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  • Title: Improved cytotoxicity and multidrug resistance reversal of chitosan based polymeric micelles encapsulating oxaliplatin.
    Author: Xu YY, Du YZ, Yuan H, Liu LN, Niu YP, Hu FQ.
    Journal: J Drug Target; 2011 Jun; 19(5):344-53. PubMed ID: 20854014.
    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.
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