Fabrication of cationic nanomicelle from chitosan-graft-polycaprolactone as the carrier of 7-ethyl-10-hydroxy-camptothecin |
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| Institution: | 1. Institutes for Advanced Interdisciplinary Research, East China Normal University, Shanghai 200062, PR China;2. College of Chemical Engineering, Wuhan University of Technology, Wuhan 430070, PR China;3. Department of Diagnostic Imaging, Changzheng Hospital, Shanghai 200003, PR China;4. Subei Hospital of Jiangsu Province, Yangzhou University, Yangzhou 225001, PR China;5. Center for Drug Delivery System, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, PR China;1. Department of Physics, Faculty of Arts and Sciences, Ondokuz Mayis University, 55139, Kurupelit, Samsun, Turkey;2. Department of Chemistry, Faculty of Science, Karamanoglu Mehmetbey University, 70200 Karaman, Turkey;3. Department of Physics, Faculty of Sciences, Gazi University, 06500, Teknikokullar, Ankara, Turkey;4. Department of Chemistry, Faculty of Science, Firat University, 23119, Elazig, Turkey;1. Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal 576104, Karnataka State, India;2. Department of Clinical Embryology, Kasturba Medical College, Manipal University, Manipal 576104, Karnataka State, India;3. School of Pharmacy, Pharmacy Australia Centre of Excellence (PACE), The University of Queensland, Brisbane, QLD 4072, Australia;1. Clinical Pharmacokinetics Unit, Hospital de Pediatría JP Garrahan, Argentina;2. National Council of Scientific and Technical Research, CONICET, Argentina;3. Pharmacology Laboratory, CIVETAN-CONICET, Faculty of Veterinary Science, National University of the Center of Buenos Aires, Argentina;4. Department of Pharmaceutical Technology, Faculty of Pharmacy and Biochemistry, University of Buenos Aires, Argentina;5. Argentinean Foundation of Ophthalmology Jorge Malbrán, Buenos Aires, Argentina;6. Department of Pharmacology, Faculty of Pharmacy and Biochemistry, University of Buenos Aires, Argentina;7. Animal Facility Laboratory, Hospital de Pediatria J.P. Garrahan, Argentina;1. Department of Nanotechnology and Nanomedicine, Graduate School of Science and Engineering, Hacettepe University, Ankara, Turkey;2. Pharmaceutical Sciences Laboratory, Faculty of Science and Engineering, Åbo Akademi University, Turku, Finland;3. Department of Pharmaceutical Technology, Faculty of Pharmacy, Erciyes University, Kayseri, Turkey;4. Department of Pharmaceutical Technology, Faculty of Pharmacy, Hacettepe University, Ankara, Turkey |
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| Abstract: | In this research, amphiphilic brush-like polycations were synthesized, and used to fabricate cationic nanomicelle as the carrier of 7-ethyl-10-hydroxy-camptothecin (SN-38), in order to enhance its cellular uptake, solubility and stability in aqueous media. In particular, cationic chitosan-graft-polycaprolactone (CS-g-PCL) copolymers were synthesized with a facile one-pot manner via ring-opening polymerization of ɛ-CL onto the hydroxyl groups of CS by using methanesulfonic acid as solvent and catalyst. The formation of CS-g-PCL nanomicelles was confirmed by fluorescence spectrophotoscopy and particle size measurements. It was found that all the nanomicelles showed spherical shapes with narrow size distributions. Their sizes ranged from 47 to 113 nm, and the zeta potentials ranged from 26.7 to 50.8 mV, depending on the grafting content of PCL in CS-g-PCL, suggesting their passive targeting to tumor tissue and endocytosis potential. Water-insoluble antitumor drug, SN-38, was easily encapsulated into CS-g-PCL nanomicelles by lyophilization method. In comparison with bare CS-g-PCL nanomicelles, the corresponding SN-38-loaded nanomicelles showed increased particle sizes and a little reduced zeta potentials. With an increase of grafting PCL content, the drug encapsulation efficiency (EE) and drug loading (DL) of the nanomicelles increased from 64.3 to 84.6% and 6.43 to 8.66%, respectively, whereas their accumulative drug release showed a tendency to decrease due to the enhanced hydrophobic interaction between hydrophobic drug and hydrophobic PCL segments in CS-g-PCL. Also, the CS-g-PCL nanomicelles effectively protected the active lactone ring of SN-38 from hydrolysis under physiological condition, due to the encapsulation of SN-38 into the hydrophobic cores in the nanomicelles. Compared with free SN-38, the SN-38-loaded nanomicelles showed essential decreased cytotoxicity against L929 cell line, and bare CS-g-PCL nanomicelles almost showed non-toxicity. These results suggested the potential utilization of the CS-g-PCL nanomicelles as the carriers of hydrophobic drugs with improving the delivery and release properties. |
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