基于Brij97液晶的胰岛素皮下注射给药载体制备.docVIP

基于Brij97液晶的胰岛素皮下注射给药载体制备 　　[摘要] 目的 用非离子型表面活性剂聚氧乙烯（10）油基醚（Brij97）制备可供注射的胰岛素液晶载体，达到缓释药物的目的。 方法 通过调节Brij97-十四酸异丙酯（IPM）-水体系水分含量形成低黏度的层状相（L2）用于注射，利用偏光显微镜对体系的相转变行为进行研究。 结果 选择Brij97-IPM-水（18?U2?U3）（10%IPM）和Brij97-IPM-水（4?U1?U1）（20%IPM）作为载药体系，研究胰岛素从体系中释放的动力学。胰岛素液晶载体在1h内即可吸收水分形成黏度较高的六角相液晶，水分吸收符合二级动力学方程。 结论 两种体系都可以延缓药物的释放，但药物从Brij97 -IPM-水（4?U1?U1）体系中释放更加缓慢，说明随着油脂性添加物的增加缓释能力逐渐增强。Brij97 -IPM-水体系有望成为多肽类药物缓释给药载体。 　　[关键词] Brij97；液晶；胰岛素；皮下注射；缓释 　　[中图分类号] TQ467.32 [文献标识码] B [文章编号] 2095-0616（2014）04-64-04 　　Brij97 based liquid crystalline for sustained subcutaneous delivery of insulin 　　MA Aiming JIANG Shuguang HUANG Ling ZHOU Jianping 　　Department of Pharmaceutics， China Pharmaceutical University， Nanjing 210009， China 　　[Abstract] Objective To develop non-ionic surfactant polyoxyethylene （10） oleyl ether（Brij97）fluid precursor formulations for subcutaneous injection as a strategy to sustain the release of insulin. Methods To study the phase transition behavior of these formulations， different content of water was added， the resulting systems were characterized by polarized light microscopy. Results Two formulations containing Brij97-IPM-water （18?U2?U3）（w/w， referred to as 10%IPM） Brij97-IPM-water（4?U1?U1） （w/w， referred to as 20%IPM） were chosen to study insulin release kinetic. Fluid precursor formulations were transformed into hexagonal phases in one hour after contact with water. Water uptake followed second-order kinetics. Conclusion Drug release is prolonged by the precursor formulations， but the release from 20%IPM is significantly lower than 10%IPM after 24h， This indicate that capacity of sustained release increased with the increase of lipophilic additive. These results suggest the potential of BRIJ-based precursor formulations for sustained insulin release. 　　[Key words] Brij97； Liquid crystal； Insulin； Subcutaneous injection； Sustained release 　　溶致液晶（lyotropic liquid crystal）是两亲性分子溶解于溶剂后形成的有序的热力学稳定状态，由于液晶在药用载体领域的巨大潜力，近年来不断受到关注[1]。构成溶致液晶的主要有糖脂类、磷脂类和烷基甘油酯[2]，其中