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  • Title: Addition of TPGS to folate-conjugated polymer micelles for selective tumor targeting.
    Author: Zhao H, Yung LY.
    Journal: J Biomed Mater Res A; 2009 Nov; 91(2):505-18. PubMed ID: 18985763.
    Abstract:
    Folate-conjugated polymer micelles poly(D,L-lactide-co-glycolide)-poly(ethylene glycol)-folate (PLGA-PEG-FOL) was fabricated to encapsulate anticancer drug doxorubicin for targeting delivery to cancer cells with overexpression of folate receptors. To increase therapeutic effect, D-alpha-tocopheryl polyethylene glycol succinate (TPGS) was added during the micelles preparation. The physicochemical study showed that the mixed micelles of PLGA-PEG-FOL and TPGS formed a homogeneous population. The addition of TPGS did not result in much variation in the micellar size, surface charge, and drug encapsulation efficiency. The cellular uptake study showed that mixed micelles with TPGS had higher cellular uptake compared with the ones without TPGS to drug-resistant cancer cells. These mixed micelles also selectively increased the cytotoxicity of drug on cancer cells but exhibited minimal cytotoxic enhancement on normal fibroblasts. Furthermore, the accumulation of rhodamine study showed that the mixed micelles with TPGS increased the cellular uptake of drugs on Caco-2 cells. This indicates that TPGS in the mixed micelles may act as P-glycoprotein inhibitor to reduce drug efflux. This new formulation with TPGS may have dual functions of folate-mediated targeting and multidrug resistance inhibition and can be promising in improving the therapeutic efficacy of polymer micellar targeting delivery system.
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