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Nawaz A, Taj MB, Tasleem M, Ahmad Z, Ihsan A. Study of factors affecting cellulose derivatives composite in anticancer drug delivery: A comprehensive review. Int J Biol Macromol 2025; 310:143220. [PMID: 40250680 DOI: 10.1016/j.ijbiomac.2025.143220] [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: 03/22/2025] [Accepted: 04/14/2025] [Indexed: 04/20/2025]
Abstract
The targeted distribution of therapeutic molecules in cancer cells poses several challenges for biomedical applications. Drug delivery systems (DDS) are primarily designed to target cancer cells effectively to achieve maximum therapeutic effects. Cellulose is a well-known organic molecule owing to its biodegradability, biocompatibility, low toxicity, prolonged stability, and superior loading characteristics. However, cellulose composites have faced numerous drawbacks, such as higher molecular size, non-covalent interactions, poor mechanical strength, and limited water solubility. In contrast, cellulose derivatization has enhanced drug loading and release efficiency, improved mechanical strength, and mitigated drug solubility issues. This review summarized the recent advancement in cellulose-based composites such as DDS for cancer cell treatment and discussed responsive factors. The pH, temperature, magnetic nanoparticles, solubility, porosity, mechanical strength, nanoparticle size, increased time of drug release, crosslinking efficiency, etc., are major responsive assays that influence the therapeutic potential of anticancer drugs. Furthermore, overviewed the cellulose nanoformulations in sustained anticancer drug release and successfully illustrated the synthesizing methodologies as well as challenges in efficient DDS applications. Moreover, a brief overview of the interdisciplinary industrial uses of cellulose composites, including paper, textiles, and nanotechnology, is presented. Finally, cellulose-based composites provide a novel way of producing excellent DDS with enhanced therapeutic properties.
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Affiliation(s)
- Aamir Nawaz
- Institute of Chemistry, The Islamia University of Bahawalpur, Bahawalpur 63100, Pakistan
| | - Muhammad Babar Taj
- Institute of Chemistry, The Islamia University of Bahawalpur, Bahawalpur 63100, Pakistan.
| | - Muhammad Tasleem
- Department of Physics, University of Engineering and Technology, Lahore 54890, Pakistan
| | - Zia Ahmad
- Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China.
| | - Aaysha Ihsan
- College of Food Science and Engineering, Tianjin University of Science & Technology, Tianjin 300457, China
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2
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Zhao H, Zhou YY, Shan SR, Wu ZJ, Cao Y, Chen GY, Wu YM, Sun WK, Xia X, Yan H, Xu Y, Chen JL. A high-capacity combination of Pluronic L64-Cupping for intramuscular gene delivery. Int J Pharm 2025; 672:125366. [PMID: 39956407 DOI: 10.1016/j.ijpharm.2025.125366] [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: 10/10/2024] [Revised: 01/28/2025] [Accepted: 02/13/2025] [Indexed: 02/18/2025]
Abstract
Intramuscular injection of plasmid DNA (pDNA) is a promising approach for gene therapy, but its efficiency is hindered by both extracellular and intracellular barriers. The extracellular matrix (ECM), including collagens and nucleases, obstructs pDNA penetration, while intracellular challenges include crossing the plasma membrane, escaping endosomes, and reaching the nucleus. Though non-viral carriers like polymers and cationic lipids have been developed, they often fail to address both barriers simultaneously, leading to poor gene transfer in vivo. Physical methods exist but may damage tissues and cause patient discomfort. Here, we introduce a Pluronic L64-Cupping (L/C) gene delivery system that enhances pDNA delivery by sequentially overcoming ECM diffusion, membrane permeabilization, and intracellular transfection. After intramuscular injection of the pDNA-Pluronic L64 mixture, negative pressure is applied to the injection site, significantly boosting reporter gene expression and sustaining it for at least 42 days. Additionally, this system effectively induces HBsAb production in mice, offering a safe, efficient, and cost-effective platform for both laboratory and clinical gene therapy applications.
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Affiliation(s)
- Huan Zhao
- School of Laboratory Medicine, Key Laboratory of Structure-Specific Small Molecule Drugs, Key Laboratory of Target Discovery and Protein Drug Development in Major Diseases, Chengdu Medical College, Chengdu 610500, China
| | - Yuan-Yuan Zhou
- School of Laboratory Medicine, Key Laboratory of Structure-Specific Small Molecule Drugs, Key Laboratory of Target Discovery and Protein Drug Development in Major Diseases, Chengdu Medical College, Chengdu 610500, China
| | - Shi-Ru Shan
- School of Laboratory Medicine, Key Laboratory of Structure-Specific Small Molecule Drugs, Key Laboratory of Target Discovery and Protein Drug Development in Major Diseases, Chengdu Medical College, Chengdu 610500, China
| | - Zheng-Jie Wu
- School of Laboratory Medicine, Key Laboratory of Structure-Specific Small Molecule Drugs, Key Laboratory of Target Discovery and Protein Drug Development in Major Diseases, Chengdu Medical College, Chengdu 610500, China
| | - Yu Cao
- School of Laboratory Medicine, Key Laboratory of Structure-Specific Small Molecule Drugs, Key Laboratory of Target Discovery and Protein Drug Development in Major Diseases, Chengdu Medical College, Chengdu 610500, China
| | - Guan-Yu Chen
- School of Laboratory Medicine, Key Laboratory of Structure-Specific Small Molecule Drugs, Key Laboratory of Target Discovery and Protein Drug Development in Major Diseases, Chengdu Medical College, Chengdu 610500, China
| | - Yao-Mei Wu
- Yingshan County Hospital of Traditional Chinese Medicine, Nanchong 637700, China
| | - Wen-Kui Sun
- School of Laboratory Medicine, Key Laboratory of Structure-Specific Small Molecule Drugs, Key Laboratory of Target Discovery and Protein Drug Development in Major Diseases, Chengdu Medical College, Chengdu 610500, China
| | - Xun Xia
- The First Affiliated Hospital of Chengdu Medical College, Chengdu 610500, China
| | - Huan Yan
- The First Affiliated Hospital of Traditional Chinese Medicine of Chengdu Medical College , XinDu Hospital of Traditional Chinese Medicine, Chengdu 610500, China.
| | - Ying Xu
- School of Laboratory Medicine, Key Laboratory of Structure-Specific Small Molecule Drugs, Key Laboratory of Target Discovery and Protein Drug Development in Major Diseases, Chengdu Medical College, Chengdu 610500, China; The First Affiliated Hospital of Chengdu Medical College, Chengdu 610500, China.
| | - Jian-Lin Chen
- School of Laboratory Medicine, Key Laboratory of Structure-Specific Small Molecule Drugs, Key Laboratory of Target Discovery and Protein Drug Development in Major Diseases, Chengdu Medical College, Chengdu 610500, China.
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Tenchov R, Hughes KJ, Ganesan M, Iyer KA, Ralhan K, Lotti Diaz LM, Bird RE, Ivanov JM, Zhou QA. Transforming Medicine: Cutting-Edge Applications of Nanoscale Materials in Drug Delivery. ACS NANO 2025; 19:4011-4038. [PMID: 39823199 PMCID: PMC11803921 DOI: 10.1021/acsnano.4c09566] [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: 07/16/2024] [Revised: 12/23/2024] [Accepted: 12/27/2024] [Indexed: 01/19/2025]
Abstract
Since their inception in the early 1960s, the development and use of nanoscale materials have progressed tremendously, and their roles in diverse fields ranging from human health to energy and electronics are undeniable. The application of nanotechnology inventions has revolutionized many aspects of everyday life including various medical applications and specifically drug delivery systems, maximizing the therapeutic efficacy of the contained drugs by means of bioavailability enhancement or minimization of adverse effects. In this review, we utilize the CAS Content Collection, a vast repository of scientific information extracted from journal and patent publications, to analyze trends in nanoscience research relevant to drug delivery in an effort to provide a comprehensive and detailed picture of the use of nanotechnology in this field. We examine the publication landscape in the area to provide insights into current knowledge advances and developments. We review the major classes of nanosized drug delivery systems, their delivery routes, and targeted diseases. We outline the most discussed concepts and assess the advantages of various nanocarriers. The objective of this review is to provide a broad overview of the evolving landscape of current knowledge regarding nanosized drug delivery systems, to outline challenges, and to evaluate growth opportunities. The merit of the review stems from the extensive, wide-ranging coverage of the most up-to-date scientific information, allowing unmatched breadth of landscape analysis and in-depth insights.
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Affiliation(s)
- Rumiana Tenchov
- CAS,
a division of the American Chemical Society, Columbus, Ohio 43210, United States
| | - Kevin J. Hughes
- CAS,
a division of the American Chemical Society, Columbus, Ohio 43210, United States
| | | | - Kavita A. Iyer
- CAS,
a division of the American Chemical Society, Columbus, Ohio 43210, United States
| | | | - Leilani M. Lotti Diaz
- CAS,
a division of the American Chemical Society, Columbus, Ohio 43210, United States
| | - Robert E. Bird
- CAS,
a division of the American Chemical Society, Columbus, Ohio 43210, United States
| | - Julian M. Ivanov
- CAS,
a division of the American Chemical Society, Columbus, Ohio 43210, United States
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Ryu MC, Choi SH. Influence of Polymer Architecture on the Structure of Complex Coacervate Core Micelles: AB + AC versus AB + C Systems. ACS Macro Lett 2025; 14:2-7. [PMID: 39668559 DOI: 10.1021/acsmacrolett.4c00679] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2024]
Abstract
Complex coacervate core micelles (C3Ms), formed through electrostatic interactions between oppositely charged block copolyelectrolytes, are effective delivery vehicles for hydrophilic biomacromolecules. This study investigates the impact of polymer architecture on the C3Ms structure by blending homopolyelectrolytes and diblock copolyelectrolytes as anionic counterparts for cationic diblock copolyelectrolytes. Our results show that the micellar structure, including core size, aggregation number, and corona characteristics, is precisely controlled by the fraction of homopolyelectrolytes. C3Ms formed by the AB + C system have larger core dimensions and aggregation numbers but lower corona brush densities compared to AB + AC systems. These findings highlight that the spatial constraints of polyelectrolytes play a crucial role in determining micellar structure, which can be further understood by balancing the free energies contributed by core block stretching and interfacial tension.
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Affiliation(s)
- Moon-Chul Ryu
- Department of Chemical Engineering, Hongik University, Seoul, 04066, Republic of Korea
| | - Soo-Hyung Choi
- Department of Chemical Engineering, Hongik University, Seoul, 04066, Republic of Korea
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Mathur P, Verma R, Rani L, Kamboj S, Kamboj R, Kamboj T, Bhatt S. Emerging Treatment Options of Pluronic in Designing Colloidal Nano and Micro Carriers for Various Therapies. RECENT PATENTS ON NANOTECHNOLOGY 2025; 19:395-406. [PMID: 38018214 DOI: 10.2174/0118722105255391231018112747] [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: 03/28/2023] [Revised: 08/14/2023] [Accepted: 09/01/2023] [Indexed: 11/30/2023]
Abstract
Poloxamers, commonly known as Pluronics, are a special family of synthetic tri-block copolymers with a core structure made of hydrophobic poly (propylene oxide) chains sandwiched by two hydrophilic poly (ethylene oxide) chains. It is possible to modify the mechanical, bioactive, and microstructural characteristics of Pluronics to simulate the behavior of different types of tissues. Additionally, they are auspicious drug carriers with the capacity to increase therapeutic agent availability and to design nano-drug formulations for various ailments. The nanoformulation composed of Pluronics is more susceptible to cancer cells due to their amphiphilic nature and feature of selfassembling into micelles. Today's expanding poloxamer research is creating new hopes that increase the possibility of new remedies for a brand-new nanomedicine age treatment. This article provides a concise overview of the classification, grading, and attributes of drug delivery systems (DDSs) as well as the potential for Pluronics to create micro and nanocarriers. We subsequently discuss its utility in drug delivery for cancer, gene therapy, anti-infective therapy, antioxidants, anti-diabetic drugs, anti-HIV, Alzheimer's disease, and antimicrobial drugs. This review also highlighted several patented formulations that contain various grades of Pluronics in one or more different ways..The.recent findings in fundamental research in the field properly demonstrate the strong interest in these novel pharmaceutical strategies.
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Affiliation(s)
- Pooja Mathur
- Department of Pharmacy, School of Medical and Allied Sciences, GD Goenka University, Gurugram, 122103, Haryana, India
| | - Ravinder Verma
- Department of Pharmaceutical Sciences, Chaudhary Bansi Lal University, Bhiwani (Haryana), 127021, India
| | - Laxmi Rani
- Department of Pharmacy, School of Medical and Allied Sciences, GD Goenka University, Gurugram, 122103, Haryana, India
| | - Sweta Kamboj
- Guru Gobind Singh College of Pharmacy, Yamuna Nagar, 135001, Haryana, India
| | - Rohit Kamboj
- Guru Gobind Singh College of Pharmacy, Yamuna Nagar, 135001, Haryana, India
| | - Tanu Kamboj
- Guru Gobind Singh College of Pharmacy, Yamuna Nagar, 135001, Haryana, India
| | - Shailendra Bhatt
- Department of Pharmacy, School of Medical and Allied Sciences, GD Goenka University, Gurugram, 122103, Haryana, India
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Di Spirito NA, Grizzuti N, Pasquino R. Self-assembly of Pluronics: A critical review and relevant applications. PHYSICS OF FLUIDS 2024; 36. [DOI: 10.1063/5.0238690] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
Abstract
Pluronics, alias poloxamers, are synthetic amphiphilic copolymers owning a triblock structure with a central hydrophobic poly(propylene oxide) (PPO) segment linked to two lateral hydrophilic poly(ethylene oxide) (PEO) chains. Commercially, Pluronics exist in numerous types according to the length of PPO and PEO chains, exhibiting different behavior and phase diagrams in solution. Concentrated aqueous solutions of Pluronics form thermoreversible gel-like systems. Properties, such as versatility, biocompatibility, nontoxicity, thermosensitivity and self-assembling behavior, make them extremely attractive for numerous applications. This review paper provides an overview on Pluronics, with a focus on their properties and phase behaviors, and on the effect of the presence of salts and additives. Different strategies to endow Pluronics with improved and extra properties, such as their chemical modification and mixed micelles, are briefly illustrated. Furthermore, a synopsis of useful experimental methodologies for understanding the flow properties of Pluronic-based systems is presented, providing a practical guide to their experimental characterization. Eventually, significant advances of Pluronic-based materials are briefly reviewed to elucidate their role in diverse applications, ranging from drug delivery and tissue engineering to bioprinting, cell cultures, personal care industry, conductive hydrogels, and electrocatalytic science. The current article is a critical review of Pluronic block copolymers, not intended as just inert materials but also as systems with functional properties able to revolutionize the paradigm of many technological fields.
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Affiliation(s)
| | - Nino Grizzuti
- DICMaPI, Università degli Studi di Napoli Federico II , P. le Tecchio 80, 80125 Napoli,
| | - Rossana Pasquino
- DICMaPI, Università degli Studi di Napoli Federico II , P. le Tecchio 80, 80125 Napoli,
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Tenchov R, Sasso JM, Zhou QA. Polyglutamine (PolyQ) Diseases: Navigating the Landscape of Neurodegeneration. ACS Chem Neurosci 2024; 15:2665-2694. [PMID: 38996083 PMCID: PMC11311141 DOI: 10.1021/acschemneuro.4c00184] [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: 03/27/2024] [Revised: 06/02/2024] [Accepted: 06/26/2024] [Indexed: 07/14/2024] Open
Abstract
Polyglutamine (polyQ) diseases are a group of inherited neurodegenerative disorders caused by expanded cytosine-adenine-guanine (CAG) repeats encoding proteins with abnormally expanded polyglutamine tract. A total of nine polyQ disorders have been identified, including Huntington's disease, six spinocerebellar ataxias, dentatorubral pallidoluysian atrophy (DRPLA), and spinal and bulbar muscular atrophy (SBMA). The diseases of this class are each considered rare, yet polyQ diseases constitute the largest group of monogenic neurodegenerative disorders. While each subtype of polyQ diseases has its own causative gene, certain pathologic molecular attributes have been implicated in virtually all of the polyQ diseases, including protein aggregation, proteolytic cleavage, neuronal dysfunction, transcription dysregulation, autophagy impairment, and mitochondrial dysfunction. Although animal models of polyQ disease are available helping to understand their pathogenesis and access disease-modifying therapies, there is neither a cure nor prevention for these diseases, with only symptomatic treatments available. In this paper, we analyze data from the CAS Content Collection to summarize the research progress in the class of polyQ diseases. We examine the publication landscape in the area in effort to provide insights into current knowledge advances and developments. We review the most discussed concepts and assess the strategies to combat these diseases. Finally, we inspect clinical applications of products against polyQ diseases with their development pipelines. The objective of this review is to provide a broad overview of the evolving landscape of current knowledge regarding the class of polyQ diseases, to outline challenges, and evaluate growth opportunities to further efforts in combating the diseases.
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Affiliation(s)
- Rumiana Tenchov
- CAS, a division of the American
Chemical Society, Columbus, Ohio 43210, United States
| | - Janet M. Sasso
- CAS, a division of the American
Chemical Society, Columbus, Ohio 43210, United States
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Liu Y, Liang Y, Yuhong J, Xin P, Han JL, Du Y, Yu X, Zhu R, Zhang M, Chen W, Ma Y. Advances in Nanotechnology for Enhancing the Solubility and Bioavailability of Poorly Soluble Drugs. Drug Des Devel Ther 2024; 18:1469-1495. [PMID: 38707615 PMCID: PMC11070169 DOI: 10.2147/dddt.s447496] [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: 11/14/2023] [Accepted: 04/03/2024] [Indexed: 05/07/2024] Open
Abstract
This manuscript offers a comprehensive overview of nanotechnology's impact on the solubility and bioavailability of poorly soluble drugs, with a focus on BCS Class II and IV drugs. We explore various nanoscale drug delivery systems (NDDSs), including lipid-based, polymer-based, nanoemulsions, nanogels, and inorganic carriers. These systems offer improved drug efficacy, targeting, and reduced side effects. Emphasizing the crucial role of nanoparticle size and surface modifications, the review discusses the advancements in NDDSs for enhanced therapeutic outcomes. Challenges such as production cost and safety are acknowledged, yet the potential of NDDSs in transforming drug delivery methods is highlighted. This contribution underscores the importance of nanotechnology in pharmaceutical engineering, suggesting it as a significant advancement for medical applications and patient care.
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Affiliation(s)
- Yifan Liu
- School of Medicine, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, People’s Republic of China
| | - Yushan Liang
- School of Rehabilitation Medicine, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, People’s Republic of China
| | - Jing Yuhong
- School of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, People’s Republic of China
| | - Peng Xin
- School of Medicine, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, People’s Republic of China
| | - Jia Li Han
- School of Health Sciences, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, People’s Republic of China
| | - Yongle Du
- School of Ophthalmology and Optometry, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, People’s Republic of China
| | - Xinru Yu
- School of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, People’s Republic of China
| | - Runhe Zhu
- School of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, People’s Republic of China
| | - Mingxun Zhang
- School of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, People’s Republic of China
| | - Wen Chen
- First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, People’s Republic of China
| | - Yingjie Ma
- First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, People’s Republic of China
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Junnila A, Mortier L, Arbiol A, Harju E, Tomberg T, Hirvonen J, Viitala T, Karttunen AP, Peltonen L. Rheological insights into 3D printing of drug products: Drug nanocrystal-poloxamer gels for semisolid extrusion. Int J Pharm 2024; 655:124070. [PMID: 38554740 DOI: 10.1016/j.ijpharm.2024.124070] [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: 02/06/2024] [Revised: 03/27/2024] [Accepted: 03/27/2024] [Indexed: 04/02/2024]
Abstract
The importance of ink rheology to the outcome of 3D printing is well recognized. However, rheological properties of printing inks containing drug nanocrystals have not been widely investigated. Therefore, the objective of this study was to establish a correlation between the composition of nanocrystal printing ink, the ink rheology, and the entire printing process. Indomethacin was used as a model poorly soluble drug to produce nanosuspensions with improved solubility properties through particle size reduction. The nanosuspensions were further developed into semisolid extrusion 3D printing inks with varying nanocrystal and poloxamer 407 concentrations. Nanocrystals were found to affect the rheological properties of the printing inks both by being less self-supporting and having higher yielding resistances. During printing, nozzle blockages occurred. Nevertheless, all inks were found to be printable. Finally, the rheological properties of the inks were successfully correlated with various printing and product properties. Overall, these experiments shed new light on the rheological properties of printing inks containing nanocrystals.
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Affiliation(s)
- Atte Junnila
- Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, § ,University of Helsinki, Helsinki, Finland.
| | - Laurence Mortier
- Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, § ,University of Helsinki, Helsinki, Finland; Laboratory of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Ghent University, Ghent, Belgium
| | - Alba Arbiol
- Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, § ,University of Helsinki, Helsinki, Finland
| | - Elina Harju
- Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, § ,University of Helsinki, Helsinki, Finland
| | - Teemu Tomberg
- Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, § ,University of Helsinki, Helsinki, Finland
| | - Jouni Hirvonen
- Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, § ,University of Helsinki, Helsinki, Finland
| | - Tapani Viitala
- Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, § ,University of Helsinki, Helsinki, Finland; Pharmaceutical Sciences Laboratory, Faculty of Science and Engineering, Åbo Akademi University, Turku, Finland
| | - Anssi-Pekka Karttunen
- Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, § ,University of Helsinki, Helsinki, Finland
| | - Leena Peltonen
- Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, § ,University of Helsinki, Helsinki, Finland
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Laquintana V, Lopedota AA, Ivone M, Denora N, Franco M, Palazzo G, Gentile L. Celecoxib-hydroxypropyl-β-cyclodextrin inclusion complex in a chitosan/PEO-PPO-PEO block copolymer matrix: Structural effect and drug release. J Colloid Interface Sci 2024; 660:1030-1038. [PMID: 38220494 DOI: 10.1016/j.jcis.2024.01.019] [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: 10/28/2023] [Revised: 12/28/2023] [Accepted: 01/03/2024] [Indexed: 01/16/2024]
Abstract
HYPOTHESIS Triblock copolymers of poly(ethylene oxide) and poly(propylene oxide)-based matrices, such as Poloxamer 407 (P407) or Pluronic® F127, are extensively utilized in drug delivery and permeation systems due to their FDA approval and listing in the US and European Pharmacopoeias. The study hypothesizes that incorporating 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) and the celecoxib-HP-β-CD inclusion complex into a 16 wt% P407 and chitosan blend in an aqueous acetic acid solution will affect the system's rheological and structural properties. EXPERIMENTS Rheological, small-angle X-ray scattering (SAXS), and dynamic light scattering (DLS) experiments were conducted to assess the impact of acetic acid and chitosan on the 16 wt% P407 and chitosan blend. Additionally, in vitro drug release studies were performed to monitor the drug release profile over time. FINDINGS The addition of HP-β-CD was found to inhibit gel formation in the 16 wt% P407 and chitosan blend. However, the presence of the celecoxib-HP-β-CD inclusion complex showed no significant structural effects compared to P407 blended with chitosan alone. Rheological and SAXS analyses demonstrated that acetic acid led to the formation of a lamellar phase due to the lower pH, facilitating injectability. The presence of chitosan in acetic acid resulted in the detection of a hexagonal phase, affecting the release of celecoxib.
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Affiliation(s)
- Valentino Laquintana
- Department of Pharmacy, Pharmaceutical Sciences, University of Bari Aldo Moro, Orabona 4, 70126 Bari, Italy
| | - Angela A Lopedota
- Department of Pharmacy, Pharmaceutical Sciences, University of Bari Aldo Moro, Orabona 4, 70126 Bari, Italy
| | - Marianna Ivone
- Department of Pharmacy, Pharmaceutical Sciences, University of Bari Aldo Moro, Orabona 4, 70126 Bari, Italy
| | - Nunzio Denora
- Department of Pharmacy, Pharmaceutical Sciences, University of Bari Aldo Moro, Orabona 4, 70126 Bari, Italy
| | - Massimo Franco
- Department of Pharmacy, Pharmaceutical Sciences, University of Bari Aldo Moro, Orabona 4, 70126 Bari, Italy
| | - Gerardo Palazzo
- Department of Chemistry, University of Bari Aldo Moro, Orabona 4, Bari 70126, Italy; Center of Colloid and Surface Science (CSGI) Bari Unit, via della Lastruccia 3, Sesto Fiorentino 50019, Italy
| | - Luigi Gentile
- Department of Chemistry, University of Bari Aldo Moro, Orabona 4, Bari 70126, Italy; Center of Colloid and Surface Science (CSGI) Bari Unit, via della Lastruccia 3, Sesto Fiorentino 50019, Italy.
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11
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Menichetti A, Mordini D, Montalti M. Polydopamine Nanosystems in Drug Delivery: Effect of Size, Morphology, and Surface Charge. NANOMATERIALS (BASEL, SWITZERLAND) 2024; 14:303. [PMID: 38334574 PMCID: PMC10856634 DOI: 10.3390/nano14030303] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/01/2024] [Revised: 01/22/2024] [Accepted: 01/23/2024] [Indexed: 02/10/2024]
Abstract
Recently, drug delivery strategies based on nanomaterials have attracted a lot of interest in different kinds of therapies because of their superior properties. Polydopamine (PDA), one of the most interesting materials in nanomedicine because of its versatility and biocompatibility, has been widely investigated in the drug delivery field. It can be easily functionalized to favor processes like cellular uptake and blood circulation, and it can also induce drug release through two kinds of stimuli: NIR light irradiation and pH. In this review, we describe PDA nanomaterials' performance on drug delivery, based on their size, morphology, and surface charge. Indeed, these characteristics strongly influence the main mechanisms involved in a drug delivery system: blood circulation, cellular uptake, drug loading, and drug release. The understanding of the connections between PDA nanosystems' properties and these phenomena is pivotal to obtain a controlled design of new nanocarriers based on the specific drug delivery applications.
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Affiliation(s)
| | | | - Marco Montalti
- Department of Chemistry “Giacomo Ciamician”, University of Bologna, Via Selmi 2, 40126 Bologna, Italy; (A.M.); (D.M.)
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12
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Annamalai A, Karuppaiya V, Ezhumalai D, Cheruparambath P, Balakrishnan K, Venkatesan A. Nano-based techniques: A revolutionary approach to prevent covid-19 and enhancing human awareness. J Drug Deliv Sci Technol 2023; 86:104567. [PMID: 37313114 PMCID: PMC10183109 DOI: 10.1016/j.jddst.2023.104567] [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: 01/25/2023] [Revised: 04/22/2023] [Accepted: 05/13/2023] [Indexed: 06/15/2023]
Abstract
In every century of history, there are many new diseases emerged, which are not even cured by many developed countries. Today, despite of scientific development, new deadly pandemic diseases are caused by microorganisms. Hygiene is considered to be one of the best methods of avoiding such communicable diseases, especially viral diseases. Illness caused by SARS-CoV-2 was termed COVID-19 by the WHO, the acronym derived from "coronavirus disease 2019. The globe is living in the worst epidemic era, with the highest infection and mortality rate owing to COVID-19 reaching 6.89% (data up to March 2023). In recent years, nano biotechnology has become a promising and visible field of nanotechnology. Interestingly, nanotechnology is being used to cure many ailments and it has revolutionized many aspects of our lives. Several COVID-19 diagnostic approaches based on nanomaterial have been developed. The various metal NPs, it is highly anticipated that could be viable and economical alternatives for treating drug resistant in many deadly pandemic diseases in near future. This review focuses on an overview of nanotechnology's increasing involvement in the diagnosis, prevention, and therapy of COVID-19, also this review provides readers with an awareness and knowledge of importance of hygiene.
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Affiliation(s)
- Asaikkutti Annamalai
- Marine Biotechnology Laboratory, Department of Biotechnology, School of Life Sciences, Pondicherry University, Pondicherry, 605 014, Puducherry, India
| | - Vimala Karuppaiya
- Cancer Nanomedicine Laboratory, Department of Zoology, School of Life Sciences, Periyar University, Salem, 636 011, Tamil Nadu, India
| | - Dhineshkumar Ezhumalai
- Dr. Krishnamoorthi Foundation for Advanced Scientific Research, Vellore, 632 001, Tamil Nadu, India
- Manushyaa Blossom Private Limited, Chennai, 600 102, Tamil Nadu, India
| | | | - Kaviarasu Balakrishnan
- Dr. Krishnamoorthi Foundation for Advanced Scientific Research, Vellore, 632 001, Tamil Nadu, India
- Manushyaa Blossom Private Limited, Chennai, 600 102, Tamil Nadu, India
| | - Arul Venkatesan
- Marine Biotechnology Laboratory, Department of Biotechnology, School of Life Sciences, Pondicherry University, Pondicherry, 605 014, Puducherry, India
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Baltin M, Smirnova V, Khamatnurova R, Sabirova D, Samigullin B, Sachenkov O, Baltina T. Functional State of the Motor Centers of the Lumbar Spine after Contusion (Th8-Th9) with Application of Methylprednisolone-Copolymer at the Site of Injury. Biomedicines 2023; 11:2026. [PMID: 37509665 PMCID: PMC10377350 DOI: 10.3390/biomedicines11072026] [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: 05/11/2023] [Revised: 07/06/2023] [Accepted: 07/10/2023] [Indexed: 07/30/2023] Open
Abstract
Spinal cord injuries must be treated as soon as possible. Studies of NASCIS protocols have questioned the use of methylprednisolone therapy. This study aimed to evaluate the effect of local delivery of methylprednisolone succinate in combination with a tri-block copolymer in rats with spinal cord injury. The experiments were conducted in accordance with the bioethical guidelines. We evaluated the state of the motor centers below the level of injury by assessing the amplitude of evoked motor responses in the hind limb muscles of rats during epidural stimulation. Kinematic analysis was performed to examine the stepping cycle in each rat. Trajectories of foot movements were plotted to determine the range of limb motion, maximum foot lift height, and lateral deviation of the foot in rats on the 21st day after spinal cord injury. We have shown that the local application of methylprednisolone succinate in combination with block copolymer leads to recovery of center excitability by 21 days after injury. In rats, they recovered weight-supported locomotion, directional control of walking, and balance. The proposed assessment method provides valuable information on gait disturbances following injury and can be utilized to evaluate the quality of therapeutic interventions.
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Affiliation(s)
- Maxim Baltin
- Research Laboratory "Mechanobiology", Institute of Fundamental Medicine and Biology, Kazan Federal University, 420015 Kazan, Russia
- Research Institute of Sports Reserve Training Technologies, Volga State University of Physical Culture, Sports and Tourism, Universiade Village, 35, 420010 Kazan, Russia
| | - Victoriya Smirnova
- N.I. Lobachevsky Institute of Mathematics and Mechanics, Kazan Federal University, 420008 Kazan, Russia
| | - Regina Khamatnurova
- Interdisciplinary Neuroscience Faculty, Goethe-Universität Frankfurt am Main, 60323 Frankfurt am Main, Germany
| | - Diana Sabirova
- N.I. Lobachevsky Institute of Mathematics and Mechanics, Kazan Federal University, 420008 Kazan, Russia
- Department of Human and Animal Physiology, Institute of Fundamental Medicine and Biology, Kazan Federal University, 76 K. Marx St., 420015 Kazan, Russia
| | - Bulat Samigullin
- Research Laboratory "Mechanobiology", Institute of Fundamental Medicine and Biology, Kazan Federal University, 420015 Kazan, Russia
- NeuroStart Medical Center, 420049 Kazan, Russia
| | - Oskar Sachenkov
- N.I. Lobachevsky Institute of Mathematics and Mechanics, Kazan Federal University, 420008 Kazan, Russia
- Department Machines Science and Engineering Graphics, Tupolev Kazan National Research Technical University, 420111 Kazan, Russia
| | - Tatyana Baltina
- Research Laboratory "Mechanobiology", Institute of Fundamental Medicine and Biology, Kazan Federal University, 420015 Kazan, Russia
- Department of Human and Animal Physiology, Institute of Fundamental Medicine and Biology, Kazan Federal University, 76 K. Marx St., 420015 Kazan, Russia
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Lazarević D, Mušović J, Trtić-Petrović T, Gadžurić S. Partition of parthenolide in ternary {block copolymer + biocompatible ionic liquid or natural deep eutectic solvent + water} systems. Sep Purif Technol 2023. [DOI: 10.1016/j.seppur.2023.123653] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/03/2023]
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15
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Crabtree A, Boehnke N, Bates F, Hackel B. Consequences of poly(ethylene oxide) and poloxamer P188 on transcription in healthy and stressed myoblasts. Proc Natl Acad Sci U S A 2023; 120:e2219885120. [PMID: 37094151 PMCID: PMC10161009 DOI: 10.1073/pnas.2219885120] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2022] [Accepted: 03/26/2023] [Indexed: 04/26/2023] Open
Abstract
Poly(ethylene oxide) (PEO) and poloxamers, a class of poly(ethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide) (PEO-PPO-PEO) triblock copolymers, have many personal and medical care applications, including the stabilization of stressed cellular membranes. Despite the widespread use, the cellular transcriptional response to these molecules is relatively unknown. C2C12 myoblasts, a model muscle cell, were subjected to short-term Poloxamer 188 (P188) and PEO181 (8,000 g/mol) treatment in culture. RNA was extracted and sequenced to quantify transcriptomic impact. The addition of moderate concentrations (14 µM) of either polymer to unstressed cells caused substantial differential gene expression, including at least twofold modulation of 357 and 588 genes, respectively. In addition, evaluation of the transcriptome response to osmotic stress without polymer treatment revealed dramatic change in RNA expression. Interestingly, the addition of polymer to stressed cells-at concentrations that provide physiological protection-did not yield a significant difference in expression of any gene relative to stress alone. Genome-scale expression analysis was corroborated by single-gene quantitative real-time PCR. Changes in protein expression were measured via western blot, which revealed partial alignment with the RNA results. Collectively, the significant changes to expression of multiple genes and resultant protein translation demonstrates an unexpectedly broad biochemical response to these polymers in healthy myoblasts in vitro. Meanwhile, the lack of substantial transcriptional response to polymer treatment in stressed cells highlights the physical nature of that protective mechanism.
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Affiliation(s)
- Adelyn A. Crabtree
- Department of Chemical Engineering and Materials Science, University of Minnesota, Minneapolis, MN55455
| | - Natalie Boehnke
- Department of Chemical Engineering and Materials Science, University of Minnesota, Minneapolis, MN55455
| | - Frank S. Bates
- Department of Chemical Engineering and Materials Science, University of Minnesota, Minneapolis, MN55455
| | - Benjamin J. Hackel
- Department of Chemical Engineering and Materials Science, University of Minnesota, Minneapolis, MN55455
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16
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Ananya A, Holden KG, Gu Z, Nettleton D, Mallapragada SK, Wannemuehler MJ, Kohut ML, Narasimhan B. "Just right" combinations of adjuvants with nanoscale carriers activate aged dendritic cells without overt inflammation. Immun Ageing 2023; 20:10. [PMID: 36895007 PMCID: PMC9996592 DOI: 10.1186/s12979-023-00332-0] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2022] [Accepted: 02/05/2023] [Indexed: 03/11/2023]
Abstract
BACKGROUND The loss in age-related immunological markers, known as immunosenescence, is caused by a combination of factors, one of which is inflammaging. Inflammaging is associated with the continuous basal generation of proinflammatory cytokines. Studies have demonstrated that inflammaging reduces the effectiveness of vaccines. Strategies aimed at modifying baseline inflammation are being developed to improve vaccination responses in older adults. Dendritic cells have attracted attention as an age-specific target because of their significance in immunization as antigen presenting cells that stimulate T lymphocytes. RESULTS In this study, bone marrow derived dendritic cells (BMDCs) were generated from aged mice and used to investigate the effects of combinations of adjuvants, including Toll-like receptor, NOD2, and STING agonists with polyanhydride nanoparticles and pentablock copolymer micelles under in vitro conditions. Cellular stimulation was characterized via expression of costimulatory molecules, T cell-activating cytokines, proinflammatory cytokines, and chemokines. Our results indicate that multiple TLR agonists substantially increase costimulatory molecule expression and cytokines associated with T cell activation and inflammation in culture. In contrast, NOD2 and STING agonists had only a moderate effect on BMDC activation, while nanoparticles and micelles had no effect by themselves. However, when nanoparticles and micelles were combined with a TLR9 agonist, a reduction in the production of proinflammatory cytokines was observed while maintaining increased production of T cell activating cytokines and enhancing cell surface marker expression. Additionally, combining nanoparticles and micelles with a STING agonist resulted in a synergistic impact on the upregulation of costimulatory molecules and an increase in cytokine secretion from BMDCs linked with T cell activation without excessive secretion of proinflammatory cytokines. CONCLUSIONS These studies provide new insights into rational adjuvant selection for vaccines for older adults. Combining appropriate adjuvants with nanoparticles and micelles may lead to balanced immune activation characterized by low inflammation, setting the stage for designing next generation vaccines that can induce mucosal immunity in older adults.
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Affiliation(s)
- Ananya Ananya
- Nanovaccine Institute, Iowa State University, Ames, IA, 50011, USA
- Department of Chemical and Biological Engineering, Iowa State University, Ames, IA, 50011, USA
| | - Kaitlyn G Holden
- Nanovaccine Institute, Iowa State University, Ames, IA, 50011, USA
| | - Zhiling Gu
- Department of Statistics, Iowa State University, Ames, IA, 50011, USA
| | - Dan Nettleton
- Department of Statistics, Iowa State University, Ames, IA, 50011, USA
| | - Surya K Mallapragada
- Nanovaccine Institute, Iowa State University, Ames, IA, 50011, USA
- Department of Chemical and Biological Engineering, Iowa State University, Ames, IA, 50011, USA
| | | | - Marian L Kohut
- Nanovaccine Institute, Iowa State University, Ames, IA, 50011, USA
- Department of Kinesiology, Iowa State University, Ames, IA, 50011, USA
| | - Balaji Narasimhan
- Nanovaccine Institute, Iowa State University, Ames, IA, 50011, USA.
- Department of Chemical and Biological Engineering, Iowa State University, Ames, IA, 50011, USA.
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17
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Recombinant endonuclease III protein from Leishmania infantum associated with Th1-type adjuvants is immunogenic and induces protection against visceral leishmaniasis. Mol Immunol 2023; 155:79-90. [PMID: 36731193 DOI: 10.1016/j.molimm.2023.01.011] [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: 07/18/2022] [Revised: 12/12/2022] [Accepted: 01/24/2023] [Indexed: 02/04/2023]
Abstract
Vaccination against visceral leishmaniasis (VL) should be considered as a safe and effective measure to disease control; however, few vaccines are available against canine VL and there is no an approved human vaccine. In this context, in the present study, we evaluated the endonuclease III (ENDO) protein, which was recently showed to be antigenic for human disease, as a vaccine candidate against Leishmania infantum infection. The recombinant protein (rENDO) was administered in BALB/c mice alone or associated with saponin (rENDO/Sap) or micelles (rENDO/Mic) as adjuvants. Controls received saline, saponin or empty micelles. Results showed that both rENDO/Sap and rENDO/Mic compositions induced higher levels of IFN-γ, IL-12, TNF-α, and GM-CSF cytokines, besides nitrite and IgG2a isotype antibodies, before and after challenge infection, which were related to both CD4+ and CD8+ T cell subtypes. The immunological results contributed to significant reductions in the parasite load found in the spleens, livers, bone marrows and draining lymph nodes of the vaccinated animals. In general, mice immunized with rENDO/Mic presented a slightly higher Th1-type cellular and humoral immune response, as compared to those receiving rENDO/Sap. In addition, saponin caused a slight to moderate inflammatory edema in their vaccinated footpads, which was not observed when micelles were used with rENDO. In addition, a preliminary analysis showed that the recombinant protein was immunogenic to human cells cultures, since PBMCs from treated VL patients and healthy subjects showed higher lymphoproliferation and IFN-γ production in the culture supernatants. In conclusion, data suggest that rENDO could be considered as a candidate to be evaluated in future studies as vaccine to protect against VL.
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18
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Shershakova NN, Andreev SM, Tomchuk AA, Makarova EA, Nikonova AA, Turetskiy EA, Petukhova OA, Kamyshnikov OY, Ivankov OI, Kyzyma OA, Tomchuk OV, Avdeev MV, Dvornikov AS, Kudlay DA, Khaitov MR. Wound healing activity of aqueous dispersion of fullerene C 60 produced by "green technology". NANOMEDICINE : NANOTECHNOLOGY, BIOLOGY, AND MEDICINE 2023; 47:102619. [PMID: 36272619 DOI: 10.1016/j.nano.2022.102619] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/21/2022] [Revised: 08/13/2022] [Accepted: 10/11/2022] [Indexed: 11/06/2022]
Abstract
In addition to exhibited antioxidant and anti-inflammatory activity, fullerene C60 is a promising wound healing agent. An important stage in the production of fullerene-based ointments is the stability of the aqueous fullerene dispersion (AFD) with minimum size of colloidal fullerene aggregates and sufficiently high concentration. To achieve these parameters tangential flow filtration of fullerene C60 was used ("green technology"). As estimated by small-angle neutron scattering and dynamic light scattering purified AFDs with narrow-size distribution nanoclusters have a size of 6 nm and are assembled into agglomerates which reach a size of 150 nm. The ability of the AFD to exhibit regenerative activity was studied using the animal wound model. This study shows for the first time that the fullerene-based composition stimulates the healing of wounds of various origins. We assume that the mechanism of the AFD wound-healing activity is associated with the aryl hydrocarbon receptor and macrophages activity.
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Affiliation(s)
- N N Shershakova
- NRC Institute of Immunology FMBA of Russia, Kashirskoe shosse, 24, Moscow 115522, Russian Federation.
| | - S M Andreev
- NRC Institute of Immunology FMBA of Russia, Kashirskoe shosse, 24, Moscow 115522, Russian Federation
| | - A A Tomchuk
- International intergovernmental organization Joint Institute for Nuclear Research, st. Joliot-Curie, 6, Dubna, Moscow Region 141980, Russian Federation
| | - E A Makarova
- NRC Institute of Immunology FMBA of Russia, Kashirskoe shosse, 24, Moscow 115522, Russian Federation
| | - A A Nikonova
- NRC Institute of Immunology FMBA of Russia, Kashirskoe shosse, 24, Moscow 115522, Russian Federation
| | - E A Turetskiy
- NRC Institute of Immunology FMBA of Russia, Kashirskoe shosse, 24, Moscow 115522, Russian Federation
| | - O A Petukhova
- NRC Institute of Immunology FMBA of Russia, Kashirskoe shosse, 24, Moscow 115522, Russian Federation
| | - O Y Kamyshnikov
- NRC Institute of Immunology FMBA of Russia, Kashirskoe shosse, 24, Moscow 115522, Russian Federation
| | - O I Ivankov
- International intergovernmental organization Joint Institute for Nuclear Research, st. Joliot-Curie, 6, Dubna, Moscow Region 141980, Russian Federation; Moscow Institute of Physics and Technology, 9 Institutskiy per., Dolgoprudny, Moscow Region 141701, Russian Federation
| | - O A Kyzyma
- Taras Shevchenko National University of Kyiv, 64/13, Volodymyrska Street, Kyiv 0160, Ukraine
| | - O V Tomchuk
- International intergovernmental organization Joint Institute for Nuclear Research, st. Joliot-Curie, 6, Dubna, Moscow Region 141980, Russian Federation; Taras Shevchenko National University of Kyiv, 64/13, Volodymyrska Street, Kyiv 0160, Ukraine
| | - M V Avdeev
- International intergovernmental organization Joint Institute for Nuclear Research, st. Joliot-Curie, 6, Dubna, Moscow Region 141980, Russian Federation
| | - A S Dvornikov
- Pirogov Russian National Research Medical University, 1 Ostrovityanov St., Moscow 119997, Russian Federation
| | - D A Kudlay
- NRC Institute of Immunology FMBA of Russia, Kashirskoe shosse, 24, Moscow 115522, Russian Federation; I.M. Sechenov First Moscow State Medical University (Sechenov University), 8-2 Trubetskaya str., Moscow 119991, Russian Federation
| | - M R Khaitov
- NRC Institute of Immunology FMBA of Russia, Kashirskoe shosse, 24, Moscow 115522, Russian Federation; Pirogov Russian National Research Medical University, 1 Ostrovityanov St., Moscow 119997, Russian Federation
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19
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Cui Z, Jiao Y, Pu L, Tang JZ, Wang G. The Progress of Non-Viral Materials and Methods for Gene Delivery to Skeletal Muscle. Pharmaceutics 2022; 14:2428. [PMID: 36365246 PMCID: PMC9695315 DOI: 10.3390/pharmaceutics14112428] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2022] [Revised: 10/27/2022] [Accepted: 11/02/2022] [Indexed: 09/10/2024] Open
Abstract
Since Jon A. Wolff found skeletal muscle cells being able to express foreign genes and Russell J. Mumper increased the gene transfection efficiency into the myocytes by adding polymers, skeletal muscles have become a potential gene delivery and expression target. Different methods have been developing to deliver transgene into skeletal muscles. Among them, viral vectors may achieve potent gene delivery efficiency. However, the potential for triggering biosafety risks limited their clinical applications. Therefore, non-viral biomaterial-mediated methods with reliable biocompatibility are promising tools for intramuscular gene delivery in situ. In recent years, a series of advanced non-viral gene delivery materials and related methods have been reported, such as polymers, liposomes, cell penetrating peptides, as well as physical delivery methods. In this review, we summarized the research progresses and challenges in non-viral intramuscular gene delivery materials and related methods, focusing on the achievements and future directions of polymers.
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Affiliation(s)
- Zhanpeng Cui
- National Engineering Research Center for Biomaterials, College of Biomedical Engineering, Sichuan University, Chengdu 610064, China
| | - Yang Jiao
- National Engineering Research Center for Biomaterials, College of Biomedical Engineering, Sichuan University, Chengdu 610064, China
| | - Linyu Pu
- School of Materials and Chemistry, Southwest University of Science and Technology, Mianyang 621010, China
| | - James Zhenggui Tang
- Research Institute in Healthcare Science, Faculty of Science & Engineering, University of Wolverhampton, Wolverhampton WV1 1SB, UK
| | - Gang Wang
- National Engineering Research Center for Biomaterials, College of Biomedical Engineering, Sichuan University, Chengdu 610064, China
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20
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Souza RLD, Dantas AGB, Melo CDO, Felício IM, Oliveira EE. Nanotechnology as a tool to improve the biological activity of carvacrol: A review. J Drug Deliv Sci Technol 2022. [DOI: 10.1016/j.jddst.2022.103834] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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21
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Rajan R, Pal K, Jayadev D, Jayan JS, U A, Appukuttan S, de Souza FG, Joseph K, Kumar SS. Polymeric Nanoparticles in Hybrid Catalytic Processing and Drug Delivery System. Top Catal 2022. [DOI: 10.1007/s11244-022-01697-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
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22
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Renal cell carcinoma management: A step to nano-chemoprevention. Life Sci 2022; 308:120922. [PMID: 36058262 DOI: 10.1016/j.lfs.2022.120922] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2022] [Revised: 08/12/2022] [Accepted: 08/26/2022] [Indexed: 11/21/2022]
Abstract
Renal cell carcinoma (RCC) is one of the most common kidney cancers, responsible for nearly 90 % of all renal malignancies. Despite the availability of many treatment strategies, RCC still remains to be an incurable disease due to its resistivity towards conventional therapies. Nanotechnology is an emerging field of science that offers newer possibilities in therapeutics including cancer medicine, specifically by targeted delivery of anticancer drugs. Several phytochemicals are known for their anti-cancer properties and have been regarded as chemopreventive agents. However, the hydrophobic nature of many phytochemicals decreases its bioavailability and distribution, thus showing limited therapeutic effect. Application of nanotechnology to enhance chemoprevention is an effective strategy to increase the bioavailability of phytochemicals and thereby its therapeutic efficacy. The present review focuses on the utility of nanotechnology in RCC treatment and chemopreventive agents of RCC. We have also visualized the future prospects of nanomolecules in the prevention and cure of RCC.
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23
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Arafa KK, Hamzawy MA, Mousa SA, El-Sherbiny IM. Mitochondria-targeted alginate/triphenylphosphonium-grafted-chitosan for treatment of hepatocellular carcinoma. RSC Adv 2022; 12:21690-21703. [PMID: 35975035 PMCID: PMC9350814 DOI: 10.1039/d2ra03240f] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2022] [Accepted: 07/18/2022] [Indexed: 11/21/2022] Open
Abstract
Mitochondrial targeting of anticancer drugs can effectively eradicate chemotherapy-refractory cells through different mechanisms. This work presents the rational designing of mitochondria-targeted core–shell polymeric nanoparticles (NPs) for efficient delivery of doxorubicin (DOX) to the hepatic carcinoma mitochondria. DOX was electrostatically nano-complexed with sodium alginate (SAL) then coated with mitotropic triphenylphosphonium-grafted chitosan (TPP+-g-CS) nanoshell. Polyvinyl alcohol (PVA) was co-solubilized into the TPP+-g-CS solution to enhance the stability of the developed NPs. The optimum NPs formula is composed of TPP+-g-CS (0.05% w/v) coating a DOX-SAL core complex (0.05% w/v), with 0.2% PVA relative to CS (w/w). The optimum NPs attained an entrapment efficiency of 63.33 ± 10.18%; exhibited a spherical shape with particle size of 70–110 nm and a positive surface charge which enhances mitochondrial uptake. FTIR and DSC studies results were indicative of an efficacious poly-complexation. In vitro biological experiments proved that the developed mitotropic NPs exhibited a significantly lower IC50, effectively induced apoptotic cell death and cell cycle arrest. Moreover, the in vivo studies demonstrated an enhanced antitumor bioactivity for the mitotropic NPs along with a reduced biological toxicity profile. In conclusion, this study proposes a promising nanocarrier system for the efficient targeting of DOX to the mitochondria of hepatic tumors. Mitochondrial targeting of anticancer drugs can effectively eradicate tumour cells. TPP+-grafted-chitosan based core–shell nanoparticles were successfully internalized into the mitochondria of HCC cells. Also exhibited antiproliferative activity against liver cancer.![]()
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Affiliation(s)
- Kholoud K Arafa
- Nanomedicine Research Labs, Center for Materials Science (CMS), Zewail City of Science and Technology Ahmed Zewail Road, October Gardens, 6th of October City 12578 Giza Egypt
| | - Mohamed A Hamzawy
- Pharmacology & Toxicology Department, Faculty of Pharmacy, Fayoum University Fayoum Egypt
| | - Shaker A Mousa
- Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences Rensselaer NY 12144 USA
| | - Ibrahim M El-Sherbiny
- Nanomedicine Research Labs, Center for Materials Science (CMS), Zewail City of Science and Technology Ahmed Zewail Road, October Gardens, 6th of October City 12578 Giza Egypt
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24
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Jain A, Kishore N. Micellar properties of pluronics in combination with cationic surfactant and interaction with lysozyme: Thermodynamic evaluation. J Mol Liq 2022. [DOI: 10.1016/j.molliq.2022.119303] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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25
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Trivedi V, Ajiboye AL, Coleman NJ, Bhomia R, Bascougnano M. Melting Point Depression of Poly(ethylene oxide)-Poly(propylene oxide)-Poly(ethylene oxide) Triblock Polymers in Supercritical Carbon Dioxide in the Presence of Menthol as a Solid Co-Plasticiser. Polymers (Basel) 2022; 14:2825. [PMID: 35890600 PMCID: PMC9318245 DOI: 10.3390/polym14142825] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2022] [Revised: 07/06/2022] [Accepted: 07/07/2022] [Indexed: 11/16/2022] Open
Abstract
The melting behaviour of the triblock polymers, Pluronic F38, F68, F77, F108, and F127, was investigated in pressurised CO2 and in the presence of menthol. The melting points of the polymers combined with 0, 10, 25, and 50 wt% of menthol were studied at atmospheric pressure and compared with those at 10 and 20 MPa in supercritical carbon dioxide (scCO2). The highest melting point depressions of 16.8 ± 0.5 °C and 29.0 ± 0.3 °C were observed at 10 and 20 MPa, respectively. The melting point of triblock polymers in pressurised CO2 was found to be dependent on molecular weight, poly(propylene oxide) (PPO) content, and menthol percentage. The melting point of most of the polymers studied in this work can be reduced to room temperature, which can be pivotal to the formulation development of thermolabile substances using these polymers.
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Affiliation(s)
- Vivek Trivedi
- Medway School of Pharmacy, University of Kent, Central Avenue, Chatham Maritime, Kent ME4 4TB, UK;
| | - Adejumoke Lara Ajiboye
- Medway School of Pharmacy, University of Kent, Central Avenue, Chatham Maritime, Kent ME4 4TB, UK;
| | - Nichola J. Coleman
- Department of Pharmaceutical, Chemical and Environmental Science, University of Greenwich, Central Avenue, Chatham Maritime, Kent ME4 4TB, UK; (N.J.C.); (M.B.)
| | - Ruchir Bhomia
- Procter & Gamble, 452 Basingstoke Road, Reading RG2 0RX, UK;
| | - Marion Bascougnano
- Department of Pharmaceutical, Chemical and Environmental Science, University of Greenwich, Central Avenue, Chatham Maritime, Kent ME4 4TB, UK; (N.J.C.); (M.B.)
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Jaquilin P J R, Oluwafemi OS, Thomas S, Oyedeji AO. Recent advances in drug delivery nanocarriers incorporated in temperature-sensitive Pluronic F-127–A critical review. J Drug Deliv Sci Technol 2022. [DOI: 10.1016/j.jddst.2022.103390] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
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Kumari S, Goyal A, Sönmez Gürer E, Algın Yapar E, Garg M, Sood M, Sindhu RK. Bioactive Loaded Novel Nano-Formulations for Targeted Drug Delivery and Their Therapeutic Potential. Pharmaceutics 2022; 14:pharmaceutics14051091. [PMID: 35631677 PMCID: PMC9146286 DOI: 10.3390/pharmaceutics14051091] [Citation(s) in RCA: 38] [Impact Index Per Article: 12.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2022] [Revised: 05/14/2022] [Accepted: 05/16/2022] [Indexed: 12/13/2022] Open
Abstract
Plant-based medicines have received a lot of attention in recent years. Such medicines have been employed to treat medical conditions since ancient times, and in those times only the observed symptoms were used to determine dose accuracy, dose efficacy, and therapy. Rather than novel formulations, the current research work on plant-based medicines has mostly concentrated on medicinal active phytoconstituents. In the past recent decades, however, researchers have made significant progress in developing "new drug delivery systems" (NDDS) to enhance therapeutic efficacy and reduce unwanted effects of bioactive compounds. Nanocapsules, polymer micelles, liposomes, nanogels, phytosomes, nano-emulsions, transferosomes, microspheres, ethosomes, injectable hydrogels, polymeric nanoparticles, dendrimers, and other innovative therapeutic formulations have all been created using bioactive compounds and plant extracts. The novel formulations can improve solubility, therapeutic efficacy, bioavailability, stability, tissue distribution, protection from physical and chemical damage, and prolonged and targeted administration, to name a few. The current study summarizes existing research and the development of new formulations, with a focus on herbal bioactive components.
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Affiliation(s)
- Sapna Kumari
- Chitkara College of Pharmacy, Chitkara University, Rajpura 140401, Punjab, India; (S.K.); (A.G.); (M.G.)
| | - Anju Goyal
- Chitkara College of Pharmacy, Chitkara University, Rajpura 140401, Punjab, India; (S.K.); (A.G.); (M.G.)
| | - Eda Sönmez Gürer
- Faculty of Pharmacy, Sivas Cumhuriyet University, 58140 Sivas, Turkey; (E.S.G.); (E.A.Y.)
| | - Evren Algın Yapar
- Faculty of Pharmacy, Sivas Cumhuriyet University, 58140 Sivas, Turkey; (E.S.G.); (E.A.Y.)
| | - Madhukar Garg
- Chitkara College of Pharmacy, Chitkara University, Rajpura 140401, Punjab, India; (S.K.); (A.G.); (M.G.)
| | - Meenakshi Sood
- Chitkara School of Health Sciences, Chitkara University, Rajpura 140401, Punjab, India;
| | - Rakesh K. Sindhu
- Chitkara College of Pharmacy, Chitkara University, Rajpura 140401, Punjab, India; (S.K.); (A.G.); (M.G.)
- Correspondence:
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Poloxamer 188 as surfactant in biological formulations - An alternative for polysorbate 20/80? Int J Pharm 2022; 620:121706. [PMID: 35367584 DOI: 10.1016/j.ijpharm.2022.121706] [Citation(s) in RCA: 62] [Impact Index Per Article: 20.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2021] [Revised: 03/05/2022] [Accepted: 03/26/2022] [Indexed: 01/25/2023]
Abstract
Surfactants are used to stabilize biologics. Particularly, polysorbates (Tween® 20 and Tween® 80) dominate the group of surfactants in protein and especially antibody drug products. Since decades drug developers rely on the ethoxylated sorbitan fatty acid ester mixtures to stabilize sensitive molecules such as proteins. Reasons are (i) excellent stabilizing properties, and (ii) well recognized safety and tolerability profile of these polysorbates in humans, especially for parenteral applications. However, over the past decade concerns regarding the stability of these two polysorbates were raised. The search of alternatives with preferably less reservations concerning degradation and product quality reducing issues leads, among others, to poloxamer 188 (e.g. Kolliphor® P188), a nonionic triblock-copolymer surfactant. This review sums up our current knowledge related to the characterization and physico-chemical properties of poloxamer 188, its analytics and stability properties for biological formulations. Furthermore, the advantages and disadvantages as a suitable polysorbate-alternative for the stabilization of biologics are discussed.
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Vitorino LS, dos Santos TC, Bessa IA, Santos EC, Verçoza BR, de Oliveira LAS, Rodrigues JC, Ronconi CM. Fabrication data of two light-responsive systems to release an antileishmanial drug activated by infrared photothermal heating. Data Brief 2022; 41:107841. [PMID: 35146082 PMCID: PMC8802065 DOI: 10.1016/j.dib.2022.107841] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2022] [Revised: 01/10/2022] [Accepted: 01/14/2022] [Indexed: 12/02/2022] Open
Abstract
The data provided in this study are related to the fabrication of two light-responsive systems based on reduced graphene oxide (rGO) functionalized with the polymers Pluronic P123 (P123), rGO-P123, and polyethyleneimine (PEI), rGO-PEI, and loaded with amphotericin B (AmB), an antileishmanial drug. Here are described the experimental design to obtain the systems and characterization methods, such as Attenuated Total Reflectance-Fourier Transform Infrared Spectroscopy (ATR-FTIR), Raman Spectroscopy, Powder X-Ray Diffraction, Transmission Electron Microscopy, Scanning Electron Microscopy and Thermogravimetric Analyses. Also, AmB spectroscopy studies are described. The materials rGO-P123 and rGO-PEI were loaded with AmB and the optimization of AmB and polymer fragments structures revealed several possible hydrogen bonds formed between the materials and the drug. The drug release was analyzed with and without Near-Infrared (NIR) light. In the studies conducted under NIR light irradiation for 10 min, an infrared lamp was disposed at 64 cm from the samples and an optical fiber thermometer was employed to measure the temperature variation. Cytotoxicity studies and antiproliferative assays against Leishmania amazonensis promastigotes were evaluated. The complete work data entitled Amphotericin-B-Loaded Polymer-Functionalized Reduced Graphene Oxides for Leishmania amazonensis Chemo-Photothermal Therapy have been published to Colloids and Surfaces B: Bionterfaces (https://doi.org/10.1016/j.colsurfb.2021.112169) [1].
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Affiliation(s)
- Letícia S. Vitorino
- Departamento de Química Inorgânica, Universidade Federal Fluminense, Campus do Valonguinho, Niterói-RJ, 24020-150, Brazil
| | - Thiago C. dos Santos
- Departamento de Química Inorgânica, Universidade Federal Fluminense, Campus do Valonguinho, Niterói-RJ, 24020-150, Brazil
| | - Isabela A.A. Bessa
- Departamento de Química Inorgânica, Universidade Federal Fluminense, Campus do Valonguinho, Niterói-RJ, 24020-150, Brazil
| | - Evelyn C.S. Santos
- Departamento de Química Inorgânica, Universidade Federal Fluminense, Campus do Valonguinho, Niterói-RJ, 24020-150, Brazil
- Present address: Centro Brasileiro de Pesquisas Físicas, Urca-RJ, 22290-180, Brazil
| | - Brunno R.F. Verçoza
- Núcleo Multidisciplinar de Pesquisa em Biologia (NUMPEX-Bio), Campus UFRJ-Duque de Caxias Prof. Geraldo Cidade, Universidade Federal do Rio de Janeiro, Duque de Caxias, RJ, Brazil
| | - Luiz Augusto S. de Oliveira
- Núcleo Multidisciplinar de Pesquisa em Nanotecnologia (NUMPEX-Nano), Campus UFRJ-Duque de Caxias Prof. Geraldo Cidade, Universidade Federal do Rio de Janeiro, Duque de Caxias, RJ, Brazil
| | - Juliany C.F. Rodrigues
- Núcleo Multidisciplinar de Pesquisa em Biologia (NUMPEX-Bio), Campus UFRJ-Duque de Caxias Prof. Geraldo Cidade, Universidade Federal do Rio de Janeiro, Duque de Caxias, RJ, Brazil
| | - Célia M. Ronconi
- Departamento de Química Inorgânica, Universidade Federal Fluminense, Campus do Valonguinho, Niterói-RJ, 24020-150, Brazil
- Corresponding author. @RonconiCelia
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Batista CM, de Queiroz LA, Alves ÂV, Reis EC, Santos FA, Castro TN, Lima BS, Araújo AN, Godoy CA, Severino P, Cano A, Santini A, Capasso R, de Albuquerque Júnior RL, Cardoso JC, Souto EB. Photoprotection and skin irritation effect of hydrogels containing hydroalcoholic extract of red propolis: A natural pathway against skin cancer. Heliyon 2022; 8:e08893. [PMID: 35198766 PMCID: PMC8842011 DOI: 10.1016/j.heliyon.2022.e08893] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2021] [Revised: 09/30/2021] [Accepted: 01/29/2022] [Indexed: 12/13/2022] Open
Abstract
The use of natural products in sunscreen formulations as a prophylactic measure against skin cancer is receiving special attention attributed to the photoprotective and antioxidant properties of their chemical components. In this work, we describe the development of topical hydrogel formulations containing hydroalcoholic extract of red propolis (HERP), and the evaluation of the dermal sensitizing effect of the developed products. Sunscreen formulations composed of HERP in different concentrations (1.5, 2.5 or 3.5% w/w) alone or in combination with a chemical (octyl methoxycinnamate) and/or physical (titanium dioxide) filters were developed using poloxamer 407 as gel basis. The preliminary and accelerated stability tests, texture analysis and spreadability tests were performed. All formulations revealed to be stable in preliminary stability assessment. The formulations containing HERP 1.5 and 2.5% alone or associated with the filters showed intense modifications during accelerated stability test, which were confirmed by rheological analyses. The incorporation of HERP and filters in the poloxamer hydrogel decreased the toughness of product (p < 0.05) and the formulation containing HERP alone presented the lowest adhesivity (p < 0.001). The incorporation of HERP in the hydrogel decreased the poloxamer transition temperature, showing different rheological behavior with the increase of HERP concentration. The developed formulations were stable, exhibited non-Newtonian and pseudoplastic behavior, showing in vivo skin compatibility and no skin irritancy.
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Affiliation(s)
- Cinthia M. Batista
- Biotechnological Postgraduate Program, University of Tiradentes (Unit), Av. Murilo Dantas 300, 49010-390, Aracaju, Brazil
| | - Luma A. de Queiroz
- Biotechnological Postgraduate Program, University of Tiradentes (Unit), Av. Murilo Dantas 300, 49010-390, Aracaju, Brazil
| | - Ângela V.F. Alves
- Biotechnological Postgraduate Program, University of Tiradentes (Unit), Av. Murilo Dantas 300, 49010-390, Aracaju, Brazil
| | - Elisiane C.A. Reis
- Institute of Technology and Research (ITP), University of Tiradentes (Unit), Av. Murilo Dantas 300, 49010-390, Aracaju, Brazil
| | - Fagne A. Santos
- Biotechnological Postgraduate Program, University of Tiradentes (Unit), Av. Murilo Dantas 300, 49010-390, Aracaju, Brazil
| | - Tailaine N. Castro
- Biotechnological Postgraduate Program, University of Tiradentes (Unit), Av. Murilo Dantas 300, 49010-390, Aracaju, Brazil
| | - Bruno S. Lima
- Department of Pharmacy, Federal University of Sergipe, Aracaju, Sergipe, Brazil
| | - Adriano N.S. Araújo
- Department of Pharmacy, Federal University of Sergipe, Aracaju, Sergipe, Brazil
| | - Charles A.P. Godoy
- Biotechnological Postgraduate Program, University of Tiradentes (Unit), Av. Murilo Dantas 300, 49010-390, Aracaju, Brazil
| | - Patricia Severino
- Biotechnological Postgraduate Program, University of Tiradentes (Unit), Av. Murilo Dantas 300, 49010-390, Aracaju, Brazil
- Institute of Technology and Research (ITP), University of Tiradentes (Unit), Av. Murilo Dantas 300, 49010-390, Aracaju, Brazil
| | - Amanda Cano
- Department of Pharmacy, Pharmaceutical Technology and Physical Chemistry, Faculty of Pharmacy, University of Barcelona, 08028, Barcelona, Spain
- Institute of Nanoscience and Nanotechnology, Universitat de Barcelona, 08028, Barcelona, Spain
| | - Antonello Santini
- Department of Pharmacy, University of Napoli Federico II, 80131, Napoli, Italy
| | - Raffaele Capasso
- Department of Agricultural Sciences, University of Naples Federico II, 80055, Portici, Naples, Italy
| | - Ricardo L.C. de Albuquerque Júnior
- Biotechnological Postgraduate Program, University of Tiradentes (Unit), Av. Murilo Dantas 300, 49010-390, Aracaju, Brazil
- Institute of Technology and Research (ITP), University of Tiradentes (Unit), Av. Murilo Dantas 300, 49010-390, Aracaju, Brazil
| | - Juliana C. Cardoso
- Biotechnological Postgraduate Program, University of Tiradentes (Unit), Av. Murilo Dantas 300, 49010-390, Aracaju, Brazil
- Institute of Technology and Research (ITP), University of Tiradentes (Unit), Av. Murilo Dantas 300, 49010-390, Aracaju, Brazil
- Corresponding author.
| | - Eliana B. Souto
- Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal
- CEB—Centre of Biological Engineering, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal
- LABBELS—Associate Laboratory, Braga, Guimarães, Portugal
- Corresponding author.
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Al Sharabati M, Sabouni R, Husseini GA. Biomedical Applications of Metal-Organic Frameworks for Disease Diagnosis and Drug Delivery: A Review. NANOMATERIALS (BASEL, SWITZERLAND) 2022; 12:277. [PMID: 35055294 PMCID: PMC8780624 DOI: 10.3390/nano12020277] [Citation(s) in RCA: 63] [Impact Index Per Article: 21.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/12/2021] [Revised: 01/07/2022] [Accepted: 01/11/2022] [Indexed: 12/19/2022]
Abstract
Metal-organic frameworks (MOFs) are a novel class of porous hybrid organic-inorganic materials that have attracted increasing attention over the past decade. MOFs can be used in chemical engineering, materials science, and chemistry applications. Recently, these structures have been thoroughly studied as promising platforms for biomedical applications. Due to their unique physical and chemical properties, they are regarded as promising candidates for disease diagnosis and drug delivery. Their well-defined structure, high porosity, tunable frameworks, wide range of pore shapes, ultrahigh surface area, relatively low toxicity, and easy chemical functionalization have made them the focus of extensive research. This review highlights the up-to-date progress of MOFs as potential platforms for disease diagnosis and drug delivery for a wide range of diseases such as cancer, diabetes, neurological disorders, and ocular diseases. A brief description of the synthesis methods of MOFs is first presented. Various examples of MOF-based sensors and DDSs are introduced for the different diseases. Finally, the challenges and perspectives are discussed to provide context for the future development of MOFs as efficient platforms for disease diagnosis and drug delivery systems.
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Affiliation(s)
- Miral Al Sharabati
- Department of Chemical Engineering, American University of Sharjah, Sharjah P.O. Box 26666, United Arab Emirates;
- The Material Science and Engineering Program, College of Arts and Sciences, American University of Sharjah, Sharjah P.O. BOX 26666, United Arab Emirates
| | - Rana Sabouni
- Department of Chemical Engineering, American University of Sharjah, Sharjah P.O. Box 26666, United Arab Emirates;
- The Material Science and Engineering Program, College of Arts and Sciences, American University of Sharjah, Sharjah P.O. BOX 26666, United Arab Emirates
| | - Ghaleb A. Husseini
- Department of Chemical Engineering, American University of Sharjah, Sharjah P.O. Box 26666, United Arab Emirates;
- The Material Science and Engineering Program, College of Arts and Sciences, American University of Sharjah, Sharjah P.O. BOX 26666, United Arab Emirates
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Arredondo-Ochoa T, Silva-Martínez GA. Microemulsion Based Nanostructures for Drug Delivery. FRONTIERS IN NANOTECHNOLOGY 2022. [DOI: 10.3389/fnano.2021.753947] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Most of the active pharmaceutical compounds are often prone to display low bioavailability and biological degradation represents an important drawback. Due to the above, the development of a drug delivery system (DDS) that enables the introduction of a pharmaceutical compound through the body to achieve a therapeutic effect in a controlled manner is an expanding application. Henceforth, new strategies have been developed to control several parameters considered essential for enhancing delivery of drugs. Nanostructure synthesis by microemulsions (ME) consist of enclosing a substance within a wall material at the nanoscale level, allowing to control the size and surface area of the resulting particle. This nanotechnology has shown the importance on targeted drug delivery to improve their stability by protecting a bioactive compound from an adverse environment, enhanced bioavailability as well as controlled release. Thus, a lower dose administration could be achieved by minimizing systemic side effects and decreasing toxicity. This review will focus on describing the different biocompatible nanostructures synthesized by ME as controlled DDS for therapeutic purposes.
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DPD Study on the Interfacial Properties of PEO/PEO-PPO-PEO/PPO Ternary Blends: Effects of Pluronic Structure and Concentration. Polymers (Basel) 2021; 13:polym13172866. [PMID: 34502907 PMCID: PMC8433662 DOI: 10.3390/polym13172866] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2021] [Revised: 08/23/2021] [Accepted: 08/25/2021] [Indexed: 12/28/2022] Open
Abstract
Using the method of dissipative particle dynamics (DPD) simulations, we investigated the interfacial properties of PEO/PEO-PPO-PEO/PPO ternary blends composed of the Pluronics L64(EO13PO30EO13), F68(EO76PO29EO76), F88(EO104PO39EO104), or F127(EO106PO70EO106) triblock copolymers. Our simulations show that: (i) The interfacial tensions (γ) of the ternary blends obey the relationship γF68 < γL64 < γF88 < γF127, which indicates that triblock copolymer F68 is most effective in reducing the interfacial tension, compared to L64, F88, and F127; (ii) For the blends of PEO/L64/PPO and the F64 copolymer concentration ranging from ccp = 0.2 to 0.4, the interface exhibits a saturation state, which results in the aggregation and micelle formation of F64 copolymers added to the blends, and a lowered efficiency of the L64 copolymers as a compatibilizer, thus, the interfacial tension decreases slightly; (iii) For the blends of PEO/F68/PPO, elevating the Pluronic copolymer concentration can promote Pluronic copolymer enrichment at the interfaces without forming the micelles, which reduces the interfacial tension significantly. The interfacial properties of the blends contained the PEO-PPO-PEO triblock copolymer compatibilizers are, thus, controlled by the triblock copolymer structure and the concentration. This work provides important insights into the use of the PEO-PPO-PEO triblock copolymer as compatibilizers in the PEO and PPO homopolymer blend systems.
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Understanding the Therapeutic Potential of Ascorbic Acid in the Battle to Overcome Cancer. Biomolecules 2021; 11:biom11081130. [PMID: 34439796 PMCID: PMC8392841 DOI: 10.3390/biom11081130] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2021] [Revised: 07/22/2021] [Accepted: 07/28/2021] [Indexed: 02/06/2023] Open
Abstract
Cancer, a fatal disease, is also one of the main causes of death worldwide. Despite various developments to prevent and treat cancer, the side effects of anticancer drugs remain a major concern. Ascorbic acid is an essential vitamin required by our bodies for normal physiological function and also has antioxidant and anticancer activity. Although the body cannot synthesize ascorbic acid, it is abundant in nature through foods and other natural sources and also exists as a nutritional food supplement. In anticancer drug development, ascorbic acid has played an important role by inhibiting the development of cancer through various mechanisms, including scavenging reactive oxygen species (ROS), selectively producing ROS and encouraging their cytotoxicity against tumour cells, preventing glucose metabolism, serving as an epigenetic regulator, and regulating the expression of HIF in tumour cells. Several ascorbic acid analogues have been produced to date for their anticancer and antioxidant activity. The current review summarizes the mechanisms behind ascorbic acid's antitumor activity, presents a compilation of its derivatives and their biological activity as anticancer agents, and discusses delivery systems such as liposomes, nanoparticles against cancer, and patents on ascorbic acid as anticancer agents.
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Phadke A, Amin P. A Recent Update on Drug Delivery Systems for Pain Management. J Pain Palliat Care Pharmacother 2021; 35:175-214. [PMID: 34157247 DOI: 10.1080/15360288.2021.1925386] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Pain remains a global health challenge affecting approximately 1.5 billion people worldwide. Pain has been an implicit variable in the equation of human life for many centuries considering different types and the magnitude of pain. Therefore, developing an efficacious drug delivery system for pain management remains an open challenge for researchers in the field of medicine. Lack of therapeutic efficacy still persists, despite high throughput studies in the field of pain management. Research scientists have been exploiting different alternatives to curb the adverse side effects of pain medications or attempting a more substantial approach to minimize the prevalence of pain. Various drug delivery systems have been developed such as nanoparticles, microparticles to curb adverse side effects of pain medications or minimize the prevalence of pain. This literature review firstly provides a brief introduction of pain as a sensation and its pharmacological interventions. Second, it highlights the most recent studies in the pharmaceutical field for pain management and serves as a strong base for future developments. Herein, we have classified drug delivery systems based on their sizes such as nano, micro, and macro systems, and for each of the reviewed systems, design, formulation strategies, and drug release performance has been discussed.
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Park SI, Song HM. Several Shapes of Single Crystalline Gold Nanomaterials Prepared in the Surfactant Mixture of CTAB and Pluronics. ACS OMEGA 2021; 6:3625-3636. [PMID: 33585743 PMCID: PMC7877706 DOI: 10.1021/acsomega.0c05166] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 10/23/2020] [Accepted: 01/14/2021] [Indexed: 06/12/2023]
Abstract
Twin structures in gold nanomaterials are destined because they reduce the severe strains in the misfit region of nanostructures. Defect-free single crystalline plasmonic nanomaterials gain interests these days as the integration of plasmonic materials or plasmons into electronic devices and circuits becomes more common. In this study, without subtle experimental adjustments, such as pH or halide additives, several shapes of single crystalline gold nanoparticles (NPs) are prepared in the surfactant mixture of cetyltrimethylammonium bromide (CTAB) and Pluronic triblock copolymers. The synthesized NPs are primarily composed of {100} planes with small numbers of particles possessing a [110] zone axis. Pluronic copolymers with low number average molecular weights (M n), such as L-31 (M n ≈ 1100) and L-64 (M n ≈ 2900), prefer anisotropic nanorods with the aspect ratios of 4.3 and 3.0, respectively, while Pluronics with high M n values, such as F-68 (M n ≈ 8400) and F-108 (M n ≈ 14 600), favor more concentric and isotropic cube-like NPs. Extended micelles are believed to form in Pluronics with low M n values in which hydrophobic cores are merged with the increase of temperature, while the corona regions that are composed of long tails of PEO prevent the merge of hydrophobic cores, and the growth of the micelles is limited in Pluronic copolymers with high M n values. The catalytic degradation reactions of methyl orange are conducted, and rather than isotropic particles, gold nanorods exhibit better catalytic performances. More hydrophilic environment and the steric alignment of rigid aromatic structures of methyl orange along the nanorods are thought to contribute to the catalytic activities. Overall, highly confined geometries of the appropriately swollen micellar templates of Pluronics and CTAB, which is not so hydrophobic as for the formation of contracted deswollen templates and for the inhibition of the growth of NPs, and which is not so hydrophilic as for the formation of coarse templates and for the formation of isotropic spheres with varying sizes, are believed as the main factor for the formation of single crystalline gold NPs.
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Gregoriou Y, Gregoriou G, Yilmaz V, Kapnisis K, Prokopi M, Anayiotos A, Strati K, Dietis N, Constantinou AI, Andreou C. Resveratrol loaded polymeric micelles for theranostic targeting of breast cancer cells. Nanotheranostics 2021; 5:113-124. [PMID: 33391978 PMCID: PMC7738945 DOI: 10.7150/ntno.51955] [Citation(s) in RCA: 45] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2020] [Accepted: 11/10/2020] [Indexed: 11/13/2022] Open
Abstract
Treatment of breast cancer underwent extensive progress in recent years with molecularly targeted therapies. However, non-specific pharmaceutical approaches (chemotherapy) persist, inducing severe side-effects. Phytochemicals provide a promising alternative for breast cancer prevention and treatment. Specifically, resveratrol (res) is a plant-derived polyphenolic phytoalexin with potent biological activity but displays poor water solubility, limiting its clinical use. Here we have developed a strategy for delivering res using a newly synthesized nano-carrier with the potential for both diagnosis and treatment. Methods: Res-loaded nanoparticles were synthesized by the emulsion method using Pluronic F127 block copolymer and Vitamin E-TPGS. Nanoparticle characterization was performed by SEM and tunable resistive pulse sensing. Encapsulation Efficiency (EE%) and Drug Loading (DL%) content were determined by analysis of the supernatant during synthesis. Nanoparticle uptake kinetics in breast cancer cell lines MCF-7 and MDA-MB-231 as well as in MCF-10A breast epithelial cells were evaluated by flow cytometry and the effects of res on cell viability via MTT assay. Results: Res-loaded nanoparticles with spherical shape and a dominant size of 179±22 nm were produced. Res was loaded with high EE of 73±0.9% and DL content of 6.2±0.1%. Flow cytometry revealed higher uptake efficiency in breast cancer cells compared to the control. An MTT assay showed that res-loaded nanoparticles reduced the viability of breast cancer cells with no effect on the control cells. Conclusions: These results demonstrate that the newly synthesized nanoparticle is a good model for the encapsulation of hydrophobic drugs. Additionally, the nanoparticle delivers a natural compound and is highly effective and selective against breast cancer cells rendering this type of nanoparticle an excellent candidate for diagnosis and therapy of difficult to treat mammary malignancies.
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Affiliation(s)
- Yiota Gregoriou
- Department of Biological Sciences, Faculty of Pure and Applied Sciences, University of Cyprus, Nicosia, Cyprus.,Department of Electrical and Computer Engineering University of Cyprus, Nicosia, Cyprus.,Emphasis Research Centre, University of Cyprus, Nicosia, Cyprus
| | - Gregoria Gregoriou
- Department of Biological Sciences, Faculty of Pure and Applied Sciences, University of Cyprus, Nicosia, Cyprus
| | - Vural Yilmaz
- Department of Biological Sciences, Faculty of Pure and Applied Sciences, University of Cyprus, Nicosia, Cyprus
| | - Konstantinos Kapnisis
- Department of Mechanical Engineering and Material Science and Engineering, Cyprus University of Technology, Limassol, Cyprus
| | - Marianna Prokopi
- Department of Mechanical Engineering and Material Science and Engineering, Cyprus University of Technology, Limassol, Cyprus
| | - Andreas Anayiotos
- Department of Mechanical Engineering and Material Science and Engineering, Cyprus University of Technology, Limassol, Cyprus
| | - Katerina Strati
- Department of Biological Sciences, Faculty of Pure and Applied Sciences, University of Cyprus, Nicosia, Cyprus
| | | | - Andreas I Constantinou
- Department of Biological Sciences, Faculty of Pure and Applied Sciences, University of Cyprus, Nicosia, Cyprus
| | - Chrysafis Andreou
- Department of Electrical and Computer Engineering University of Cyprus, Nicosia, Cyprus.,Emphasis Research Centre, University of Cyprus, Nicosia, Cyprus
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Abstract
Nanotechnology has been widely applied to medical interventions for prevention, diagnostics, and therapeutics of diseases, and the application of nanotechnology for medical purposes, which is called as a term "nanomedicine" has received tremendous attention. In particular, the design and development of nanoparticle for biosensors have received a great deal of attention, since those are most impactful area of clinical translation showing potential breakthrough in early diagnosis of diseases such as cancers and infections. For example, the nanoparticles that have intrinsic unique features such as magnetic responsive characteristics or photoluminescence can be utilized for noninvasive visualization of inner body. Drug delivery that makes use of drug-containing nanoparticles as a carrier is another field of study, in which the particulate form nanomedicine is given by parenteral administration for further systemic targeting to pathological tissues. In addition, encapsulation into nanoparticles gives the opportunity to secure the sensitive therapeutic payloads that are readily degraded or deactivated until reached to the target in biological environments, or to provide sufficient solubilization (e.g., to deliver compounds which have physicochemical properties that strongly limit their aqueous solubility and therefore systemic bioavailability). The nanomedicine is further intended to enhance the targeting index such as increased specificity and reduced false binding, thus improve the diagnostic and therapeutic performances. In this chapter, principles of nanomaterials for medicine will be thoroughly covered with applications for imaging-based diagnostics and therapeutics.
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Affiliation(s)
- Jinmyoung Joo
- Department of Biomedical Engineering, Ulsan National Institute of Science and Technology, Ulsan, South Korea.
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39
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Tipa C, Cidade MT, Vieira T, Silva JC, Soares PIP, Borges JP. A New Long-Term Composite Drug Delivery System Based on Thermo-Responsive Hydrogel and Nanoclay. NANOMATERIALS (BASEL, SWITZERLAND) 2020; 11:E25. [PMID: 33374282 PMCID: PMC7824189 DOI: 10.3390/nano11010025] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/04/2020] [Revised: 12/17/2020] [Accepted: 12/22/2020] [Indexed: 05/08/2023]
Abstract
Several problems and limitations faced in the treatment of many diseases can be overcome by using controlled drug delivery systems (DDS), where the active compound is transported to the target site, minimizing undesirable side effects. In situ-forming hydrogels that can be injected as viscous liquids and jellify under physiological conditions and biocompatible clay nanoparticles have been used in DDS development. In this work, polymer-clay composites based on Pluronics (F127 and F68) and nanoclays were developed, aiming at a biocompatible and injectable system for long-term controlled delivery of methylene blue (MB) as a model drug. MB release from the systems produced was carried out at 37 °C in a pH 7.4 medium. The Pluronic formulation selected (F127/F68 18/2 wt.%) displayed a sol/gel transition at approx. 30 °C, needing a 2.5 N force to be injected at 25 °C. The addition of 2 wt.% of Na116 clay decreased the sol/gel transition to 28 °C and significantly enhanced its viscoelastic modulus. The most suitable DDS for long-term application was the Na116-MB hybrid from which, after 15 days, only 3% of the encapsulated MB was released. The system developed in this work proved to be injectable, with a long-term drug delivery profile up to 45 days.
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Affiliation(s)
- Cezar Tipa
- CENIMAT/I3N, Departamento de Ciência dos Materiais, Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa, 2829-516 Caparica, Portugal;
| | - Maria T. Cidade
- CENIMAT/I3N, Departamento de Ciência dos Materiais, Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa, 2829-516 Caparica, Portugal;
| | - Tânia Vieira
- CENIMAT/I3N, Departamento de Física, Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa, 2829-516 Caparica, Portugal; (T.V.); (J.C.S.)
| | - Jorge Carvalho Silva
- CENIMAT/I3N, Departamento de Física, Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa, 2829-516 Caparica, Portugal; (T.V.); (J.C.S.)
| | - Paula I. P. Soares
- CENIMAT/I3N, Departamento de Ciência dos Materiais, Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa, 2829-516 Caparica, Portugal;
| | - João Paulo Borges
- CENIMAT/I3N, Departamento de Ciência dos Materiais, Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa, 2829-516 Caparica, Portugal;
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40
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Morrison KA, Weinreb RH, Dong X, Toyoda Y, Jin JL, Bender R, Mukherjee S, Spector JA. Facilitated self-assembly of a prevascularized dermal/epidermal collagen scaffold. Regen Med 2020; 15:2273-2283. [PMID: 33325258 DOI: 10.2217/rme-2020-0070] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023] Open
Abstract
Introduction: Resurfacing complex full thickness wounds requires free tissue transfer which creates donor site morbidity. We describe a method to fabricate a skin flap equivalent with a hierarchical microvascular network. Materials & methods: We fabricated a flap of skin-like tissue containing a hierarchical vascular network by sacrificing Pluronic® F127 macrofibers and interwoven microfibers within collagen encapsulating human pericytes and fibroblasts. Channels were seeded with smooth muscle and endothelial cells. Constructs were topically seeded with keratinocytes. Results: After 28 days in culture, multiphoton microscopy revealed a hierarchical interconnected network of macro- and micro-vessels; larger vessels (>100 μm) were lined with a monolayer endothelial neointima and a subendothelial smooth muscle neomedia. Neoangiogenic sprouts formed in the collagen protodermis and pericytes self-assembled around both fabricated vessels and neoangiogenic sprouts. Conclusion: We fabricated a prevascularized scaffold containing a hierarchical 3D network of interconnected macro- and microchannels within a collagen protodermis subjacent to an overlying protoepidermis with the potential for recipient microvascular anastomosis.
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Affiliation(s)
- Kerry A Morrison
- Department of Surgery, Laboratory of Bioregenerative Medicine & Surgery, Division of Plastic Surgery, Weill Cornell Medical College, New York, NY 10021, USA.,Plastic Surgery Resident Physician affiliated with the Hansjorg Wyss Department of Plastic Surgery, New York University Langone Medical Center, New York, NY 10016, USA
| | - Ross H Weinreb
- Department of Surgery, Laboratory of Bioregenerative Medicine & Surgery, Division of Plastic Surgery, Weill Cornell Medical College, New York, NY 10021, USA
| | - Xue Dong
- Department of Surgery, Laboratory of Bioregenerative Medicine & Surgery, Division of Plastic Surgery, Weill Cornell Medical College, New York, NY 10021, USA
| | - Yoshiko Toyoda
- Department of Surgery, Laboratory of Bioregenerative Medicine & Surgery, Division of Plastic Surgery, Weill Cornell Medical College, New York, NY 10021, USA.,Plastic Surgery Resident Physician affiliated with the Division of Plastic Surgery, University of Pennsylvania, Philadelphia, PA 19104, USA
| | - Julia L Jin
- Department of Surgery, Laboratory of Bioregenerative Medicine & Surgery, Division of Plastic Surgery, Weill Cornell Medical College, New York, NY 10021, USA
| | - Ryan Bender
- Department of Surgery, Laboratory of Bioregenerative Medicine & Surgery, Division of Plastic Surgery, Weill Cornell Medical College, New York, NY 10021, USA
| | - Sushmita Mukherjee
- Department of Biochemistry, Weill Cornell Medical College, New York, NY 14850, USA
| | - Jason A Spector
- Department of Surgery, Laboratory of Bioregenerative Medicine & Surgery, Division of Plastic Surgery, Weill Cornell Medical College, New York, NY 10021, USA.,Nancy E. & Peter C. Meinig School of Bioengineering, Cornell University, Ithaca, NY 14850, USA
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41
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Jarak I, Varela CL, Tavares da Silva E, Roleira FFM, Veiga F, Figueiras A. Pluronic-based nanovehicles: Recent advances in anticancer therapeutic applications. Eur J Med Chem 2020; 206:112526. [PMID: 32971442 DOI: 10.1016/j.ejmech.2020.112526] [Citation(s) in RCA: 33] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2019] [Revised: 05/27/2020] [Accepted: 06/01/2020] [Indexed: 02/06/2023]
Abstract
Pluronics are a class of amphiphilic tri-block copolymers with wide pharmaceutical applicability. In the past decades, the ability to form biocompatible nanosized micelles was exploited to formulate stable drug nanovehicles with potential use in antitumor therapy. Due to the great potential for tuning physical and structural properties of Pluronic unimers, a panoply of drug or polynucleotide-loaded micelles was prepared and tested for their antitumoral activity. The attractive inherent antitumor properties of Pluronic polymers in combination with cell targeting and stimuli-responsive ligands greatly improved antitumoral therapeutic effects of tested drugs. In spite of that, the extraordinary complexity of biological challenges in the delivery of micellar drug payload makes their therapeutic potential still not exploited to the fullest. In this review paper we attempt to present the latest developments in the field of Pluronic based nanovehicles and their application in anticancer therapy with an overview of the chemistry involved in the preparation of these nanovehicles.
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Affiliation(s)
- Ivana Jarak
- Univ. Coimbra, Department of Pharmaceutical Technology, Faculty of Pharmacy, Azinhaga de Santa Comba, Pólo III - Pólo das Ciências da Saúde, 3000-548, Coimbra, Portugal
| | - Carla L Varela
- Univ. Coimbra, CIEPQPF, FFUC, Laboratory of Pharmaceutical Chemistry, Azinhaga de Santa Comba, Pólo III - Pólo das Ciências da Saúde, 3000-548, Coimbra, Portugal
| | - Elisiário Tavares da Silva
- Univ. Coimbra, CIEPQPF, FFUC, Laboratory of Pharmaceutical Chemistry, Azinhaga de Santa Comba, Pólo III - Pólo das Ciências da Saúde, 3000-548, Coimbra, Portugal
| | - Fernanda F M Roleira
- Univ. Coimbra, CIEPQPF, FFUC, Laboratory of Pharmaceutical Chemistry, Azinhaga de Santa Comba, Pólo III - Pólo das Ciências da Saúde, 3000-548, Coimbra, Portugal
| | - Francisco Veiga
- Univ. Coimbra, Department of Pharmaceutical Technology, Faculty of Pharmacy, Azinhaga de Santa Comba, Pólo III - Pólo das Ciências da Saúde, 3000-548, Coimbra, Portugal; Univ. Coimbra, REQUIMTE/LAQV, Group of Pharmaceutical Technology, Faculty of Pharmacy, Azinhaga de Santa Comba, Pólo III - Pólo das Ciências da Saúde, 3000-548, Coimbra, Portugal
| | - Ana Figueiras
- Univ. Coimbra, Department of Pharmaceutical Technology, Faculty of Pharmacy, Azinhaga de Santa Comba, Pólo III - Pólo das Ciências da Saúde, 3000-548, Coimbra, Portugal; Univ. Coimbra, REQUIMTE/LAQV, Group of Pharmaceutical Technology, Faculty of Pharmacy, Azinhaga de Santa Comba, Pólo III - Pólo das Ciências da Saúde, 3000-548, Coimbra, Portugal.
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42
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Kurnik IS, Mussagy CU, Pereira JF, Lopes AM. Amphiphilic copolymer aqueous solutions with cholinium ionic liquids as adjuvants: New insights into determination of binodal curves and phase-separation mechanisms. J Mol Liq 2020. [DOI: 10.1016/j.molliq.2020.114245] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
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43
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Influence of surfactant's polar head group charge on the self-assembly of three PEO–PPO–PEO triblock copolymers of widely varying hydrophobicity. J Mol Liq 2020. [DOI: 10.1016/j.molliq.2020.113858] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
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44
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Dimitrijević A, Tavares APM, Jocić A, Marić S, Trtić-Petrović T, Gadžurić S, Freire MG. Aqueous biphasic systems comprising copolymers and cholinium-based salts or ionic liquids: Insights on the mechanisms responsible for their creation. Sep Purif Technol 2020. [DOI: 10.1016/j.seppur.2020.117050] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
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45
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Kamble S, Varamini P, Müllner M, Pelras T, Rohanizadeh R. Bisphosphonate-functionalized micelles for targeted delivery of curcumin to metastatic bone cancer. Pharm Dev Technol 2020; 25:1118-1126. [DOI: 10.1080/10837450.2020.1798458] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Affiliation(s)
- Sumedh Kamble
- School of Pharmacy, University of Sydney, Sydney, Australia
| | - Pegah Varamini
- School of Pharmacy, University of Sydney, Sydney, Australia
| | - Markus Müllner
- Key Centre for Polymers and Colloids, School of Chemistry, University of Sydney, Sydney, Australia
| | - Théophile Pelras
- Key Centre for Polymers and Colloids, School of Chemistry, University of Sydney, Sydney, Australia
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46
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Russo E, Villa C. Poloxamer Hydrogels for Biomedical Applications. Pharmaceutics 2019; 11:E671. [PMID: 31835628 PMCID: PMC6955690 DOI: 10.3390/pharmaceutics11120671] [Citation(s) in RCA: 236] [Impact Index Per Article: 39.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2019] [Revised: 11/25/2019] [Accepted: 12/06/2019] [Indexed: 11/23/2022] Open
Abstract
This review article focuses on thermoresponsive hydrogels consisting of poloxamers which are of high interest for biomedical application especially in drug delivery for ophthalmic, injectable, transdermal, and vaginal administration. These hydrogels remain fluid at room temperature but become more viscous gel once they are exposed to body temperature. In this way, the gelling system remains at the topical level for a long time and the drug release is controlled and prolonged. Poloxamers are synthetic triblock copolymers of poly(ethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide) (PEO-PPO-PEO), also commercially known as Pluronics®, Synperonics® or Lutrol®. The different poloxamers cover a range of liquids, pastes, and solids, with molecular weights and ethylene oxide-propylene oxide weight ratios varying from 1100 to 14,000 and 1:9 to 8:2, respectively. Concentrated aqueous solutions of poloxamers form thermoreversible gels. In recent years this type of gel has arouse interest for tissue engineering. Finally, the use of poloxamers as biosurfactants is evaluated since they are able to form micelles in an aqueous environment above a concentration threshold known as critical micelle concentration (CMC). This property is exploited for drug delivery and different therapeutic applications.
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Affiliation(s)
- Eleonora Russo
- Department of Pharmacy, University of Genoa, Viale Benedetto XV, 16132 Genova, Italy;
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47
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He Y, Liu Y, Sun Z, Han F, Tang JZ, Gao R, Wang G. The proper strategy to compress and protect plasmid DNA in the Pluronic L64-electropulse system for enhanced intramuscular gene delivery. Regen Biomater 2019; 6:289-298. [PMID: 31616566 PMCID: PMC6783702 DOI: 10.1093/rb/rby028] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2018] [Revised: 10/30/2018] [Accepted: 11/26/2018] [Indexed: 12/14/2022] Open
Abstract
Intramuscular expression of functional proteins is a promising strategy for therapeutic purposes. Previously, we developed an intramuscular gene delivery method by combining Pluronic L64 and optimized electropulse, which is among the most efficient methods to date. However, plasmid DNAs (pDNAs) in this method were not compressed, making them unstable and inefficient in vivo. We considered that a proper compression of pDNAs by an appropriate material should facilitate gene expression in this L64-electropulse system. Here, we reported our finding of such a material, Epigallocatechin gallate (EGCG), a natural compound in green teas, which could compress and protect pDNAs and significantly increase intramuscular gene expression in the L64-electropulse system. Meanwhile, we found that polyethylenimine (PEI) could also slightly improve exogenous gene expression in the optimal procedure. By analysing the characteristic differences between EGCG and PEI, we concluded that negatively charged materials with strong affinity to nucleic acids and/or other properties suitable for gene delivery, such as EGCG, are better alternatives than cationic materials (like PEI) for muscle-based gene delivery. The results revealed that a critical principle for material/pDNA complex benefitting intramuscular gene delivery/expression is to keep the complex negatively charged. This proof-of-concept study displays the breakthrough in compressing pDNAs and provides a principle and strategy to develop more efficient intramuscular gene delivery systems for therapeutic applications.
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Affiliation(s)
- Yutong He
- National Engineering Research Center for Biomaterials
| | - Yili Liu
- National Engineering Research Center for Biomaterials
- Key Laboratory for Bio-Resource and Eco-Environment of Ministry Education, College of Life Science, Sichuan University, No. 29, Wangjiang Road, Chengdu, Sichuan, P.R. China
| | - Zhe Sun
- National Engineering Research Center for Biomaterials
| | - Fei Han
- National Engineering Research Center for Biomaterials
| | - James Zhenggui Tang
- Research Institute in Healthcare Science, Faculty of Science and Engineering, School of Pharmacy, University of Wolverhampton, Wolverhampton, UK
| | - Rong Gao
- Key Laboratory for Bio-Resource and Eco-Environment of Ministry Education, College of Life Science, Sichuan University, No. 29, Wangjiang Road, Chengdu, Sichuan, P.R. China
| | - Gang Wang
- National Engineering Research Center for Biomaterials
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48
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Shah E, Kadam A, Jubin T, Begum R, Upadhyay P, Soni HP. EDTA‐Capped Iron Oxide Core‐Corona System as Vehicle for Gene Delivery to Transform
E.coli
: Mimicking the Lipid Bilayer Environment. ChemistrySelect 2019. [DOI: 10.1002/slct.201900964] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Affiliation(s)
- Ekta Shah
- Department of ChemistryFaculty of Science, The Maharaja Sayajirao University of Baroda Vadodara- 390 002, Gujarat India
| | - Ashlesha Kadam
- Department of BiochemistryFaculty of ScienceThe Maharaja Sayajirao University of Baroda Vadodara- 390 002, Gujarat India
| | - Tina Jubin
- Department of BiochemistryFaculty of ScienceThe Maharaja Sayajirao University of Baroda Vadodara- 390 002, Gujarat India
| | - Rasheedunnisa Begum
- Department of BiochemistryFaculty of ScienceThe Maharaja Sayajirao University of Baroda Vadodara- 390 002, Gujarat India
| | - Pratik Upadhyay
- Department of Pharmaceutical TechnologyL. J. Institute of Pharmacy, Ahmedabad, Gujarat India
| | - Hemant P. Soni
- Department of ChemistryFaculty of Science, The Maharaja Sayajirao University of Baroda Vadodara- 390 002, Gujarat India
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49
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Filip D, Macocinschi D, Vlad S, Ibănescu C, Danu M, Zaltariov MF. Micellar and rheological properties of some sodium deoxycholate-based poly(ester ether)urethane ionomer biomaterials in N,N-dimethylformamide solutions. J Mol Liq 2019. [DOI: 10.1016/j.molliq.2019.04.122] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
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50
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Mora AK, Basu A, Kalel R, Nath S. Polymer-assisted drug sequestration from plasma protein by a surfactant with curtailed denaturing capacity. Phys Chem Chem Phys 2019; 21:7127-7136. [PMID: 30887975 DOI: 10.1039/c8cp03576h] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
The capability of a surfactant to sequester a drug bound to plasma protein was investigated using steady-state and time-resolved spectroscopic techniques. Surfactants are known to denature protein, and hence are not suitable for the sequestration of a drug from protein. Herein, we show that the denaturing capacity of a surfactant is curtailed completely and its drug sequestration power is enhanced in the presence of biocompatible Pluronic micelles due to the formation of unique supramolecular assemblies. Further, our detailed studies indicate that the concentration of surfactant required for the sequestration of a drug is less than its critical micellar concentration (CMC). The extent of sequestration of drug by polymer-surfactant supramolecular assemblies can be tuned finely by controlling the concentration of surfactant. Detailed analysis showed that up to ∼85% sequestration of a drug from plasma protein could be achieved using a sub-CMC concentration of surfactant. Our results clearly show that controlled sequestration of a drug from plasma protein can be achieved with a reduction in the protein denaturing properties of surfactants.
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Affiliation(s)
- Aruna K Mora
- Radiation & Photochemistry Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400 085, India.
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