星点设计-效应面法优化红细胞膜包裹藤黄酸仿生纳米粒处方工艺及其体外释放研究

Optimization of the formulation of bionic gambogic acid nanoparticles coated with erythrocyte membrane by central design-response surface method and its drug release in vitro

目的:以红细胞膜为载体制备藤黄酸仿生纳米粒(GPP@RBC-NPs),并考察其体外释放特性。方法:采用薄膜分散法制备GPP@RBC-NPs的中间产物GPP-NPs,以粒径、多分散指数(PDI)和包封率为评价指标,星点设计-效应面法优选GPP-NPs的制备工艺,再通过挤出法用RBCm包裹,得到GPP@RBC-NPs,对最优处方工艺制备的GPP@RBC-NPs进行理化性质和体外释放特性的考察。结果:GPP@RBC-NPs最佳工艺条件为:药载比为1:10;生理盐水与PEG3400-PLA2000用量的比为1.7:10(mL:mg);探头超声时间和功率分别为10min和10%;RBC膜的稀释倍数及破碎时间分别为4倍和3 min。GPP@RBC-NPs平均粒径为(94.10±1.67)nm,Zeta电位为(-6.96±0.60)mV,包封率为(79.11±1.42)%。透射电镜扫描结果表明,GPP@RBC-NPs呈粒径均匀的球形。稳定性结果表明,GPP@RBC-NPs在4℃条件下,储存稳定性良好。体外释放结果表明,72 h内GPP@RBC-NPs累计释放量30.35%,能明显延长GA的释放时间。结论:GPP@RBCNPs制备工艺简单,可重复性较好,明显改善了GA的溶解性和体外释放性能。

Objective:To prepare gambogic acid bionic nanoparticles(GPP@RBC-NPs)using erythrocyte membrane as carrier and to investigate its release characteristics in vitro.Method:The intermediate product GPP-NPS of GPP@RBC-NPs was prepared by thin-film dispersion method.The particle size,polydispersion index(PDI)and encapsulation rate were used as evaluation indexes.The preparation process of GPP-NPS was optimized by central design-response surface method.RBCm was used to coat the product by extruding,and GPP@RBC-NPs were obtained.The physicochemical properties and in vitro release characteristics of GPP@RBC-NPs prepared by the optimal formulation process were investigated.Result:The optimal technological conditions of GPP@RBC-NPs were drug loading ratio of 1:10.The dosage ratio of normal saline to PEG3400-PLA2000 was 1.7:10(mL:mg).The ultrasonic time and power of the probe were 10 min and 10%,respectively.The dilution ratio and crushing time of RBCm were 4 times and 3 min,respectively.The average particle size of GPP@RBC-NPs was(94.10±1.67)nm.The Zeta potential was(-6.96±0.60)mV,and the encapsulation rate was(79.11±1.42)%.The scanning results of transmission electron microscope showed that GPP@RBC-NPs were spherical with uniform particle size.The stability results showed that GPP@RBC-NPs had good storage stability at 4℃.The results of in vitro release showed that the cumulative release amount of GPP@RBC-NPs was 30.35%within 72 h,which could significantly prolong the release time of GA.Conclusion:The preparation process of GPP@RBC-NPs is simple and reproducible,and the solubility and in vitro release properties of GA are improved obviously.