Introduction and Objective: Obesity is a major global health issue, yet current pharmacological options suffer from poor adherence. Injectable GLP-1 receptor agonists require frequent dosing, while conventional PLGA microspheres often show burst release at high drug loading. This study aimed to develop a long-acting semaglutide formulation, LEZ-001, for once-monthly dosing and compare its release profile with conventional microspheres. Methods: Semaglutide was nanoparticulated and encapsulated into PLGA microspheres via emulsion (LEZ-001). Formulations contained 15% or 25% drug loading. Controls used semaglutide directly dissolved and incorporated into PLGA microspheres (15%) without nanoparticle treatment. Microspheres were stored at 37 °C, sampled at intervals, and drug release quantified by HPLC. Results: Control microspheres released 50-60% within 72 h, showing a marked burst. LEZ-001 released only 5-10% at the same point, then gradually and consistently, exceeding 80% by day 28 without abrupt release. Higher nanoparticle proportion accelerated release but maintained burst-free kinetics. Conclusion: LEZ-001 achieved sustained, four-week release without initial burst, even at high loading. This strategy overcomes key limitations of conventional microspheres, enabling once-monthly dosing and potentially improving compliance. Clinical studies remain necessary to confirm efficacy and safety. Disclosure J. Cho: None.
JAEPYOUNG CHO (Fri,) studied this question.