Improved cytotoxicity and multidrug resistance reversal of chitosan based polymeric micelles encapsulating oxaliplatin.
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.
Xu
Yang-Yan
YY
College of Pharmaceutical Science, Zhejiang University, Hangzhou, PR China.
Du
Yong-Zhong
YZ
Yuan
Hong
H
Liu
Li-Na
LN
Niu
Yang-Ping
YP
Hu
Fu-Qiang
FQ
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
D004337:Drug Carriers; D008823:Micelles; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D048271:Chitosan