PDF(Pubmed)
Abstract：
Glipizide; an insulin secretagogue belonging to the sulfonylurea class, is a widely used antidiabetic drug for managing type 2 diabetes. However, the need for life-long administration and repeated doses poses challenges in maintaining optimal blood glucose levels. In this regard, orally active sustained-release nano-formulations can be a better alternative to traditional antidiabetic formulations. The present study explored an innovative approach by formulating orally active sustained-release nano-micelles using the amphiphilic lauric acid-conjugated-F127 (LAF127) block copolymer. LAF127 block copolymer was synthesized through esterification and thoroughly characterized before being employed to develop glipizide-loaded nano-micelles (GNM) via the thin-film hydration technique. The optimized formulation exhibited mean particle size of 341.40 ± 3.21 nm and depicted homogeneous particle size distribution with a polydispersity index (PDI) < 0.2. The formulation revealed a surface charge of -17.11 ± 6.23 mV. The in vitro release studies of glipizide from developed formulation depicted a sustained release profile. Drug loaded micelles exhibited a substantial reduction in blood glucose levels in diabetic rats for a duration of up to 24 h. Notably, neither the blank nano-micelles of LAF127 nor the drug loaded micelles manifested any indications of toxicity in healthy rats. This study provides an insight on suitability of synthesized LAF127 block copolymer for development of effective oral drug delivery systems for anti-diabetic activity without any significant adverse effects.
摘要：
格列吡嗪；一种属于磺酰脲类的胰岛素促分泌素，是一种广泛用于治疗2型糖尿病的抗糖尿病药物。然而,对终身给药和重复给药的需求对维持最佳血糖水平提出了挑战.在这方面,口服活性缓释纳米制剂可以更好地替代传统的抗糖尿病制剂。本研究探索了一种创新方法，通过使用两亲性月桂酸共轭F127（LAF127）嵌段共聚物配制口服活性缓释纳米胶束。LAF127嵌段共聚物通过酯化合成，并在通过薄膜水合技术用于开发格列吡嗪负载的纳米胶束（GNM）之前进行了彻底表征。优化的制剂表现出341.40±3.21nm的平均粒度,并且描绘了具有多分散指数(PDI)<0.2的均匀粒度分布。该制剂显示表面电荷为-17.11±6.23mV。格列吡嗪从开发的制剂的体外释放研究描绘了持续释放曲线。载药胶束在糖尿病大鼠中表现出血糖水平的大幅降低，持续时间长达24小时。值得注意的是，LAF127的空白纳米胶束和载药胶束在健康大鼠中均未表现出任何毒性迹象。这项研究提供了对合成的LAF127嵌段共聚物用于开发有效的口服给药系统的适用性的见解，该口服给药系统具有抗糖尿病活性，而没有任何明显的不良反应。
