Comparison of Magnetically Responsive Trimethyl Chitosan and Chitosan Nanoparticles for Gemcitabine Delivery With in Vitro Studies

Abstract

Purpose: Gemcitabine is nucleoside analogue and used for various carcinomas like non-small cell lung cancer. Nanoparticle-based therapeutic agents have been developed for use in cancer therapy. Trimethyl chitosan TMC is methylated derivative of chitosan. TMC can be preferable because of the limited solubility of chitosan. Magnetic nanoparticles can be concentrated at cancerous tissue which provide targeted cancer therapy. In this study, we tried to develop and compare magnetically targeted trimethyl chitosan and chitosan nanoparticles for gemcitabine delivery in lung cancer therapy. Methods: Chitosan was trimethylated using methyl iodide. Magnetic nanoparticles were synthesized using co-precipitation method. TMC and chitosan nanoparticles were prepared by cross-linking method with tripolyphosphate. Gemcitabine was loaded onto nanoparticles via adsorption technique. After that characterization studies were performed and in vitro drug release tests were carried out. In order to determine cytotoxicites against A549-luc-C8 and CRL5809 cell lines, MTT assays were performed. Results and conclusion: Trimethylation of chitosan was verified with FTIR analysis. Gemcitabine was loaded with 54.7 and 30.3% on magnetic TMC nanoparticles and chitosan nanoparticles, respectively. According to drug release experiments, both carrier system had controlled drug release profile. IC50 values of gemcitabine loaded magnetic TMC nanoparticles were lower than that of magnetic chitosan nanoparticles. In conclusion, it was suggested that trimethyl chitosan nanoparticles had greater potential than chitosan nanoparticles for further analysis as a magnetically targeted therapy agent for lung cancer.

Keywords

• chitosan, trimethyl chitosan, gemcitabine, magnetic nanoparticle, drug delivery system, lung cancer

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