| Cyclosporin A (CsA) is a lipophilic cyclic polypeptide compounds with immuno-suppressive activity and has been widely used in organ transplantation. Narrow therapeutic window, high liver and kidney toxicity and low bioavailability of oral administration with a high variability limited its widespread use. Current clinical use nanoemulsion Neoral can form about30nm droplet to significantly improve CsA absorption. It still has severe renal toxicity and large amount of solubilizer CremophorRH40usage may have strong toxicity. For these deficiencies, biodegradable material PLA was used as carrier, non-toxic F68as the surfactant, improved solvent evaporation process to prepare CsA-PLA nano-carrier. Using response surface methodology to optimize and predict the preparation process of the CsA-PLA nano-carrier with entrapment efficiency, surface potential, mean particle size as indices. Its release behavior in vitro was studied to provide theoretical and practical basis for sustained and controlled release of CsA oral drug delivery.The single factor experiment was used with carrier particle size and entrapment efficiency as indices to investigate the impact of a variety of process conditions on the nano-carrier performance and the stability of the nanoparticles were discussed. Using response surface method with Quality by Design (QbD) concepts to optimize the preparation conditions of nanoparticles. CsA-PLA nanoparticles prepared under the optimum process were monodisperse, evenly rounded. The encapsulation efficiency was90.73%, very close to the predicted value91.05029%. It demonstrated the application potential of QbD in process optimization of CsA-PLA nanoparticles. Then in vitro release of the optimal nanoparticles was studied. Eight fitting models showed that the drug release in vitro was mainly dissolution release mechanism in the intestinal fluid, and diffusion release mechanism in the gastric juice. Drug release of alkaline medium was greater than acidic media. |
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