环孢菌素A眼用纳米粒温敏凝胶的制备及质量评价

Preparation and quality evaluation of thermos-sensitive in situ gels containing cyclosporine A nanoparticles for ophthalmic use

目的优选环孢菌素A(cyclosporine A,CsA)眼用纳米粒温敏凝胶的处方,并考察其体外释药行为。方法采用纳米沉淀-高压均质法制备CsA纳米粒溶液。以泊洛沙姆407(poloxamer 407,F127)、泊洛沙姆188(poloxamer 188,P188)和壳聚糖的质量比为自变量、加泪液前和加泪液后的胶凝温度为因变量,用中心点复合设计响应面法构建投料比和胶凝温度的数学模型,并按照设定的目标胶凝温度筛选出F127、P188和壳聚糖的最优投料比。考察CsA眼用纳米粒凝胶的释药行为及机制。结果CsA纳米粒的粒径为220 nm,CsA眼用纳米粒温敏凝胶的最佳处方为F127、P188与壳聚糖的质量比为22.11∶1.75∶1.73,胶凝温度为(25.4±0.3)℃,用人工泪液稀释后的胶凝温度为(33.3±0.3)℃,24 h释药达90%。结论CsA眼用纳米粒温敏凝胶具有理想的胶凝温度和缓释作用,具有进一步开发的潜力。

Objective To optimize the formulation of thermo-sensitive in situ gels containing cyclosporine A(CsA)nanoparticles for ophthalmic use and to investigate their release properties in vitro.Methods CsA nanoparticles were prepared by nano-precipitation and high-pressure homogenization method.By taking the mass fraction of poloxamer 407,poloxamer 188 and chitosan as independent variables and the gelling temperature before and after adding tears as dependent variables,the relationship of feed ratio and gelling temperature were constructed by central point composite design response surface method,and the optimal feed ratio of poloxamer 407,poloxamer 188 and chitosan was selected according to the set target gelling temperature.The release behavior and mechanism of the gels were investigated.Results The diameter of the CsA nanoparticles was 220 nm.The optimal mass percentage of the gels was poloxamer 407∶poloxamer 188∶chitosan=22.11∶1.75∶1.73;The gelling temperature was(25.4±0.3)℃,and the gelling temperature after artificial tear dilution was(33.3±0.3)℃.The drug release was 90%in 24 hours.Conclusion Thermo-sensitive in situ gels containing CsA nanoparticles has the ideal gel temperature and slow release effect,and has the potential for further development.