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Folate Conjugated Polymer Micelles Formulated with TPGS for Selective Tumor Targeting

Haizheng Zhao and Lin Yue Lanry Yung. Department of Chemical and Biomolecular Engineering, National University of Singapore, Singapore, Singapore

Folate conjugated polymer micelles poly(DL-lactide-co-glycolide)-poly(ethylene glycol)-folate was synthesized to encapsulate anticancer drug doxorubicin (DOX) to achieve targeting delivery. In order to increase the therapeutic effect, d--tocopheryl polyethylene glycol 1000 succinate (TPGS) was added during the micelles preparation. The effects of TPGS on the properties of folate conjugated micelles (PLGA-PEG-FOL) were studied, such as physicochemical properties, drug release, cytotoxicity, cellular uptake, cell cycle and apoptosis. The characterization study showed that adding TPGS did not result in much variation in the micellar size, surface charge and drug encapsulation efficiency. The cytotoxicity study showed that TPGS significantly increased the cytotoxicity of drug-loaded micelles on KB cells and the effect was concentration dependent. In contrast, the addition of TPGS to the micelles showed minimal cytotoxicity enhancement on the normal fibroblasts compared with the micelles without TPGS. These results demonstrated that TPGS exhibited selective cytotoxicity between cancerous cells and normal cells. Cell uptake study showed that DOX-loaded PLGA-PEG-FOL micelles with 10% TPGS had higher cellular uptake compared with the ones formulated without TPGS. Both the cell cycle and apoptosis assays demonstrated that TPGS enhanced the absorption of drug-loaded polymer micelles and increased the concentration of DOX in tumor cells. Therefore, this new formulation with TPGS could be promising in improving the therapeutic efficacy of polymer micellar targeting delivery system.