Synthesis And Characterization Of Amphiphilic Chitosan Bearing Hepatocyte-targeting Ligand

As a novel polymeric micellar material for hepatocyte-targeting, galactosylated acyl chitosan was synthesized. First, acyl chitosans was prepared by conjugating chitosan with hydrophobic fatty acyl group in methane sulfonic acid as solvent and catalyzer. Compared with chitosan, the solubility of the acyl chitoan (lauroyl chitosan and palmitoyl chitosan) in organic solvents was improved due to the destruction of compact crystal structure within chitosan. The critical micelle concentration (CMC) of the acyl chitosan was low. The structure of the acyl chitosan was characterized by FT-IR and ~1H-NMR, and the degree of substitution was calculated. The solubility of palmitoyl chitosan and lauroyl chitosan in chloroform was determined. The CMC of palmitoyl chitosan and lauroyl chitosan were determined by spectrofluorometric method using pyrene as fluorescent probe.Based on the acyl chitosan, galactosylated acyl chitosan was prepared by conjugating acyl chitosan with lactobionic acid using EDC as catalyzer. FT-IR and ~1H-NMR were used to characterize the structure of the galactosylated acyl chitosan. The CMC and solubility of the galactosylated acyl chitosan were determined. A series of galactosylated acyl chitosans with different molecules and degrees of substitution were prepared in order to investigate the relationships of molecule structure and CMC.The results showed that methane sulfonic acid was an effective solvent and catalyzer for the acyl reaction. The CMC and solubility of acyl chitosan were directly affected by the degree of substitution. With a low CMC, galactosylated acyl chitosan is a potential polymeric micelle material for hepatocyte-targeting.