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目的:制备紫杉醇mPEG-PLA共聚物胶束(PM-PTX),优化处方及工艺。方法:采用薄膜水化法制备PM-PTX,通过星点设计一效应面优化法设计和优化处方工艺,并评估药物的体外释放。结果:以投药量和水化体积作为自变量,包封率和载药量作为因变量,行多元线性回归及二次多项式拟合,优选最佳处方工艺并进行验证,得最优工艺条件为投药量2.71 mg,水化体积7.04 mL。按照优化处方制得的PM-PTX包封率为(83.04±1.96)%,载药量为(15.01±0.28)%,与预测值的偏差分别为1.91%和0.99%。PM-PTX溶液为无色透明,透射电镜下显示胶束呈类圆形,胶束粒径为(87.74±2.3)nm,多分散指数为0.259±0.014,Zeta电位为(-1.22±0.133)mV。在3种pH环境下,胶束的药物释放速率无明显差异(P>0.05),96 h的累积释放率分别为(92.19±3.17)%,(88.37±5.62)%和(86.04±2.16)%(pH=5.8,7.2,7.4)。结论:星点设计-效应面优化法对PM-PTX的制备工艺优化有效,所建立的模型预测性良好。
Objective: To prepare paclitaxel mPEG-PLA copolymer micelles (PM-PTX), optimize the prescription and process. Methods: PM-PTX was prepared by the membrane hydration method. The design and optimization of the formulation process were optimized by the star design-effect surface optimization method and the in vitro drug release was evaluated. Results: Taking the dosage of drug and hydration volume as the independent variable, the entrapment efficiency and drug loading as the dependent variables, the multiple linear regression and the quadratic polynomial fitting were performed. The optimal prescription was optimized and verified. The optimum technological conditions were Dosing 2.71 mg, hydration volume 7.04 mL. The encapsulation efficiency of PM-PTX was (83.04 ± 1.96)% and the drug loading was (15.01 ± 0.28)%. The deviation from the predicted value was 1.91% and 0.99%, respectively. The PM-PTX solution was colorless and transparent. The size of micelles was (87.74 ± 2.3) nm, the polydispersity index was 0.259 ± 0.014 and the zeta potential was (-1.22 ± 0.133) mV . Under the three pH conditions, the drug release rate of micelles was not significantly different (P> 0.05), and the cumulative release rates at 96 h were (92.19 ± 3.17)%, (88.37 ± 5.62)% and (86.04 ± 2.16)%, (pH = 5.8, 7.2, 7.4). Conclusion: The method of star-point design-response surface optimization is effective to optimize the preparation process of PM-PTX. The model established is of good predictability.