Experimental Study Of Chitosan And Reacetylated Derivative Microspheres As Arterial Embolization Materials

Chitosan is obtained on an industrial scale by the alkaline deacetylation of chitin. It is a biodegradablely cationic polysaccharide with good physicochemical and biocompatible properties. It has been widely used in the field of artifical skin, drug delivery,artifical vessel, gene therapy and cancer therapy. In this paper, chitosan microspheres and its reacetylated derivative are successfully made. The preparation conditions and physicochemical properties of two microspheres have been studied, the biocompatibility and embolization efficacy to animals are investigated, which could provide some useful references for the futher in vivo clinical applications.Chitosan microspheres (CM) and reacetylated chitosan microspheres (ACM) are made by the methods of oil/water emulsification and acetic anhydride. Two microsphere samples have good dispersive, liquid, suspended properties by controlling some factors such as the proportion of water phase and oil phase; the emulsification time and glutaraldehyde cross-linking time; the speed of whisking. CM, ACM have the mean diameter of 80.79μm and 81.25μm. The results of potentiometric measurement and FTIR show the change of the main functional groups on the surface of microspheres. The encapsulation efficiency and drug loading percentage of ACM to Adriamycin hydrochloride (ADM) are 62.41%, 11.7%, the drug release curve of CM, ACM show a controlled release state in the experiment. ACM has some advantages in the drug loading and releasing.The cell compatibility is determined using the MTT method. The experiment result shows that the two blank microspheres have no toxicity to mice fibroblasts, which have a well state on fibroblast proliferation. With the increase in ADM concentration and extension of treatment, the IR % of ADM-loading microspheres suspension to all cells increased, and ADM-loading microspheres show better inhibition to cancer cells than ADM. The degree of deacetylation has an obviously influence in the cell adhesion capability of microspheres, cell adhesion on ACM surfaces show good growth condition. The protein adsorption of CM, ACM is affected by protein solution concentration and adsorption time, an accelerated mass adsorption is observed with the protein solution concentration increased for two particles. The hemolysis test result showed that ACM have less than 5% hemolysis in low and high microspheres solution concentrations. It indicated that ACM sample have well blood biocompatibility.In this paper, ACM is used to study biology behavior as embolization materials. The irritation of vein and muscle after injecting microspheres lixivium indicated that ACM cause less irritation. The in vivo performance to auricular arteries in rabbit results present here indicated that ACM could cause the arterial blood interruption, proliferation of endothelial cells and chickening of arterial walls. In conclusion, ACM has remarkable arterial embolization effects and is an excellent alternative to superselective embolization materials for end arteries.