Design and Characterization of PEG-Derivatized Vitamin E as a Nanomicellar Formulation for Delivery of Paclitaxel

作者：Lu Jianqin; Huang Yixian; Zhao Wenchen; Chen Yichao; Li Jiang; Gao Xiang; Venkataramanan Raman; Li Song^*

来源：Molecular Pharmaceutics, 2013, 10(8): 2880-2890.

DOI：10.1021/mp300729y

• nanomicelles
• paclitaxel
• TPGS
• controlled and sustained drug delivery
• cancer
• nanotechnology

Various PEG Vitamin E conjugates including D-a-tocopheryl poly(ethylene glycol) succinate 1000 (TPGS) have been extensively studied as a nonionic surfactant in various drug delivery systems However, limited information is available about the structure activity relationship of PEG Vitamin E conjugates as a micellar formulation for paclitaxel (PTX). In this study, four PEG Vitamin E conjugates were developed that vary in the molecular weight of PEG (PEG(2K) vs PEG(5K)) and the molar ratio of PEG/Vitamin E (1/1 vs 1/2) in the conjugates These conjugates were systematically characterized with respect to CMC, PTX loading efficiency, stability, and their efficiency in delivery of PTX to tumor cells in vitro and in vivo. Our data show that PEG(5K)-conjugates have lower CMC values and are more effective in PTX loading with respect to both loading capacity and stability. The conjugates with two Vitamin E molecules also worked better than the conjugates with one molecule of Vitamin E, particularly for PEG(2K)-system. Furthermore, all of the PEG Vitamin E conjugates can induce significant suppression of P-gp function. More importantly, PTX-loaded PEG(5K)-VE2 resulted in significantly improved tumor growth inhibitory effect in comparison to PTX formulated in PEG(2K)-VE or PEG(2K)-VE nu as well as Cremophor EL (Taxol) in a syngeneic mouse model of breast cancer (4T1.2). Our study suggests that PEG(5K)-Vitmin E-2 may hold promise as an Unproved micellar formulation for in vivo delivery of anticancer agents such as PTX.

• 出版日期2013-8