壳聚糖/丹参酮ⅡA ph敏感微球的制备工艺及体外释药特性研究

RESEARCH ON THE PREPARATION TECHNOLOGY OF CHITOSAN/TANSHINONE ⅡA pH SENSITIVE MICROSPHERES AND ITS RELEASE CHARACTERISTICS IN VITRO

喷雾干燥法制备壳聚糖/丹参酮ⅡA微球并进行工艺优化,考察其体外释放特性。以壳聚糖为载体,通过喷雾干燥技术制备壳聚糖/丹参酮ⅡA微球,以壳聚糖浓度、丹参酮ⅡA浓度、混合时间为自变量,包封率和载药量为响应值,通过星点设计-效应面法优化制备工艺,采用傅立叶变换红外光谱(FT-IR),X-射线衍射(XRD),扫描电子显微镜(SEM)表征微球材料学性能;并考察微球体外释药规律及释药机理。结果表明,壳聚糖/丹参酮ⅡA微球的最佳制备工艺为壳聚糖0.9 wt%,丹参酮ⅡA 1 g·L^-1,混合时间21 min。微球的包封率为86.6%±0.7%,载药量为4.6%±0.06%;采用最优工艺制备的微球在pH1.2和pH7.4的环境下具有不同的释药特性,显示出一定的pH敏感性。制备工艺条件稳定可行,具有较高的包封率和载药量,释药性能良好,具有明显的pH敏感性,有望制备成丹参酮ⅡA的药物传递系统。

In order to optimize the preparation process of chitosan/tanshinone ⅡA microspheres,and evaluate its release performance in vitro,the spray drying technology was used.The microspheres were prepared through spray drying technology by using chitosan as the carrier.The Box-Benhnken design and response surface method was utilized to optimize the preparation procedures,by taking the concentration of chitosan and tanshinone ⅡA,and mixing time as independent variables,encapsulation efficiency and drug loading as response values.The Fourier transform infrared spectroscopy(FT-IR),X-ray diffraction(XRD),and scanning electron microscope(SEM) technologies were used to characterize the material properties of the microspheres;and the in vitro drug release rule and mechanism of the microspheres were investigated.Results showed that the optimized preparation process of chitosan/tanshinone ⅡA microspheres was obtained with chitosan concentration of 0.9 wt%,tanshinone ⅡA concentration of 1 g·L-1,and mixing time of 21 minutes. The encapsulation rate of the microspheres was 86.6%±0.7%,and the drug loading was 4.6%±0.06%.The microspheres prepared by the optimal process showed different drug release characteristics under two environments with the pH values of 1.2 and 7.4,indicating a good pH sensitivity.It could be concluded that the optimized preparation process was stable and feasible,with a high encapsulation efficiency and drug loading capacity,good drug release performance,and well pH sensitivity,implying to be expected to be prepared as a drug delivery system of tanshinone ⅡA.