81-LB: Novel Microsphere Technology Reducing Injection Site Reaction in the Development of Long-Acting GLP-1 RA Formulation

Microspheres are typically used for long-acting injectable formulation, but often the injection site reactions are reported as side effects. This can reduce patient compliance with medication despite the benefit of reducing the number of administrations. Side effects at the injection site are mostly derived from inflammatory reactions. Therefore, it is necessary to minimize inflammatory reactions for the successful development of long-acting diabetes treatments, including GLP-1 receptor agonists. The purpose of this study is to evaluate the injection site reaction in the placebo, semaglutide and tirzepatide microspheres manufactured using the conventional microsphere technology and to investigate the injection site reaction improvement in the placebo, semaglutide and tirzepatide microspheres manufactured using novel technology by adding anti-inflammatory agent, dexamethasone. Skin samples were collected from the injection site of SD rats on days 3 and 8 after the administration of microspheres with or without dexamethasone. The collected skin was stained with H&E to determine infiltration of inflammatory cells, angiogenesis, and fibrosis and was graded. When microspheres manufactured using the conventional method were subcutaneously administered to rats, infiltration of inflammatory cells and fibrous tissue formation occurred on both days 3 and 8. Higher dexamethasone content in the microsphere showed a tendency for the lesser occurrence of inflammation and greater anti-inflammatory effect in the test group. Surprisingly, improvement in the injection site reaction for microspheres containing dexamethasone was observed even at systemic dexamethasone concentrations much lower than the therapeutic level.

In conclusion, this novel microsphere containing a small amount of dexamethasone shows potential for the development of a long-acting GLP-1 microsphere injectable for diabetes treatment with reduced injection site reaction.