Preparation And Evaluation Of A Novel Chitosan Derivative As Hepatocyte-targeted Gene Carrier

Chitosan is a polysaccharide composed of D-glucosamine and N-acetyl-D-glucosamine. It can be mainly obtained by deacetylating chitin. It has been reported that chitosan has a potential for DNA complexation and thus, it has been selected as a non-viral vector for gene delivery. Since positive charge enhanced chitosan derivative would possibly has a higher gene transfer efficiency than chitosan itself, we already performed some investigations on combining glycidyl trimethylammonium chloride (GTMAC) with chitosan to achieve a novel chiosan derivative- N-[(2-hydroxy-3-trimethylammonium)propyl]chitosan (HTCC). In addition, lactobionic acid bearing galactose groups was also coupled with HTCC for hepatocyte specificity, and the degree of substitution of galactose could be reached as high as to 30 %. Successful grafting of the side chains was confirmed by FT-IR, 1H NMR and TG. characterizations. There was no obvious cytotoxicity detected in vitro when an amount of so produced new chiosan derivative below 50μg/mL was empolyed. On the basis of the obtained results, the product with a stronger positive-charge density and higher DS of galactose as well as lower cytotoxicity might serve as a potential gene-vector with an improved efficiency.