Synthesis of multifunctional chitosan with galactose as a targeting ligand for glycoprotein receptor

Abstract

Chitosan- O-PEG-galactose was synthesized through hydroxyl groups of chitosan, which followed several steps including protection of amino group of chitosan, pegylation of chitosan, galactosylation of pegylated chitosan, and final removal of protection to obtain chitosan- O-PEG-galactose. The synthesized intermediates and final product were characterized and confirmed by 1H NMR and FTIR, and the amounts of PEG and galactose conjugated with chitosan were measured. The pegylated chitosan possesses amphiphilic property in terms of soluble in both neutral aqueous (e.g., water) and organic solvents (e.g., DMF, dichloromethane). The corresponding critical micelle concentration is measured to be 0.56 mg/mL, and the size of micelles is 294.5 ± 2.3 nm with polydispersity 0.123 ± 0.021. The contents of PEG and galactose conjugated in chitosan- O-PEG-galactose are 98.09 ± 4.63% w/w and 3.06 ± 0.54% w/w, respectively. In terms of the degree of O-substitution of chitosan by PEG (DS PEG) and the degree of substitution of PEG by galactose (DS g) are 177.69% and 86.7%, respectively. Exclusively high DS PEG indicates both C6–OH and C3–OH of chitosan are conjugated with PEG polymer chains. Further prominent attachment of galactose onto hydroxyl end group of PEG allows chitosan- O-PEG-galactose to possess sufficient quantity of targeting moieties for asialoglycoprotein receptor on hepatocytes.