Lactose-based glycoconjugates with variable spacers for design of liver-targeted liposomes

Asialoglycoprotein receptors are highly abundant on the hepatocyte surface and have specific binding sites for blood serum glycoproteins. Such discovery resulted in development of liver-targeted drug delivery systems because modification of the liposomal surface by carbohydrate derivatives results in an increase of endocytosis, which facilitates selective uptake of such systems by hepatocytes. In this study we have synthesized novel lactose derivatives containing a palmitic hydrophobic domain. They were used for modification of the liposome surface. Transfection activity of modified liposomes was analyzed on the HepG2 cell line (hepatocytes) and showed an increase in the transfection efficiency as compared to the non-modified liposomes. At the same time transfection activities of modified and non-modified liposomes were similar in the case of a non-hepatocyte cell line (293T). The novel lactose-based glycoconjugates may be a promising tool for developing efficient vectors for delivery of nucleic acids to hepatocytes.