Uchida T, Nagareya N, Sakakibara S, Konishi Y, Nakai A, Nishikata M, Matsuyama K, Yoshida K
Faculty of Pharmaceutical Sciences, Mukogawa Women's University, Nishinomiya City, Japan.
Chem Pharm Bull (Tokyo). 1997 Sep;45(9):1539-43. doi: 10.1248/cpb.45.1539.
The objective of this study was to produce polylactic acid (PLA) microspheres containing bovine insulin as a sparingly water soluble model drug using a water-in-oil-in-water (w/o/w) emulsion solvent evaporation method. The preparative conditions were optimized. Employment of smaller internal aqueous phase volume (50 microliters or 100 microliters) in the manufacturing process, resulted in the high loading efficiency (over 95% of theoretical insulin loading efficiency). The addition of 10% (w/v) NaCl to the external aqueous phase (0.5% polyvinyl alcohol solution) reduced loading efficiency compared to the case where no NaCl was added to the external phase. The mean volume diameter for prepared PLA microspheres was in the region of 15-25 microns in all cases. PLA microspheres containing 5% and 10% insulin theoretically exhibited burst release in the initial stage. After a three week dissolution test, the surface of the microspheres became more porous due to the degradable characteristics of PLA polymer itself. Nevertheless, about 80% of the insulin still remained undegraded in PLA microspheres. Finally, insulin-loaded PLA microspheres (corresponding to 4 I.U. insulin) were administered to normal rats subcutaneously, and the pharmacological effect (a decrease in serum glucose level) was demonstrated.
本研究的目的是采用水包油包水（w/o/w）乳液溶剂蒸发法制备含有牛胰岛素作为难溶性模型药物的聚乳酸（PLA）微球。对制备条件进行了优化。在制造过程中采用较小的内水相体积（50微升或100微升），可实现较高的载药效率（超过理论胰岛素载药效率的95%）。与在外水相中不添加氯化钠的情况相比，在外水相（0.5%聚乙烯醇溶液）中添加10%（w/v）氯化钠会降低载药效率。在所有情况下，制备的PLA微球的平均体积直径在15 - 25微米范围内。理论上，含有5%和10%胰岛素的PLA微球在初始阶段表现出突释现象。经过三周的溶出试验后，由于PLA聚合物本身的可降解特性，微球表面变得更加多孔。然而，约80%的胰岛素仍未在PLA微球中降解。最后，将载有胰岛素的PLA微球（相当于4国际单位胰岛素）皮下注射给正常大鼠，并证明了其药理作用（血清葡萄糖水平降低）。
