Semaglutide sustained-release microspheres with single-phase zero-order release behavior: Effects of polymer blending and surfactants

Semaglutide has the advantages of high efficacy and fewer side effects in the treatment of Type 2 diabetes (T2DM). However, the marketed formulations of semaglutide have issues such as poor compliance in individuals who require repeated injections and low oral bioavailability, limiting its use. To overcome the aforementioned issues, semaglutide microspheres with single-phase zero-order release behavior were created using two methods: polymer blending and surfactant addition. Their characteristics, in vitro release, and in vivo pharmacodynamics were investigated. Two types of semaglutide microspheres show a desirable encapsulation effectiveness and smaller particle size. When compared to ordinary semaglutide microspheres (SEM-MS), due to the introduction of hydrophilic substances such as low molecular weight PLGA and Tween 20, the lag phase disappears, it exhibits zero-order release, with better in vitro release behavior. When injected subcutaneously to T2DM rats, the drug was continuously released for about a month, and the blood drug concentration fluctuated little, exhibiting good hypoglycemic and repair β cell effects. The efficacy is superior to SEM-MS and consistent with injection. The semaglutide microspheres created by two ways in this investigation can address the issues with commercial formulations while remaining safe.