去甲斑蝥素壳聚糖-丝素蛋白栓塞微球的制备以及体外释放研究

目的:研究利用壳聚糖(chitosan,CS)和良好生物相容性的丝素蛋白(silk fibroin,SF)为载体,去甲斑蝥素(norcantharidin,NCTD)为模型药物,制备去甲斑蝥素壳聚糖-丝素蛋白微球(norcantharidin-chitosan-silk fibroin-microspheres,NCTD-CS-SF-MS)。并考察微球的载药量、包封率及微球表面形态以及微球的体外释放特性。方法:以液体石蜡为油相,壳聚糖与丝素蛋白的物理混合溶液为水相,Span-80为乳化剂,戊二醛为交联剂;采用乳化-交联固化法制备NCTD-CS-SF-MS。星点设计优化制备工艺,扫描电镜,观察微球表面形态及X-射线粉末衍射法(X-ray power diffraction,X-RD)和差示扫描量热法(differential scanning calorimetry,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NCTD-CS-SF-MS形态圆整,粒径分布较为均匀,平均粒径约(184.0±5.0)μm,载药量(15.08±2.85)%,包封率(27.46±1.25)%。NCTD-CS-SF-MS在0.1mol/L HCl,PBS(pH=7.4)和9.0mg/mL氯化钠溶液的3种介质中的释放均遵循Weibull方程。结论:优化的NCTD-CS-SF-MS制备工艺简单易行,载药量高,缓释作用良好。

Study on Preparation and Drug Release in vitro of Norcantharidin-chitosan-silk-fibroin Microspheres

Objective： To study the Norcantharidin-chitosan-silk fibroin microspheres （NCTD-CS-SF-MS） for transcatheter arterial chemoembolization（TACE） by using chitosan（CS）and silk fibroin（SF） as carriers and norcantharidin （NCTD） as model medicine,based on the excellent plasticity of CS and the biocompatibility of SF.To study the drug loading,envelop efficiency and the surface morphology of the microspheres,and to determine the release characteristic of norcantharidin from microspheres in vitro.Methods： NCTD-CS-SF-MS was carried out by emulsifying cross-linking process with liquid paraffin as oil phase,the hybrid of CS and SF 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 morphology of the microspheres was observed under scanning electron microscope （SEM）,the interaction of the drug and the polymer was analyzed by X-RD and DSC,and dynamic dialysismethod was used to determine the release characteristic of norcantharidin from microspheres in vitro.Results： Novel microsphere with a global shape and narrow distribution were prepared.The average diameter was about （184.0± 5.0） μm,the drug loading rate was （15.08±2.85）%,and the envelop efficiency of microspheres was （27.46±1.25）%.The drug release behavior at 0.1 mol/L HCl,phosphate buffered saline （pH =7.4） and physiological saline conformed Weibull distribution model.Conclusion： The optimized preparation technique was feasible,and microspheres with high drug-loading rate and evident effect of sustained drug release were prepared.