响应面法优化PEG积雪草酸脂质纳米粒及促小肠吸收研究.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 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 ±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—醇亲水修饰;在体肠灌流 法; 聚乙—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 土0.9) mV, drug loading of (15. 4土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 po