Study On Preparation And Application Of Chitosan-calcium Alginate Composite Microspheres

Chitosan is one of the most abundant natural polymers on the world. Its chemical structure gives it inherent natural properties such as hemostasis, antibacterial, biodegradation, cell compatibility, and non-toxic. In addition, it is the only naturally-occurring cationic polysaccharide polymer; Its chains in solution have high positive charge density. Chitosan forms polyelectrolyte complexes with water soluble anionic polymer under mild physiological conditions.Sodium alginate (SA) is a natural polysaccharide carbohydrate extracted from brown seaweed. It is a biodegradable polymer with stability, solubility, viscosity and safety for biomedical materials. It can form complexes with calcium ions, chitosan, and poly lysine. In this paper, chitosan and SA were used as raw materials to make porous chitosan/SA microspheres (CAMS) through emulsion and thermally induced phase separation (TIPS) method. Core-shell composite microspheres (CS@AlgCa-MS) consisted of shell of calcium alginate, and core of chitosan porous microspheres, were also prepared. The main results and conclusions were listed below.(1) CAMS was prepared by the emulsion method in combination with TIPS. Its hemostatic properties were studied. Firstly, the optimal preparation conditions for CAMS were explored. The CAMS particles were white powder. Their size was in a range of 70-110 um. The surface of CAMS had lots of pores with size less than 1.5 ?m. CAMS was analyzed by IR spectrum, XPS and cross-sectional SEM, The CAMS was confirmed to be a core (chitosan)-shell (calcium alginate) composite microsphere. Secondly, the hemostatic properties including the dynamics of in vitro procoagulant activity, hemostatic test on rat liver wound hemostatic, and whole blood clotting kinetics of CAMS were studied. Meanwhile, hemostatic agent tranexamic acid (TA) was loaded into CAMS (CAMS-TA) to improve CAMS's hemostatic properties. It was found that CAMS and CAMS-TA were superior to Celox in both hemostasis time and bleeding amount. The histological study showed that CAMS would not cause secondary damage to the tissue surrounding the wounds. The hemostatic mechanism of CAMS and CAMS-TA was also discussed.(2) The preparation of porous shell-core composite microspheres CS@AlgCa-MS, where the porous chitosan microspheres were used as core, while calcium alginate was as a dense shell layer. CS@AlgCa-MS was used as a carrier for the loading and sustaining-release of two model drugs (doxorubicin hydrochloride, DOX). Compared to CSMS, CS@AlgCa-MS could prevent the burst release of DOX, extend the releasing time, and show obvious sustained-release effect. In order to make full use of the shell (calcium alginate), which is a characteristic pH responsive material, BSA was loaded into CS@AlgCa-MS. It showed that CS@AlgCa-MS could resist the dissolution of BSA in gastric acid, so that BSA could reach and release in the colon site. CS@AlgCa-MS is suitable for loading protein drugs that are beneficial to be absorbed in the colon.