伊曲康唑缓释微球的制备及体外抗真菌性能评价

Preparation and in vitro antifungal evaluation of itraconazole sustained release microspheres

目的以牛血清白蛋白(bovine serum albumin,BSA)和壳聚糖为载体制备伊曲康唑缓释微球(itraconazole sustained release microspheres,CS-BSA-ITZ),对其体外理化性质和抗真菌作用进行评价。方法首先,采用乳化化学交联法制备伊曲康唑白蛋白微球(itraconazole albumin microspheres,BSA-ITZ),利用Plackett Burman设计和Taguchi正交设计筛选出最佳制备.工艺,然后在其外层包覆壳聚糖以制备CS-BSA-ITZ,对微球的粒径、电位和体外累积释放率进行了表征,并测试了微球对白色念珠菌(C.albicans)的抗菌活性。结果制备的CS BSA-ITZ呈球形,包封率为(98.44±1.24)%,粒径为(4.20±0.26)μm,电位为(2.27±0.54)mV。体外释放结果显示,CS-BSA-ITZ可缓慢持续释放7 d。体外抗真菌结果表明,CS BSA-ITZ与游离伊曲康唑和BSA-ITZ相比,当药物质量浓度为1μg·mL^(-1)时,抑制率达99%,均高于游离伊曲康唑和BSA-ITZ。结论CS-BSA-ITZ具有明显的抗真菌效果,有望将其应用为抗真菌药物新制剂。

Objective To prepare itraconazole sustained release microspheres(CS-BSA-ITZ)using bovine serum albumin(BSA)and chitosan as carriers,and to evaluate its in vitro physicochemical properties and antifungal effects.M ethods Itraconazole albumin microspheres(BSA-ITZ)were first prepared by emulsification chemical cross-linking method,and the optimal preparation process was screened by Plackett-Burman design and Taguchi orthogonal design,then chitosan was coated on the outer layer to prepare CS-BSA-ITZ.The particle size,potential and in vitro cumulative release rates were characterized,and the antifungal activity of the microspheres against Candida albicans(C.albicans).Results CS-BSA-ITZ were spherical in shape with an encapsulation rate of(98.44±1.24)%,and the particle size and zeta potential were(4.20±0.26)μum and(2.27±0.54)mV.The in vitro release results showed that CS-BSA-ITZ could be released slowly and continuously for 7 d.The in vitro antifungal results showed that CS-BSA-ITZ showed 99%inhibition compared with free itraconazole and BSA-ITZ,both higher than free itraconazole and BSA-ITZ when the drug mass concentration was 1μg·mL^(-1).Conclusion CS-BSA-ITZ microspheres with obvious antifungal effects are expected to be applied as new antifungal drug preparations.