星点设计-效应面法优化去甲斑蝥素壳聚糖-丝素蛋白栓塞微球的制备  

Central composite design optimizes preparation of norcantharidin-loaded chitosan-fibroin microspheres for embolization

作　　者：张光宇[1] 迟美玉[1] 倪静[1] 陈袁兰[1] 宋玉玲[1] 王晓青[1] 张学农[1] 

机构地区：[1]苏州大学药学院药剂学教研室,苏州215123

出　　处：《中国新药杂志》2011年第17期1624-1630,共7页Chinese Journal of New Drugs

基　　金：国家"重大新药创制"科技重大专项(2009ZX09310-001);国家科技支撑计划(2006BAI09B00);国家科技型中小企业技术创新基金(07C26223201333)

摘　　要：目的:制备去甲斑蝥素壳聚糖-丝素蛋白栓塞微球(Norcantharidin-loaded chitosan-fibroin micro-spheres for embolization,NCTD-CS-SF-MS),考察其包封率,载药量及外观形态,并对其体外释放特性进行考察。方法:采用乳化-交联固化法制备NCTD-CS-SF-MS,其中以液体石蜡为油相,壳聚糖(chitosan CS)与丝素蛋白(silk fibroin SF)的物理混合溶液为水相,Span-80为乳化剂,戊二醛为交联剂。星点设计-效应面法优化制备工艺,扫描电镜观察微球表面形态及X-射线衍射(XRD)、差示量热扫描(DSC)表征微球特性。采用体外动态透析法测定微球在不同介质条件下的释药性能。结果:制备的微球形态圆整,大小均匀,平均粒径约(184±5)μm,载药量(15.08±2.85)%,包封率(27.46±1.25)%。微球在0.1 mol.L-1 HCl、PBS(pH=7.4)和生理盐水中的释放均遵循Weibull方程。结论:所优化的制备工艺简单易行,缓释作用显著。Objective： To develop a preparation technique, and to determine the envelop efficiency, drug loading and the surface morphology of the norcantharidin-loaded chitosan-fibroin microspheres （NCTD-CS-SF-MS） , and the release dynamics of NCTD-CS-SF-MS in vitro by dynamic dialysis system. Methods： NCTD-CS-SF-MS were achieved by emulsification cross-linking process with liquid paraffin as oil phase. The hybrid of chitosan （CS） and silk fibroin （SF） was used as water phase, Span-80 as emulsifier, and glutaraldehyde as cross linking agent. The central composite design was applied to optimize the formulation and preparation procedure. The surface mor- phology of the microspheres was observed by scanning electron microscopy （SEM） , the interaction of the drug and the polymer was analyzed by XRD and DSC. Dynamic dialysis method was used to determine the release characteristie of norcantharidin from microspheres in vitro. Results： The microspheres with a global shape and narrow size distribution were prepared. Its average diameter was （184 ± 5）μm, the drug loading and the envelop efficiency of microspheres were （15.08 ±2.85）% and （27.46 ± 1.25）%, respectively. All the drug release behaviors at 0.1mol·L^-1 HCl, phosphate buffered saline （pH = 7.4） and saline followed Weibull distribution model. Conclusion： The optimized preparation technique is feasible, by which NCTD-CS-SF-MS with evident effect of sustained drug release are prepared.

关 键 词：去甲斑蝥素 壳聚糖.丝素蛋白 栓塞微球 制备 

分 类 号：R943.41[医药卫生—药剂学] R979.1[医药卫生—药学]