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

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 W1/O/W2 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) levels and hemoglobin A1c (HbA1c) levels while enhancing the pancreatic and hepatic functions in db/db mice. In conclusion, liraglutide sustained-release microspheres showed the potential for future clinical applications in the management of T2DM and provided an effective therapeutic approach to overcoming patient compliance issues.

A review of recent research and development on GLP-1 receptor agonists-sustained-release microspheres.

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are increasingly used in treating type 2 diabetes (T2D). However, owing to their limited oral bioavailability, most commercially available GLP-1 RAs are administered through frequent subcutaneous injections, which may result in poor patient compliance during clinical treatment. To improve patients' compliance, sustained-release GLP-1 RA-loaded microspheres have been explored. This review is an overview of recent progress and research in GLP-1 RA-loaded microspheres. First, the fabrication methods of GLP-1 RA-loaded microspheres including the coacervation method, emulsion-solvent evaporation method based on agitation, premix membrane emulsification technology, spray drying, microfluidic droplet technology, and supercritical fluid technology are summarized. Next, the strategies for maintaining GLP-1 RAs' stability and activity in microspheres by adding additives and PEGylation are reviewed. Finally, the effect of particle size, drug distribution, the internal structure of microspheres, and the hydrogel/microsphere composite strategy on improved release behavior is summarized.