异补骨脂素纳米结构脂质载体的制备及其体外透皮研究.docVIP

异补骨脂素纳米结构脂质载体的制备及其体外透皮研究 　　[摘要] 为增加异补骨脂素的皮肤透过量及滞留量，提高其生物利用度。该文采用高压均质法制备异补骨脂素纳米结构脂质载体（IPRN-NLC），以包封率、载药量及平均粒径为评价指标，运用正交实验优化最佳处方。采用Franze扩散池法考察IPRN-NLC的体外透皮。结果表明，最优处方固液脂质比为7∶3，药脂比1∶30，表面活性剂1%，制备的IPRN-NLC平均包封率为（90.25±0.73）%，平均载药量为（1.56±0.27）%，平均粒径为（305±1.57） nm；体外透皮实验显示IPRN-NLC提高了IPRN的皮肤透过量，且皮肤滞留量是IPRN（水）溶液的3倍。采用高压均质法制备的IPRN-NLC提高了IPRN的皮肤透过量及滞留量，在经皮给药领域具有广阔的应用前景。 　　[关键词] 异补骨脂素；纳米结构脂质载体；体外透皮；皮肤滞留量 　　[Abstract] To increase the permeation and retention of isopsoralen in skin， and improve its bioavailability.Isopsoralen loaded nanostructure liquid carrier （IPRN-NLC） was prepared by high pressure homogenization andoptimized by orthogonal experiment with the encapsulation efficiency， drug loading and average particle size as the evaluation indexes. The in vitro transdermal permeation of IPRN-NLC was evaluated by Franze diffusion cells.The results showed that solid-liquid lipid ratio of optimum IPRN-NLC formulation was 7∶3，drug-lipid ratio of 1∶30， 1% surfactant. Under these conditions， IPRN-NLC had an average encapsulation of （90.25±0.73）%，drug loading of （1.56±0.27）% and an average particle size of （305±1.57） nm.The in vitro transdermal permeation results showed that IPRN-NLC could increase the amount of IPRN permeated though skin， with 3 times of the epidermal retention as compared with IPRN solution. From the results we can know that the IPRN-NLC prepared by high pressure homogenization can improve the permeation andaccumulation of IPRN in the skin， with wide application prospects in the field of transdermal administration. 　　[Key words] isopsoralen；nanostructured lipid carrier；in vitro transdermal permeation；skin retention 　　白癜?L是由皮肤和毛囊处的黑素细胞内酪氨酸酶的功能减退、丧失所引起的一种常见的色素障碍性皮肤疾病[1]。黑色素合成减少是白癜风发病的直接原因，而酪氨酸酶是皮肤黑素生物合成的关键酶，因此提高酪氨酸酶的活性是治疗白癜风的关键[2]。补骨脂为豆科植物补骨脂Psoralea corylifolia L.的干燥成熟果实，可用于治疗白癜风、斑秃、牛皮癣以及瘤样皮肤病[3-5]。补骨脂中香豆素类成分异补骨脂素（isopsoralen，IPRN）具有光敏性，可以提高酪氨酸酶的活性，促进黑色素合成，是治疗白癜风的主要药效成分[6]。然而，IPRN为难溶性物质，不易透皮且在皮肤表皮层滞留量少，生物利用度低，严重制约了其在皮肤领域的应用。 　　纳米结构脂质载体（nanostructured lipid