical Engineering, University Politehnica of Bucharest, Polizu Str. 1-7, 011061 Bucharest, Romania
| | - Cristina-Ileana Covaliu-Mierlă
- Department of Biotechnical Systems, Faculty of Biotechnical Systems Engineering, University Politehnica of Bucharest, 313 Splaiul Independentei, 060042 Bucharest, Romania
| | - Iuliana-Mihaela Deleanu
- Department of Chemical and Biochemical Engineering, University Politehnica of Bucharest, Polizu Str. 1-7, 011061 Bucharest, Romania
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23
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Gopan G, Jose J, Khot KB, Bandiwadekar A. The use of cellulose, chitosan and hyaluronic acid in transdermal therapeutic management of obesity: A review. Int J Biol Macromol 2023:125374. [PMID: 37330096 DOI: 10.1016/j.ijbiomac.2023.125374] [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: 02/03/2023] [Revised: 05/29/2023] [Accepted: 06/11/2023] [Indexed: 06/19/2023]
Abstract
Obesity is a clinical condition with rising popularity and detrimental impacts on human health. According to the World Health Organization, obesity is the sixth most common cause of death worldwide. It is challenging to combat obesity because medications that are successful in the clinical investigation have harmful side effects when administered orally. The conventional approaches for treating obesity primarily entail synthetic compounds and surgical techniques but possess severe adverse effects and recurrences. As a result, a safe and effective strategy to combat obesity must be initiated. Recent studies have shown that biological macromolecules of the carbohydrate class, such as cellulose, hyaluronic acid, and chitosan, can enhance the release and efficacy of medications for obesity but due to their short biological half-lives and poor oral bioavailability, their distribution rate is affected. This helps to comprehend the need for an effective therapeutic approach via a transdermal drug delivery system. This review focuses on the transdermal administration, utilizing cellulose, chitosan, and hyaluronic acid via microneedles, as it offers a promising solution to overcome existing therapy limitations in managing obesity and it also highlights how microneedles can effectively deliver therapeutic substances through the skin's outer layer, bypassing pain receptors and specifically targeting adipose tissue.
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Affiliation(s)
- Gopika Gopan
- NITTE Deemed-to-be University, NGSM Institute of Pharmaceutical Sciences, Department of Pharmaceutics, Mangalore 575018, India
| | - Jobin Jose
- NITTE Deemed-to-be University, NGSM Institute of Pharmaceutical Sciences, Department of Pharmaceutics, Mangalore 575018, India.
| | - Kartik Bhairu Khot
- NITTE Deemed-to-be University, NGSM Institute of Pharmaceutical Sciences, Department of Pharmaceutics, Mangalore 575018, India
| | - Akshay Bandiwadekar
- NITTE Deemed-to-be University, NGSM Institute of Pharmaceutical Sciences, Department of Pharmaceutics, Mangalore 575018, India
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24
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Guillot AJ, Martínez-Navarrete M, Zinchuk-Mironova V, Melero A. Microneedle-assisted transdermal delivery of nanoparticles: Recent insights and prospects. WILEY INTERDISCIPLINARY REVIEWS. NANOMEDICINE AND NANOBIOTECHNOLOGY 2023:e1884. [PMID: 37041036 DOI: 10.1002/wnan.1884] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/26/2022] [Revised: 02/01/2023] [Accepted: 02/13/2023] [Indexed: 04/13/2023]
Abstract
Transdermal delivery of drugs offers an interesting alternative for the administration of molecules that present certain troubles when delivered by the oral route. It can produce systemic effects or perform a local action when the formulation exerts an optimal controlled drug release or a targeted delivery to the specific cell type or site. It also avoids several inconveniences of the oral administration such as the hepatic first pass effect, gastric pH-induced hydrolysis, drug malabsorption because of certain diseases or surgeries, and unpleasant organoleptic properties. Nanomedicine and microneedle array patches (MAPs) are two of the trendiest delivery systems applied to transdermal research nowadays. However, the skin is a protective barrier and nanoparticles (NPs) cannot pass through the intact stratum corneum. The association of NPs and MAPs (NPs@MAPs) work synergistically, since MAPs assist NPs to bypass the outer skin layers, and NPs contribute to the system providing controlled drug release and targeted delivery. Vaccination and tailored therapies have been proposed as fields where both NPs and MAPs have great potential due to inherent characteristics. MAPs conception and easy use could allow self-administration and therefore facilitate mass vaccination campaigns in undeveloped areas with weak healthcare services. Additionally, nanomedicine is being explored as a platform to personalize therapies in such an important field as oncology. In this work we show recent insights that prove the benefits of NPs@MAPs association and analyze the prospects and the discrete interest of the industry in NPs@MAPs, evaluating different limiting steps that restricts NPs@MAPs translation to the clinical practice. This article is categorized under: Nanotechnology Approaches to Biology > NA Therapeutic Approaches and Drug Discovery > NA.
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Affiliation(s)
- Antonio José Guillot
- Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Valencia, Av. Vicent Andrés Estelles s/n, 46100, Burjassot, Spain
| | - Miquel Martínez-Navarrete
- Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Valencia, Av. Vicent Andrés Estelles s/n, 46100, Burjassot, Spain
| | - Valeria Zinchuk-Mironova
- Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Valencia, Av. Vicent Andrés Estelles s/n, 46100, Burjassot, Spain
| | - Ana Melero
- Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Valencia, Av. Vicent Andrés Estelles s/n, 46100, Burjassot, Spain
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25
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Prabahar K, Uthumansha U, Elsherbiny N, Qushawy M. Enhanced Skin Permeation and Controlled Release of β-Sitosterol Using Cubosomes Encrusted with Dissolving Microneedles for the Management of Alopecia. Pharmaceuticals (Basel) 2023; 16:ph16040563. [PMID: 37111320 PMCID: PMC10142597 DOI: 10.3390/ph16040563] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2023] [Revised: 04/02/2023] [Accepted: 04/05/2023] [Indexed: 04/29/2023] Open
Abstract
The use of synthetic medication for treating alopecia is restricted because of systemic exposure and related negative effects. Beta-sitosterol (β-ST), a natural chemical, has lately been studied for its potential to promote hair development. The cubosomes with dissolving microneedles (CUBs-MND) created in this study may be a useful starting point for the creation of a sophisticated dermal delivery system for β-ST. Cubosomes (CUBs) were prepared by the emulsification method, using glyceryl monooleate (GMO) as a lipid polymer. CUBs were loaded with dissolving microneedles (MND) fabricated with HA and a PVP-K90 matrix. An ex vivo skin permeation study and an in vivo hair growth efficacy test of β-ST were performed with both CUB and CUB-MND. The average particle size of the CUBs was determined to be 173.67 ± 0.52 nm, with a low polydispersity index (0.3) and a high zeta potential value that prevents the aggregate formation of dispersed particles. When compared to CUBs alone, CUBs-MND displayed higher permeating levels of β-ST at all-time points. In the animals from the CUB-MND group, significant hair development was observed. According to the results of the current investigation, CUBs that integrate dissolving microneedles of β-ST are superior in terms of transdermal skin penetration and activity for the treatment of alopecia.
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Affiliation(s)
- Kousalya Prabahar
- Department of Pharmacy Practice, Faculty of Pharmacy, University of Tabuk, Tabuk 71491, Saudi Arabia
| | - Ubaidulla Uthumansha
- Department of Pharmaceutics, Crescent School of Pharmacy, B.S. Abdur Rahman Crescent Institute of Science and Technology, Chennai 600048, India
| | - Nehal Elsherbiny
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Tabuk, Tabuk 71491, Saudi Arabia
- Department of Biochemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt
| | - Mona Qushawy
- Department of Pharmaceutics, Faculty of Pharmacy, University of Tabuk, Tabuk 71491, Saudi Arabia
- Department of Pharmaceutics, Faculty of Pharmacy, Sinai University, Alarish 45511, North Sinai, Egypt
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26
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Nawaz A, Latif MS, Shah MKA, Elsayed TM, Ahmad S, Khan HA. Formulation and Characterization of Ethyl Cellulose-Based Patches Containing Curcumin-Chitosan Nanoparticles for the Possible Management of Inflammation via Skin Delivery. Gels 2023; 9:gels9030201. [PMID: 36975650 PMCID: PMC10048031 DOI: 10.3390/gels9030201] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2023] [Revised: 02/28/2023] [Accepted: 03/03/2023] [Indexed: 03/09/2023] Open
Abstract
Curcumin, a natural phenolic compound, exhibits poor absorption and extensive first pass metabolism after oral administration. In the present study, curcumin-chitosan nanoparticles (cur-cs-np) were prepared and incorporated into ethyl cellulose patches for the management of inflammation via skin delivery. Ionic gelation method was used for the preparation of nanoparticles. The prepared nanoparticles were evaluated for size, zetapotential, surface morphology, drug content, and % encapsulation efficiency. The nanoparticles were then incorporated into ethyl cellulose-based patches using solvent evaporation technique. ATR-FTIR was used to study/assess incompatibility between drug and excipients. The prepared patches were evaluated physiochemically. The in vitro release, ex vivo permeation, and skin drug retention studies were carried out using Franz diffusion cells and rat skin as permeable membrane. The prepared nanoparticles were spherical, with particle size in the range of 203–229 nm, zetapotential 25–36 mV, and PDI 0.27–0.29 Mw/Mn. The drug content and %EE were 53% and 59%. Nanoparticles incorporated patches are smooth, flexible, and homogenous. The in vitro release and ex vivo permeation of curcumin from nanoparticles were higher than the patches, whereas the skin retention of curcumin was significantly higher in case of patches. The developed patches deliver cur-cs-np into the skin, where nanoparticles interact with skin negative charges and hence result in higher and prolonged retention in the skin. The higher concentration of drug in the skin helps in better management of inflammation. This was shown by anti-inflammatory activity. The inflammation (volume of paw) was significantly reduced when using patches as compared to nanoparticles. It was concluded that the incorporation of cur-cs-np into ethyl cellulose-based patches results in controlled release and hence enhanced anti-inflammatory activity.
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Affiliation(s)
- Asif Nawaz
- Advanced Drug Delivery Lab, Gomal Centre of Pharmaceutical Sciences, Faculty of Pharmacy, Gomal University, Dera Ismail Khan 29050, Pakistan
- Correspondence:
| | - Muhammad Shahid Latif
- Advanced Drug Delivery Lab, Gomal Centre of Pharmaceutical Sciences, Faculty of Pharmacy, Gomal University, Dera Ismail Khan 29050, Pakistan
| | - Muhammad Khurshid Alam Shah
- Advanced Drug Delivery Lab, Gomal Centre of Pharmaceutical Sciences, Faculty of Pharmacy, Gomal University, Dera Ismail Khan 29050, Pakistan
| | - Tarek M. Elsayed
- Pharmaceutical Technology Department, Faculty of Pharmacy, Sultan Zainal Abidin University, Besut Kampus, Besut 22200, Malaysia
| | - Saeed Ahmad
- Institute of Biotechnology and Microbiology, Bacha Khan University, Charsadda 24420, Pakistan
| | - Hamid Ali Khan
- Directorate of ORIC, Bacha Khan University, Charsadda 24420, Pakistan
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27
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Intranasal Polymeric and Lipid-Based Nanocarriers for CNS Drug Delivery. Pharmaceutics 2023; 15:pharmaceutics15030746. [PMID: 36986607 PMCID: PMC10051709 DOI: 10.3390/pharmaceutics15030746] [Citation(s) in RCA: 29] [Impact Index Per Article: 14.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2023] [Revised: 02/14/2023] [Accepted: 02/16/2023] [Indexed: 02/25/2023] Open
Abstract
Nanomedicine is currently focused on the design and development of nanocarriers that enhance drug delivery to the brain to address unmet clinical needs for treating neuropsychiatric disorders and neurological diseases. Polymer and lipid-based drug carriers are advantageous for delivery to the central nervous system (CNS) due to their safety profiles, drug-loading capacity, and controlled-release properties. Polymer and lipid-based nanoparticles (NPs) are reported to penetrate the blood–brain barrier (BBB) and have been extensively assessed in in vitro and animal models of glioblastoma, epilepsy, and neurodegenerative disease. Since approval by the Food and Drug Administration (FDA) of intranasal esketamine for treatment of major depressive disorder, intranasal administration has emerged as an attractive route to bypass the BBB for drug delivery to the CNS. NPs can be specifically designed for intranasal administration by tailoring their size and coating with mucoadhesive agents or other moieties that promote transport across the nasal mucosa. In this review, unique characteristics of polymeric and lipid-based nanocarriers desirable for drug delivery to the brain are explored in addition to their potential for drug repurposing for the treatment of CNS disorders. Progress in intranasal drug delivery using polymeric and lipid-based nanostructures for the development of treatments of various neurological diseases are also described.
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28
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Khot KB, Gopan G, Bandiwadekar A, Jose J. Current advancements related to phytobioactive compounds based liposomal delivery for neurodegenerative diseases. Ageing Res Rev 2023; 83:101806. [PMID: 36427765 DOI: 10.1016/j.arr.2022.101806] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2022] [Revised: 11/17/2022] [Accepted: 11/20/2022] [Indexed: 11/24/2022]
Abstract
Neurodegenerative diseases are the most widely affected disease condition in an aging population. The treatment available reduces the elevated manifestations but is ineffective due to the drug's poor bioavailability, plasma stability, and permeability across the blood-brain barrier (BBB). Until now, no therapeutic compound has been able to stop the progression of neurodegenerative disease. Even the available therapeutic moiety manages it with possible adverse effects up to the later stage. Hence, phytobioactive compounds of plant origin offer effective treatment strategies against neurodegenerative diseases. The only difficulty of these phytobioactive compounds is permeability across the BBB. Engineered nanocarriers such as liposomes provide high lipid permeability across BBB. Liposomes have unique physicochemical properties that are widely investigated for their application in diagnosing and treating neurodegenerative diseases. The surface modification on liposomes by peptides, antibodies, and RNA aptamers offers receptor targeting. These brain-targeted approaches by liposomes improve the efficacy of phytoconstituents. Additional surface modification methods are utilized on liposomes, which increases the brain-targeted delivery of phytobioactive compounds. The marketing strategy of the liposomal delivery system is in its peak mode, where it has the potential to modify the existing therapy. This review will summarize the brain target liposomal delivery of phytobioactive compounds as a novel disease-modifying agent for treating neurodegenerative diseases.
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Affiliation(s)
- Kartik Bhairu Khot
- NITTE (Deemed to be University), NGSM Institute of Pharmaceutical Sciences, Department of Pharmaceutics, Mangalore 575018, India
| | - Gopika Gopan
- NITTE (Deemed to be University), NGSM Institute of Pharmaceutical Sciences, Department of Pharmaceutics, Mangalore 575018, India
| | - Akshay Bandiwadekar
- NITTE (Deemed to be University), NGSM Institute of Pharmaceutical Sciences, Department of Pharmaceutics, Mangalore 575018, India
| | - Jobin Jose
- NITTE (Deemed to be University), NGSM Institute of Pharmaceutical Sciences, Department of Pharmaceutics, Mangalore 575018, India.
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29
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Improved Topical Drug Delivery: Role of Permeation Enhancers and Advanced Approaches. Pharmaceutics 2022; 14:pharmaceutics14122818. [PMID: 36559311 PMCID: PMC9785322 DOI: 10.3390/pharmaceutics14122818] [Citation(s) in RCA: 54] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2022] [Revised: 11/10/2022] [Accepted: 11/15/2022] [Indexed: 12/23/2022] Open
Abstract
The delivery of drugs via transdermal routes is an attractive approach due to ease of administration, bypassing of the first-pass metabolism, and the large skin surface area. However, a major drawback is an inability to surmount the skin's stratum corneum (SC) layer. Therefore, techniques reversibly modifying the stratum corneum have been a classical approach. Surmounting the significant barrier properties of the skin in a well-organised, momentary, and harmless approach is still challenging. Chemical permeation enhancers (CPEs) with higher activity are associated with certain side effects restricting their advancement in transdermal drug delivery. Furthermore, complexity in the interaction of CPEs with the skin has led to difficulty in elucidating the mechanism of action. Nevertheless, CPEs-aided transdermal drug delivery will accomplish its full potential due to advancements in analytical techniques, synthetic chemistry, and combinatorial studies. This review focused on techniques such as drug-vehicle interaction, vesicles and their analogues, and novel CPEs such as lipid synthesis inhibitors (LSIs), cell-penetrating peptides (CPPs), and ionic liquids (ILs). In addition, different types of microneedles, including 3D-printed microneedles, have been focused on in this review.
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30
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Niu J, Yuan M, Liu Y, Wang L, Tang Z, Wang Y, Qi Y, Zhang Y, Ya H, Fan Y. Silk peptide-hyaluronic acid based nanogels for the enhancement of the topical administration of curcumin. Front Chem 2022; 10:1028372. [PMID: 36199664 PMCID: PMC9527322 DOI: 10.3389/fchem.2022.1028372] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2022] [Accepted: 09/05/2022] [Indexed: 11/16/2022] Open
Abstract
The present study focused on the development of Cur-loaded SOHA nanogels (Cur-SHNGs) to enhance the topical administration of Cur. The physiochemical properties of Cur-SHNGs were characterized. Results showed that the morphology of the Cur-SHNGs was spherical, the average size was 171.37 nm with a zeta potential of −13.23 mV. Skin permeation experiments were carried out using the diffusion cell systems. It was found that the skin retention of Cur-SHNGs was significantly improved since it showed the best retention value (0.66 ± 0.17 μg/cm2). In addition, the hematoxylin and eosin staining showed that the Cur-SHNGs improved transdermal drug delivery by altering the skin microstructure. Fluorescence imaging indicated that Cur-SHNGs could effectively deliver the drug to the deeper layers of the skin. Additionally, Cur-SHNGs showed significant analgesic and anti-inflammatory activity with no skin irritation. Taken together, Cur-SHNGs could be effectively used for the topical delivery of therapeutic drugs.
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Affiliation(s)
- Jiangxiu Niu
- College of Food and Drug, Henan Functional Cosmetics Engineering and Technology Research Center, Luoyang Normal University, Luoyang, Henan, China
| | - Ming Yuan
- College of Food and Drug, Henan Functional Cosmetics Engineering and Technology Research Center, Luoyang Normal University, Luoyang, Henan, China
| | - Yao Liu
- College of Food and Drug, Henan Functional Cosmetics Engineering and Technology Research Center, Luoyang Normal University, Luoyang, Henan, China
| | - Liye Wang
- College of Food and Drug, Henan Functional Cosmetics Engineering and Technology Research Center, Luoyang Normal University, Luoyang, Henan, China
- *Correspondence: Liye Wang, ; Zigui Tang, ; Huiyuan Ya,
| | - Zigui Tang
- Department of Pharmacy, Henan Medical College, Zhengzhou, China
- *Correspondence: Liye Wang, ; Zigui Tang, ; Huiyuan Ya,
| | - Yihan Wang
- College of Food and Drug, Henan Functional Cosmetics Engineering and Technology Research Center, Luoyang Normal University, Luoyang, Henan, China
| | - Yueheng Qi
- College of Food and Drug, Henan Functional Cosmetics Engineering and Technology Research Center, Luoyang Normal University, Luoyang, Henan, China
| | | | - Huiyuan Ya
- College of Food and Drug, Henan Functional Cosmetics Engineering and Technology Research Center, Luoyang Normal University, Luoyang, Henan, China
- *Correspondence: Liye Wang, ; Zigui Tang, ; Huiyuan Ya,
| | - Yanli Fan
- College of Food and Drug, Henan Functional Cosmetics Engineering and Technology Research Center, Luoyang Normal University, Luoyang, Henan, China
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31
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Joy D, Jose J, Bibi S, Bandiwadekar A, Gopan G, Mariana Gonçalves Lima C, Bin Emran T, A. Alhumaydhi F, Ashtekar H, D. S S, Adam Conte-Junior C. Development of Microneedle Patch Loaded with Bacopa monnieri Solid Lipid Nanoparticles for the Effective Management of Parkinson's Disease. Bioinorg Chem Appl 2022; 2022:9150205. [PMID: 35992047 PMCID: PMC9385340 DOI: 10.1155/2022/9150205] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2022] [Accepted: 07/01/2022] [Indexed: 11/17/2022] Open
Abstract
The demand for drug delivery systems (DDS) to treat Parkinson's disease (PD) is still high, and microneedle (MN) assisted transdermal DDS offers enormous potential. Herbal products for PD have been shown to have antioxidant effects in reducing dopaminergic neurons from degeneration. Here, we attempted to incorporate solid lipid nanoparticles (SLNs) of Bacopa monnieri into dissolvable microneedle arrays and evaluate its neuroprotective activity. The bloodless and painless microneedle arrays through the transdermal route deliver the drug across the blood-brain barrier at the desired concentration. The quality by design (QbD) approach was employed for optimizing the SLNs formulations. The mechanical strength, in vitro release studies, ex-vivo permeation investigation, skin irritation test, histopathological studies, biochemical studies, and behavioural tests SLNs loaded microneedle arrays were performed. The microneedle patches obtained were shown to be mechanically robust and were also found to be nonirritant with a decreased degree of bradykinesia, high motor coordination, and balance ability. Compared to systemic delivery systems, such an MN method can achieve a considerably lower effective dose and allow long-term home-based treatment.
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Affiliation(s)
- Delna Joy
- NITTE Deemed-to-be University, NGSM Institute of Pharmaceutical Sciences, Department of Pharmaceutics, Mangalore 575018, India
| | - Jobin Jose
- NITTE Deemed-to-be University, NGSM Institute of Pharmaceutical Sciences, Department of Pharmaceutics, Mangalore 575018, India
| | - Shabana Bibi
- Yunnan Herbal Laboratory, College of Ecology and Environmental Sciences, Yunnan University, Kunming 650091, Yunnan, China
- Department of Biosciences, Shifa Tameer-e-Millat University, Islamabad, Pakistan
| | - Akshay Bandiwadekar
- NITTE Deemed-to-be University, NGSM Institute of Pharmaceutical Sciences, Department of Pharmaceutics, Mangalore 575018, India
| | - Gopika Gopan
- NITTE Deemed-to-be University, NGSM Institute of Pharmaceutical Sciences, Department of Pharmaceutics, Mangalore 575018, India
| | | | - Talha Bin Emran
- Department of Pharmacy, BGC Trust University Bangladesh, Chittagong 4381, Bangladesh
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka 1207, Bangladesh
| | - Fahad A. Alhumaydhi
- Department of Medical Laboratories, College of Applied Medical Sciences, Qassim University, Buraydah 52571, Saudi Arabia
| | - Harsha Ashtekar
- NITTE Deemed-to-be University, NGSM Institute of Pharmaceutical Sciences, Department of Pharmacology, Mangalore 575018, India
| | - Sandeep D. S
- NITTE Deemed-to-be University, NGSM Institute of Pharmaceutical Sciences, Department of Pharmaceutics, Mangalore 575018, India
| | - Carlos Adam Conte-Junior
- Center for Food Analysis (NAL), Technological Development Support Laboratory (LADETEC), Federal University of Rio de Janeiro (UFRJ), Cidade Universitária, Rio de Janeiro 21941-598, Brazil
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32
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Sivani BM, Azzeh M, Patnaik R, Pantea Stoian A, Rizzo M, Banerjee Y. Reconnoitering the Therapeutic Role of Curcumin in Disease Prevention and Treatment: Lessons Learnt and Future Directions. Metabolites 2022; 12:metabo12070639. [PMID: 35888763 PMCID: PMC9320502 DOI: 10.3390/metabo12070639] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2022] [Revised: 06/30/2022] [Accepted: 07/08/2022] [Indexed: 02/04/2023] Open
Abstract
Turmeric is a plant with a very long history of medicinal use across different cultures. Curcumin is the active part of turmeric, which has exhibited various beneficial physiological and pharmacological effects. This review aims to critically appraise the corpus of literature associated with the above pharmacological properties of curcumin, with a specific focus on antioxidant, anti-inflammatory, anticancer and antimicrobial properties. We have also reviewed the different extraction strategies currently in practice, highlighting the strengths and drawbacks of each technique. Further, our review also summarizes the clinical trials that have been conducted with curcumin, which will allow the reader to get a quick insight into the disease/patient population of interest with the outcome that was investigated. Lastly, we have also highlighted the research areas that need to be further scrutinized to better grasp curcumin’s beneficial physiological and medicinal properties, which can then be translated to facilitate the design of better bioactive therapeutic leads.
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Affiliation(s)
- Bala Mohan Sivani
- Banerjee Research Group, College of Medicine and Health Sciences, Mohammed Bin Rashid University of Medicine and Health Sciences (MBRU), Dubai 505055, United Arab Emirates; (B.M.S.); (M.A.); (R.P.)
| | - Mahmoud Azzeh
- Banerjee Research Group, College of Medicine and Health Sciences, Mohammed Bin Rashid University of Medicine and Health Sciences (MBRU), Dubai 505055, United Arab Emirates; (B.M.S.); (M.A.); (R.P.)
| | - Rajashree Patnaik
- Banerjee Research Group, College of Medicine and Health Sciences, Mohammed Bin Rashid University of Medicine and Health Sciences (MBRU), Dubai 505055, United Arab Emirates; (B.M.S.); (M.A.); (R.P.)
| | - Anca Pantea Stoian
- Department of Diabetes, Nutrition and Metabolic Diseases, Carol Davila University of Medicine and Pharmacy, 020022 Bucharest, Romania;
| | - Manfredi Rizzo
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (Promise), University of Palermo, 90128 Palermo, Italy;
| | - Yajnavalka Banerjee
- Banerjee Research Group, College of Medicine and Health Sciences, Mohammed Bin Rashid University of Medicine and Health Sciences (MBRU), Dubai 505055, United Arab Emirates; (B.M.S.); (M.A.); (R.P.)
- Centre for Medical Education, University of Dundee, Dundee DD1 4HN, UK
- Correspondence: or ; Tel.: +971-527-873-636
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Madkhali OA. Perspectives and Prospective on Solid Lipid Nanoparticles as Drug Delivery Systems. Molecules 2022; 27:1543. [PMID: 35268643 PMCID: PMC8911793 DOI: 10.3390/molecules27051543] [Citation(s) in RCA: 37] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2022] [Revised: 02/15/2022] [Accepted: 02/22/2022] [Indexed: 01/02/2023] Open
Abstract
Combating multiple drug resistance necessitates the delivery of drug molecules at the cellular level. Novel drug delivery formulations have made it possible to improve the therapeutic effects of drugs and have opened up new possibilities for research. Solid lipid nanoparticles (SLNs), a class of colloidal drug carriers made of lipids, have emerged as potentially effective drug delivery systems. The use of SLNs is associated with numerous advantages such as low toxicity, high bioavailability of drugs, versatility in the incorporation of hydrophilic and lipophilic drugs, and the potential for production of large quantities of the carrier systems. The SLNs and nanostructured lipid carriers (NLCs) are the two most frequently used types of nanoparticles. These types of nanoparticles can be adjusted to deliver medications in specific dosages to specific tissues, while minimizing leakage and binding to non-target tissues.
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Affiliation(s)
- Osama A Madkhali
- Department of Pharmaceutics, College of Pharmacy, Jazan University, Jazan 45124, Saudi Arabia
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