Abstract
A water-insoluble anti-tumor agent, Paclitaxel (PTX) was successfully incorporated into polymeric micelles formed from new graft copolymers, N-octyl-N-(2-carboxyl-cyclohexamethenyl) chitosan derivatives(OCCC). The objective of this study was to optimize and characterize the novel PTX micelle (PTX-M). Furthermore, the pharmacokinetics, NIR-imaging, biodistribution, and anti-tumor effects of PTX-M were evaluated. The results showed that the PTX-M had high drug loading (43.25%). The Vd and t1/2β of PTX-M were increased by 11.4- and 2.83-fold, respectively, but the plasma AUC of PTX-M was 3.8-fold lower than that of Taxol. Biodistribution study indicated that PTX-M was widely distributed into most tissues, most of them found in liver, spleen, lung, and kidney. This result was similar with NIR(near-infrared)-imaging. Tumor growth was significantly inhibited after intravenous injection of PTX-M. PTX-M showed the enhanced anti-tumor effect and non-toxic effects compared with Taxol, the commercial product of PTX. Therefore, the chitosan-derived micelle system offered a stable and effective platform for cancer chemotherapy with PTX.
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