响应面法优化PEG积雪草酸脂质纳米粒及促小肠吸收的研究.docVIP

响应面法优化PEG积雪草酸脂质纳米粒及促小肠吸收的研究 　　[摘要] 溶剂扩散法制备聚乙二醇修饰积雪草酸（asiatic acid，AA）纳米结构脂质载体（pegylated asiatic acid loaded nanostructured lipid carriers，p-AA-NLC），并结合星点设计-效应面法得到p-AA-NLC的最优处方工艺，其中PEG/脂质为8.0%，AA/脂质为22.0%，该条件下的纳米体系荷负电荷（-37.1±0.9） mV，粒径（111.2±2.9） nm，包封率大于90%，载药量适中（15.4±0.2）%。4个指标实验值与模型预测值相比偏差均小于5%，表明实验中建立的模型预测性良好。同时采用大鼠在体肠灌流模型对优化后的p-AA-NLC进行肠吸收考察，药物有效吸收系数（Peff）、吸收速率常数（Ka）等参数评价该亲水性修饰纳米粒的肠吸收情况，结果显示p-AA-NLC组的Peff，Ka较未修饰组有显著提高（P0.05），提示积雪草酸纳米结构脂质载体（asiatic acid loaded nanostructured lipid carriers，AA-NLC）经亲水性PEG修饰后其小肠吸收有明显的促进作用。 　　[关键词] 积雪草酸；纳米结构脂质载体；星点设计-效应面法；聚乙二醇亲水修饰；在体肠灌流 　　[Abstract] A solvent diffusion method was used to prepare pegylated asiatic acid （AA） loaded nanostructured lipid carriers （p-AA-NLC）. Then central composite design-response surface method was used to obtain optimum condition for preparation technology of p-AA-NLC， where PEG/lipid ratio was 8.0% and AA/lipid ratio was 22.0%. Under the optimum condition， the system had particle size of （111.2±2.9） nm， Zeta potential of （-37.1±0.9） mV， drug loading of （15.4±0.2）% and entrapment efficiency greater than 90%. The deviations between observed values and predicated values were all below 5%， indicating that the established model had a good predictability. Meanwhile， a low-speed single pass perfusion model of rat in situ was set up to estimate the absorption kinetics of p-AA-NLC in small intestine， where the effective permeability （Peff）， absorption rate constant （Ka） and other parameters were used to evaluate the drug absorption. It turned out that Peff and Ka in p-AA-NLC group were significantly higher than those in unmodified group （P0.05）， indicating that asiatic acid loaded nanostructured lipid carriers （AA-NLC） could enhance the effects on intestinal absorption after being modified with hydrophilic PEG. 　　[Key words] asiatic acid； nanostructured lipid carriers； central composite design-response surface method； hydrophilic modification with polyethylene glycol； intestinal perfusion in situ 　　doi：1