Development of 1 Month Sustained-Release Microspheres Containing Liraglutide for Type 2 Diabetes Treatment

作者：Zejing Gao, Wei Yi, Jia Ge, Jingxuan Liu, Ying Qin, Fangling Gong, Guanghui Ma · 发表于：ACS Applied Materials & Interfaces · 年份：2024 · DOI：10.1021/acsami.4c04010 · 被引用次数：11 · 研究领域：Diabetes Treatment and Management、Diabetes Management and Research、Pancreatic function and diabetes

Liraglutide has been extensively applied in the treatment of type 2 diabetes mellitus (T2DM), but its 11–15 h half-life resulted in daily administration, which led to poor patient compliance. This study aimed to solve this problem by developing liraglutide-loaded microspheres with a 1 month sustained release prepared by the W 1 /O/W 2 method combined with the premix membrane emulsification technique to improve therapeutic efficacy. Remarkably, we found that the amphiphilic properties of liraglutide successfully reduced the oil–water interfacial tension, resulting in a stable primary emulsion and decreasing the level of drug leakage into the external water phase. As a result, exceptional drug loading (>8%) and encapsulation efficiency (>85%) of microspheres were achieved. Furthermore, the uniformity in microsphere size facilitated an in-depth exploration of the structural characteristics of liraglutide-loaded microspheres. The results indicated that the dimensions of the internal cavities of the microspheres were significantly influenced by the size of the inner water droplets in the primary emulsion. A denser and more uniform cavity structure decreased the initial burst release, improving the release process of liraglutide from the microspheres. To evaluate the release behavior of liraglutide from microspheres, a set of in vitro release assays and in vivo pharmacodynamics were performed. The liraglutide-loaded microspheres effectively decreased fasting blood glucose (FBG) lev...