星点设计–效应面法优化眼局部应用雷公藤红素纳米结构脂质载体处方

Preparation and Formulation Optimization of Loaded Celastrol Nanostructure Lipid Carriers for Topical Ocular Application

目的:采用星点设计–效应面法(CCD-RSM)优化应用于眼局部应用雷公藤红素纳米结构脂质载体(CEL-NLC)处方。方法: 通过测定雷公藤红素在各种脂质的溶解度,筛选出溶解度较好的脂质,采用微乳法制备CEL-NLC,分别以药物/脂质用量比(X1)、表面活性剂/助表面活性剂用量比(X2)为考察对象,以粒径(Y1)、包封率(Y2)和载药量(Y3)为考察指标,经效应面法预测最佳处方,并验证最佳处方。结果:根据CCD-RSM优化得出最佳处方为雷公藤红素40 mg,棕榈酸0.09 g,油酸0.18 g,吐温-80 4.34 g,甘油2.16 g。按最优处方制备的CEL-NLC包封率为(75.28 ±3.44)%,载药量为(0.45 ±0.02)%;粒径为(18.66 ±2.63) nm,多分散指数(PDI)为0.39 ±0.03。实际值与预测值偏差均小于5%。结论:采用CCD-RSM优化的CEL-NLC处方,包封率高,粒径小,稳定性好,方法可靠,可进一步用于眼局部应用雷公藤红素的后续研究。

Objective: The central composite design-response surface methodology (CCD-RSM) was used to optimize the application of tricorne nanostructured lipid carrier (CEL-NLC) in the local application of eyes. Methods: The lipid with the best solubility was screened out by determining the solubility of celastrol in different lipids. CEL-NLC was prepared by microemulsion technique. Quality of solid lipid (X1), quality of liquid lipid (X2), surfactant/cosurfactant (X3) as objects of investigation, while particle size (Y1), encapsulation efficiency (Y2) and drug loadings rate (Y3) as dependent variables, the optimal prescription was obtained by CCD-RSM and verified subsequently. Results: The best prescription of CEL-NLC was Celastrol 0.04 g, palmitic acid 0.09 g, oleic acid 0.18g, tween-80 4.34 g and Glycerine 2.16 g. The encapsulation efficiency was (75.28 ±3.44)%;the drug loading rate was (0.45 ±0.02)%;the particle size was (18.66 ±2.63) nm. The PDI was 0.39 ±0.03. The deviation between the measured and predicted values was less than 5%. Conclusion: The optimized CEL-NLC obtained by CCD-RSM has high encapsulation efficiency, small particle size and good stability, which can be further used in the follow-up study of local application of Celastrol in eyes.