Barichello J M, Morishita M, Takayama K, Nagai T
Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Hoshi University, Ebara-2-4-41, Shinagawa-Ku, Tokyo 142-8501, Japan.
Int J Pharm. 1999 Jul 20;184(2):189-98. doi: 10.1016/s0378-5173(99)00119-2.
The main objective of this work was to evaluate the use of Pluronic (PF127) gels, polylactic-co-glycolic acid (PLGA) nanoparticles and their combination for parenteral delivery of peptides and proteins having short half-lives using insulin as a model drug. The in vitro insulin release profiles of various PF127 formulations were evaluated at 37 degrees C using a membraneless in vitro model. In vivo evaluation of the serum glucose and insulin levels was performed following subcutaneous administration of various insulin formulations in normal rats. The in vitro results demonstrated that the higher the concentration of PF127 in the gel, the slower the release of insulin from the matrices, independent of the vehicle used. The acute hypoglycemic peak resulting from administration of an insulin solution between 0.5 and 2.0 h after administration (peak at 1 h) is replaced after administration of insulin-PLGA nanoparticles by an almost constant hypoglycemic effect with a slower recovery of the serum glucose levels at about 2 h after administration. By loading insulin into PF127 gels, a slower and more prolonged hypoglycemic effect of insulin was obtained in inverse proportion to the polymer concentration. PF127 gel formulations containing insulin-PLGA nanoparticles had the most long-lasting hypoglycemic effects of all formulations. From the current in vitro and in vivo study, we concluded that PF127 gel formulations containing either drug or drug-nanoparticles could be useful for the preparation of a controlled delivery system for peptides and proteins having short half-lives.
本研究的主要目的是以胰岛素作为模型药物，评估普朗尼克（PF127）凝胶、聚乳酸-乙醇酸共聚物（PLGA）纳米粒及其组合用于肠胃外递送半衰期较短的肽和蛋白质的效果。使用无膜体外模型，在37℃下评估了各种PF127制剂的体外胰岛素释放曲线。在正常大鼠皮下注射各种胰岛素制剂后，对血清葡萄糖和胰岛素水平进行了体内评估。体外结果表明，凝胶中PF127的浓度越高，胰岛素从基质中的释放速度越慢，这与所使用的载体无关。胰岛素溶液给药后0.5至2.0小时（1小时达到峰值）出现的急性低血糖峰值，在注射胰岛素-PLGA纳米粒后，被几乎恒定的降糖作用所取代，给药后约2小时血清葡萄糖水平恢复较慢。通过将胰岛素负载到PF127凝胶中，胰岛素的降糖作用变得更缓慢、更持久，且与聚合物浓度成反比。含有胰岛素-PLGA纳米粒的PF127凝胶制剂在所有制剂中具有最持久的降糖作用。从目前的体外和体内研究中，我们得出结论，含有药物或药物-纳米粒的PF127凝胶制剂可用于制备半衰期较短的肽和蛋白质的控释系统。
