Preparation Of Cyclosporine-loaded Chitosan/Alginate Microsphere And Its Properties Study

Drug-loaded microspheres can improve the bioavilability and extend the drug's action time, so in recent years it has been the hotpoint of new-model controlled-release preparation.Taking the natural polysaccharide-chitosan and sodium alginate as the main carrier material, the classical immunosuppressants-cyclosporine as the drug model, the mild and efficient Impulsine Electrostatic Technique as the preparation technology, the cyclosporine-loaded Chitosan/Algnate Microspheres are prepared. Its preparation process, membrane strength, and release in vitro are studied in detail. The microspheres have also been applied tentatively.Experimental results show that:1. The formula for making small microsphere has been studied. Adding surfactant in sodium alginate solution can reduce the surface tension of the solution and increase cyclosporine's solubility, which favor the preparation of small microsphere; Adding surfactant and NaCl in CaCl2 solution can reduce the surface tension of the solution which is helpful to keep microsphere's shape. It also confirmed that tween20, Hexadecyl trimethyl ammonium Bromide, NaCl will not affect the stability of cyclosporine in a short period of time.2. The optimum conditions to prepare cyclosporine-loaded Chitosan/Algnate Microspheres are as follows:1%(V/V) tween20,2g/L CsA,30g/L CaCl2,80g/L NaCl, 10g/L sodium alginate,0.1 g/L 1631. The conditions can not only ensure the small and uniform grading grain-size, but have good reliability and repeatability in guaranteeing high drug encapsulation ratio.3. In order to get the chitosan with higher DD, the paper studys the process of romoving the acetyl. the optimum conditions should be:flake chitosan,20min, the maximum power of 900W,50%(wt/v)NaOH.4. The effect of membrane formation conditions on the chitosan membrane strength in the simulated body fluid has been systimatically investigated.The microsphere stability has been improved adding the surfactant; As the increase of the molecular weight of chitosan and pH of chitosan solution, the membrane strength becomes weak first and strengthened then.When twenty thousand molecular weight, and pH=6.3, the best membrane strength is got. While the DD of chitosan increase, membrane strength is improved. When the DD is 94%, the stability is the best.5. The release process of the cyclosporine-loaded microspheres in the simulated body fluid is investigated.The whole release has four stages:burst release;low speed release; fast stable release and the last low speed release. Other than the framework erosion mechanism in the simulative intestine juice, in H2O and 0.9%NaCl the release mechanism is erosion-diffusion.6. The paper also study the tentative application in vivo. Drug-loaded microspheres prolong the residence time by adhering the intestinal wall.The conclusion that microsphere can extend the drug's action time is got from the cyclosporine concentration in blood. But we observed the Eye irritation after subconjunctival injection in rabbits, It still need further study.