Abstract

PEGylated stealth nanoparticles have emerged as promising drug delivery carrier for cancer therapy. In this study, natural polycationic chitosan was grafted with poly(ethylene glycol) (PEG) to improve the water-solubility and long-circulation. Then PEGylated chitosan nanoparticles were formed by electrostatic interaction between sulfonic acid group of anionic functional polymer and protic amino group of PEGylated chitosan, using polyelectrolyte complex method. Effects of various factors on particle size and distribution, and the stability, biocompatibility, long-circulation ability were investigated. The results showed that when the concentration of PEGylated chitosan and anionic polymer was 0.20 mg/mL, pH of PEGylated chitosan was 5.0, pH of polymer was 5.5 and molar ratio (S/N) was 0.83, particle size of the prepared nanoparticles was 261.2 ± 5.5 nm with pdI of 0.070. Nanoparticles were relatively stable for more than 4 days under pH < 7.0 and normal saline conditions. The results of cytotoxicity experiments showed that the toxicity of PEGylated chitosan nanoparticles was greatly reduced, which met the basic requirements of biomedical materials. The cellular uptake efficiency of PEGylated chitosan nanoparticles was about 4 times lower than that of conventional chitosan nanoparticles, which indicated long circulation time of PEGylated chitosan nanoparticles in the blood. It was expected that this kind of stealth nanoparticles would have a broad application prospect in the field of drug delivery system.

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