Norcantharidin-associated galactosylated chitosan nanoparticles for hepatocyte-targeted delivery

In this study a new chitosan (CS) derivative, galactosylated chitosan (GC), was synthesized and used to prepare norcantharidin-associated GC nanoparticles (NCTD-GC NPs) by taking advantage of the ionic cross-linkage between the molecules of the anti-hepatocarcinoma medicine NCTD and of the GC as carrier. NCTD-GC NPs were obtained with average particle size of 118.68 ± 3.37 nm, entrapment efficiency of 57.92 ± 0.40%, and drug-loading amount of 10.38 ± 0.06%. Several important factors influencing the entrapment efficiency, drug-loading amount, and particle size of NCTD-GC NPs were studied. The characteristics of sustained and pH-sensitive release of NCTD from NCTD-GC NPs in vitro were studied. In addition, in vitro cellular uptake and cytotoxicity of nanoparticles to hepatoma cell lines SMMC-7721 and HepG2 were also investigated. In vitro, and compared to CS-based NCTD-CS NPs, NCTD-GC NPs demonstrated satisfactory compatibility with hepatoma cells and strong cytotoxicity against hepatocellular carcinoma cells. In vivo antitumor activity of NCTD-GC NPs was evaluated in mice bearing H22 liver tumors. NCTD-GC NPs displayed tumor inhibition effect in mice, better than either the free NCTD or the NCTD-CS NPs. As a hepatocyte-targeting carrier, GC NPs are potentially promising for clinical applications. In this paper, a galactosylated chitosan (GC), was synthesized and norcantharidin (NCTD)-associated galactosylated chitosan nanoparticles (NCTDGC NPs) were generated by coupling NCTD - an anti-hepatocarcinoma drug - and GC as carrier. Compared to chitosan nanoparticles, NCTD-GC-NPs demonstrated satisfactory compatibility with hepatoma cells and strong cytotoxicity against the cells.