Characterization and preparation of core-shell type nanoparticle for encapsulation of anticancer drug

摘要

The aim of this study is to prepare delivery vehicles of paclitaxel using low molecular weight water-soluble chitosan (LMWSC) and evaluate them as an anticancer drug delivery system. LMWSC was modified with methoxy polyethylene glycol (LMWSC-MPEG, ChitoPEG), and then it was conjugated with cholesterol (LMWSC-MPEG-Chol). Core-shell type LMWSC-MPEG-Chol nanoparticles (LMWSC-NPs) were prepared by the dialysis method, and the core-shell structure was confirmed by ~1H NMR analysis. To this polymer, paclitaxel was encapsulated and core-shell type nanoparticles were prepared. The release tests indicated that release of paclitaxel from the core-shell type nanoparticles and its transport across the dialysis membrane was slower than dialysis of free paclitaxel. In a cytotoxicity study using CT26 cell, the paclitaxel-encapsulated core-shell type nanoparticles (LMWSC-NPs) showed a toxicity against tumor cells similar to paclitaxel itself. The results of a tumor inhibition test with CT26 implanted upon mouse tumor models in vivo indicated that the application of a dose of 10mg/kg of LMWSC-NPT showed a superior survival rate, and a slower tumor growth than when paclitaxel alone was administered, although the tumor growth and survival rate were not significantly changed at a dose of 2mg/kg. The LMWSC-NPT dose above 10mg/kg showed a superior antitumor activity.