Coadministration of glycolipid-like micelles loading cytotoxic drug with different action site for efficient cancer chemotherapy.
To reduce the side effects and drug resistance in cancer chemotherapy, we have examined the in vitro efficacy of the combination of paclitaxel (PTX) and doxorubicin (DOX) loaded in nanosized polymeric micelles with glycolipid-like structure, which formed by lipid grafted chitosan. The cytotoxicities of PTX and DOX, either as single agents or in combination, were examined using drug sensitive tumor cells and drug resistant cells. It was found that the 50% inhibition of cellular growth (IC(50)) of PTX and DOX in micelles against drug sensitive cells was lowered about 20-fold and 4-7-fold compared to that of Taxol and DOX solution, respectively. The IC(50) of PTX and DOX in micelles against drug resistant cells was lowered more significantly, and no clear difference was found between drug sensitive and drug resistant cells. The coadministration of PTX and DOX in micelles showed a more conspicuous effect than that of micelles loaded with a single drug. The micelles presented excellent internalization to cancer cells, which results in increased intracellular accumulation of PTX and DOX in its molecular-target site. The coadministration of glycolipid-like micelles loaded with different cytotoxic drugs indicated synergistic effects for drug sensitive cells and drug resistant cells.
Women Hospital, School of Medicine, Zhejiang University, Hangzhou, People's Republic of China.
Meng-Dan
MD
Zhao
Fu-Qiang
FQ
Hu
Yong-Zhong
YZ
Du
Hong
H
Yuan
Feng-Ying
FY
Chen
Ya-Min
YM
Lou
He-Yong
HY
Yu
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000737:chemistry*; D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000473:pathology* / Q000503:physiopathology*; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage / Q000737:chemistry; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry*; D006017:Glycolipids / Q000737:chemistry*; D006801:Humans; D008823:Micelles; D017239:Paclitaxel / Q000008:administration & dosage / Q000737:chemistry
D004337:Drug Carriers; D006017:Glycolipids; D008823:Micelles; D004317:Doxorubicin; D017239:Paclitaxel