期刊
DRUG DEVELOPMENT AND INDUSTRIAL PHARMACY
卷 41, 期 7, 页码 1137-1147出版社
TAYLOR & FRANCIS LTD
DOI: 10.3109/03639045.2014.935390
关键词
alpha-tocopherol succinate; controlled drug release; paclitaxel; synergistic chemotherapy
The aim of this study was to develop chitosan derivative polymeric micelles for co-delivery of paclitaxel (PTX) and alpha-tocopherol succinate (alpha-TS) to the cancer cells to improve the therapeutic efficiency and reduce side effects of PTX. In this study, amphiphilic tocopheryl succinate-grafted chitosan oligosaccharide was synthesized and physically loaded by PTX and alpha-TS with entrapment efficiency of 67.9% and 73.2%, respectively. Physical incorporation of alpha-TS into the micelles increased the hydrophobic interaction between PTX and the micelles core, which improved micelle stability, reduced the micelle size and also sustained the PTX release from the micelles. The mean particle size and zeta potential of alpha TS/PTX-loaded micelles were about 133 nm and + 25.2 mV, respectively, and PTX release was completed during 6-9 d from the micelles. Furthermore, the cytotoxicity of alpha-TS/PTX-loaded micelles against human ovarian cancer cell line cancer cell in vitro was higher than that of PTX-loaded micelles and the free drug solution. Half maximal inhibitory concentration values of PTX after 48-h exposure of the cells to the PTX-loaded micelles modified and unmodified with alpha-TS were 110 and 188 ng/ml, respectively.
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