Study On Liver-targeting Galactosylated Palmitoyl Chitosan Polymeric Micelles As Drug Carriers

As a new drug carrier, polymeric micelles have potential application in nano drug delivery system, because of its unique core-shell structure and properties. In this paper, a hepatocyte-targeting amphiphilic chitosan derivative, galactosylated palmitoyl chitosan, was used as carrier material to prepare polymeric micelles, and its properties and in vitro anti-tumor activity were investigated.Galactosylated palmitoyl chitosans with different degree of substitution of alkyl prepared by our research group were used as carrier material. Polymeric micelles were prepared by emulsifying-solvent evaporation technique. The critical micelle concentrations (CMC) of polymeric micelles were determined by fluorescence spectrophotometry, using pyrene as a hydrophobic probe. Galactosylated palmitoyl chitosan with appropriate CMC was selected as the carrier material for preparing drug-loaded polymeric micelles. Using Hydroxyl camptothecin (HCPT) as model drug and chloroform-methanol mixed solvent as the dissolving medium (also as oil phase) of drug and carrier material, the drug-loaded polymeric micelles were prepared by emulsifying-solvent evaporation technique. The encapsulation efficiency (EE) and drug loading (DL) was determined by ultraviolet spectrophotometry. On the basis of single factor experiments, orthogonal design test was used to optimize the formulation and process. The optimal formulation and process was as follows: the ratio of drug and carrier material was 0.2 to 1, the ratio of oil phase and water phase was 1 to 7, and the ultrasound time was 40 minutes. The morphology of drug-loaded polymeric micelles was characterized by transmission electron microscopy (TEM). The particle size and zeta potential were determined by Zetasizer Nano-ZS90. The in vitro release of HCPT from polymeric micelles were determined in 0.1 mol/L phosphate buffer solutions (PBS, pH=7.4) containing 0.02% Tween 80, and its sustained-release mechanism was analyzed. The in vitro effects of drug-loaded polymeric micelles on proliferation of HepG2 cells were investigated by MTT assay, and compared with HCPT solution and blank polymeric micelles. The inhibition effect of drug-loaded polymeric micelles on HepG2 cells was lower than HCPT solution, and blank micelles had little inhibition effect on HepG2 cells.