表没食子儿茶素没食子酸酯壳聚糖纳米粒的制备及其药剂学性质研究

Preparation and characterization of epigallocatechin-3-gallate chitosan nanoparticles

目的制备表没食子儿茶素没食子酸酯(EGCG)壳聚糖(CS)纳米粒(EGCG-CS-NPs),并初步评价其理化性质。方法采用离子凝胶化法制备EGCG-CS-NPs,通过对处方优化:CS质量浓度(X_1)、三聚磷酸钠(TPP)质量浓度(X_2)、EGCG质量浓度(X_3)为考察对象,以包封率(Y_1,%)、平均粒径(Y_2,nm)为评价指标,利用Box-Behnken设计-效应面法优化EGCG-CS-NPs处方;采用Malvern粒度仪测定EGCG-CS-NPs的粒径分布和Zeta电位,透射电镜考察其形态;并考察EGCGCS-NPs的体外释药行为。结果 EGCG-CS-NPs的最优处方:CS质量浓度为2.6 g/L、TPP质量浓度为1.5 g/L、EGCG质量浓度为2.7 g/L,制备的EGCG-CS-NPs的包封率为(85.8±3.1)%;粒径为(102.2±27.1)nm,Zeta电位为(25.5±4.1)m V;透射电镜显示EGCG-CS-NPs粒径均一,呈球状;EGCG-CS-NPs在24 h内平稳缓慢释药(p H 4.5 PBS)。结论通过对处方的优化,制备得到圆整、释药缓慢的EGCG-CS-NPs,为进一步考察EGCG-CS-NPs在大鼠体内药效学奠定了基础。

Objective To prepare the epigallocatechin-3-gallate （EGCG） chitosan nanoparticles （CS-NPs） and investigate their physicochemical properties. Methods The EGCG-CS-NPs were prepared by ion gelation method. The formulation variables were optimized by Box-Behnken Design （BBD） of response surface methodology （RSM） of CS concentration （X0, sodium tripolyphosphate concentration （X2）, and EGCG concentration （X3） as independent variables and encapsulation efficiency （Y1, %） and particle size （Y2, nm） as dependent variables. The optimized CS-NPs were characterized for encapsulation efficiency （EE）, particle size, Zeta potential, morphology, and in vitro drug release behavior of EGCG-CS-NPs were studied. Results An optimal EGCG-CS-NPs consisting of CS concentration as 2.6 g/L, sodium tripolyphosphate concentration as 1.5 g/L and EGCG concentration as 2.7 g/L. For EE, particle size, Zeta potential of EGCG-CS-NPs were found to be （85.8 ±3.1）%, （102.2 ± 27.1） nm, and （25.5 ± 4.1） mV, respectively. The CS-NPs were found to be small and spherical as seen in transmission electron microscopy （TEM）. The in vitro release data proved that the drug release was steady within 24 h （pH 4.5 PBS）. Conclusion Through optimizing the formulation, we obtain the uniform EGCG-CS- NPs with in vitro sustained-release behavior. This work is useful for the further research on pharmacodynamics of EGCG-CS-NPs.