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Abstract
In this paper, a new drug delivery system was designed using magnetic Fe3O4/carboxymethylchitosan nanoparticles (Fe3O4/CMCS NPs) as carrier and rapamycin (Rapa) as the antitumor drug. The process and formulation variables of Fe3O4/CMCS-Rapa NPs were optimized using response surface methodology (RSM) with a three-level, three-factor Box-Behnken design (BBD). The independent variables were the mass ratio of Fe3O4/CMCS: Rapa, W/O phase ratio and stirring rate; dependent variables were drug loading content and entrapment efficiency. Mathematical equations and response surface plots were used to relate the dependent and independent variables. The optimized formulation was characterized by TEM, FT-IR, and in vitro drug release. Results for mean particle size, drug loading content, entrapment efficiency and in vitro drug release of Fe3O4/CMCS-Rapa were found to be of 30 ± 2 nm, 6.32% ± 3.36%, 62.9% ± 2.30%, and 65.35% ± 2.46% at pH 7.4 after 70 h, respectively; also, they possess magnetism with a saturation magnetization of 67.1 emu/g, negligible coercivity and remanence at room temperature. Also the effect of magnetic targeted nanoparticles on the proliferation of human hepatoma cell line HepG2 in vitro was investigated. The results from MTT assays showed that the Fe3O4/CMCS-Rapa nanoparticles could effectively inhibit the proliferation of HepG2 cells, which displayed time or concentration-dependent manner. All these results indicated that the nanoparticles had the potential to be used as a novel drug carrier system.
Acknowledgments
This work was supported by the Science Fund of Hunan Province Office of Education of China (No. 11 W004), the National Science Fund of Guangxi province of China (No. PF110259) and Science Fund of Guangxi Key Laboratory of Functional Phytochemicals Research and Utilization (No. FPRU2011-7).