title: Thermosensitive micelles-hydrogel hybrid system based on poloxamer 407 for localized delivery of paclitaxel.
abstract: A thermosensitive micelles-hydrogel hybrid system based on Poloxamer 407 (P407) was prepared to resolve the fast erosion and low loading capability of lipophilic drug of P407 gels for local chemotherapy. Different amounts of glutaraldehyde (GA) were applied to generate cross-linked networks with carboxymethyl chitosan (CMCS) interpenetrated in P407 gels, in which paclitaxel (PTX)-loaded N-octyl-O-sulfate chitosan micelles (PTX-M) were dispersed uniformly. The in vitro characteristics of CMCS-modified P407 gels (PTX-M-MG) were performed by examining the viscosity, swelling ratio, mechanical property, and drug release, while the in vivo evaluation included tissue distribution and anticancer efficacy through intratumoral administration in hepatoma solidity cell (Heps) tumor-bearing mice. The results showed that PTX-M-MG containing 0.05% (w/v) GA possessed lower viscosity, higher swelling ratio, stronger mechanical property, and longer term drug release, in which the loading efficiency of PTX was enlarged by the introduction of PTX-M. Moreover, PTX-M-MG revealed a prolonged retention at tumor sites, lasting for 20 days, and a superior tumor inhibition rate (64.27%) with reduced toxicity compared with Taxol(®) , PTX-M, and PTX-M loaded unmodified P407 gels (PTX-M-P407). It can be concluded that PTX-M-MG is a promising local delivery system for hydrophobic drug in cancer therapy, providing both improved efficacy and relieved side effects.
authors.affiliation: Center of Drug Discovery, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, PR China.
authors.forename: Caoyun
authors.initials: C
authors.lastname: Ju
authors.forename: Juan
authors.initials: J
authors.lastname: Sun
authors.forename: Peng
authors.initials: P
authors.lastname: Zi
authors.forename: Xiang
authors.initials: X
authors.lastname: Jin
authors.forename: Can
authors.initials: C
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D048271:Chitosan / Q000031:analogs & derivatives / Q000737:chemistry; D003692:Delayed-Action Preparations / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems; D006801:Humans; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D051379:Mice; D008823:Micelles; D017239:Paclitaxel / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D020442:Poloxamer / Q000737:chemistry*; D012212:Rheology; D013696:Temperature
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D008823:Micelles; C528556:N-octyl-O-sulfate chitosan; C514968:carboxymethyl-chitosan; D020442:Poloxamer; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D048271:Chitosan; D017239:Paclitaxel
keywords: biomaterials; cancer chemotherapy; controlled release; hydrogels; localized delivery; micelles; poloxamer 407