title: Fabrication of cationic nanomicelle from chitosan-graft-polycaprolactone as the carrier of 7-ethyl-10-hydroxy-camptothecin.
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 epsilon-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.
authors.affiliation: Institutes for Advanced Interdisciplinary Research, East China Normal University, and Department of Diagnostic Imaging, Changzheng Hospital, Shanghai 200062, PR China.
authors.forename: Kongrong
authors.initials: K
authors.lastname: Duan
authors.forename: Xiaolan
authors.initials: X
authors.lastname: Zhang
authors.forename: Xiaoxing
authors.initials: X
authors.lastname: Tang
authors.forename: Jiahui
authors.initials: J
authors.lastname: Yu
authors.forename: Shiyuan
authors.initials: S
authors.lastname: Liu
authors.forename: Daxin
authors.initials: D
authors.lastname: Wang
authors.forename: Yaping
authors.initials: Y
authors.lastname: Li
authors.forename: Jin
authors.initials: J
authors.lastname: Huang
mesh_terms: D002166:Camptothecin / Q000031:analogs & derivatives* / Q000737:chemistry; D002412:Cations / Q000737:chemistry; D048271:Chitosan / Q000737:chemistry*; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry*; D000077146:Irinotecan; D008823:Micelles; D049329:Nanostructures / Q000737:chemistry*; D010316:Particle Size; D011091:Polyesters / Q000737:chemistry*; D013499:Surface Properties
chemical_list: D002412:Cations; D004337:Drug Carriers; D008823:Micelles; D011091:Polyesters; C016240:polycaprolactone; D000077146:Irinotecan; D048271:Chitosan; D002166:Camptothecin