基于耗散粒子动力学模拟辅助的纳米结构脂质载体优化制备

Optimized preparation of nanostructured lipid carriers based on dissipative particle dynamics simulation

基于分子模拟能够探究纳米结构脂质载体(nanostructure lipid carriers,NLC)各物质间的结合能、溶解度参数等,预测混合物的相容性,从而用于指导实验前原料种类以及用量选择。该文以姜黄素(curcumin,Cur)为模型营养物,以固体脂质(单硬脂酸甘油酯)和液体脂质(中链甘油三酯、葵花籽油、甜橙油)及表面活性剂(泊洛沙姆188、卵磷脂、吐温-80)作为筛选对象,采用耗散粒子动力学(dissipative particle dynamics,DPD)方法进行模拟筛选,再通过正交试验制备NLC以对模拟结果进行验证,最后对NLC的粒径和微观形态等进行表征。模拟与实验结果均表明,单硬脂酸甘油酯-中链甘油三酯(medium chain triglycerides,MCT)-卵磷脂能形成较好的载体体系,固液脂质比为1∶3(质量比),卵磷脂含量为5%(质量分数),姜黄素含量占总脂质的3%(质量分数)时形成的球壳结构最好。优化后制备的姜黄素NLC平均粒径为(233.8±2.4)nm,电位为(-38.2±0.6)mV,包封率为85.06%,微观形态均匀分散、没有明显聚集现象。

Molecular simulation can be used to investigate the binding energy and solubility parameters of nanostructured lipid carriers(NLC)and predict the compatibility of the mixture,to guide the selection of raw materials and dosage before the experiment.In this study,curcumin(Cur)was used as the model nutrient,solid lipids(glycerol monostearate),liquid lipids(medium-chain triglyceride,sunflower oil,and sweet orange oil),and surfactants(poloxam188,lecithin,and Tween-80)were selected as the screening objects.The method of dissipative particle dynamics(DPD)was used to simulate,then NLC was prepared and the simulation results were verified through orthogonal experiments,and then the NLC was characterized.Simulation and experimental results showed that the carrier system formed by triglyceride monostearate-medium chain triglycerides(MCT)-lecithin was better,and the best spherical shell structure was formed when the solid-liquid lipid ratio was 1:3,the lecithin content was 5%,and the curcumin content was 3%of the total lipid.The average particle size of the optimized curcumin NLC was(233.8±2.4)nm,the potential was(-38.2±0.6)mV,the encapsulation rate was 85.06%,and the micromorphology was uniformly dispersed without obvious aggregation.