title: Improved cytotoxicity and multidrug resistance reversal of chitosan based polymeric micelles encapsulating oxaliplatin.
abstract: To overcome the side effects and drug resistance in cancer chemotherapy, oxaliplatin (OXA) was encapsulated in chitosan based polymeric micelles with glycolipid-like structure, which were formed by stearic acid-grafted chitosan oligosaccharide (CSO-SA). CSO-SA with 6.89% amino substituted degree was synthesized in this paper. The critical micelle concentration was about 0.12 mg/mL. CSO-SA micelles with the concentration of 1.0 mg/mL had 34.8 nm number average diameter and +50.8 mV surface potential in the aqueous medium. Thin-film dispersed method mediated by lecithin was chosen to prepare OXA-loaded CSO-SA micelles (CSO-SA/OXA), encapsulation efficiency of which could reach up to about 47%. In vitro anti-tumor activity of CSO-SA/OXA micelles against drug sensitive tumor cells and drug resistant cells was then examined. Using SGC-7901, SKOV3, BEL-7402, K562, and MCF-7 as model drug sensitive tumor cells, the 50% inhibition of cellular growth (IC(50)) of CSO-SA/OXA micelles could be lowered about 3-6 folds compared to that of free OXA solution. Furthermore, cytotoxicity test of CSO-SA/OXA micelles against MCF-7 and multidrug resistant MCF-7 (MCF-7/Adr) cells presented the reversal activity against MCF-7/Adr cells. The present micelles are a promising carrier candidate for platinum drug to improve the anti-tumor activity.
authors.affiliation: College of Pharmaceutical Science, Zhejiang University, Hangzhou, PR China.
authors.forename: Yang-Yan
authors.initials: YY
authors.lastname: Xu
authors.forename: Yong-Zhong
authors.initials: YZ
authors.lastname: Du
authors.forename: Hong
authors.initials: H
authors.lastname: Yuan
authors.forename: Li-Na
authors.initials: LN
authors.lastname: Liu
authors.forename: Yang-Ping
authors.initials: YP
authors.lastname: Niu
authors.forename: Fu-Qiang
authors.initials: FQ
authors.lastname: Hu
mesh_terms: D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D048271:Chitosan / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry*; D004339:Drug Compounding; D018432:Drug Resistance, Multiple / Q000187:drug effects*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D006801:Humans; D008823:Micelles; D046529:Microscopy, Electron, Transmission; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D000077150:Oxaliplatin; D010316:Particle Size; D013499:Surface Properties
chemical_list: D004337:Drug Carriers; D008823:Micelles; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D048271:Chitosan