Controlled Release of Glucocorticoid via PLGA Nanoparticles for Modulating Macrophage Polarization in Inflammation Situations

Abstract

Glucocorticoids are among the most widely used anti-inflammatory and immunosuppressive drugs. However, their prolonged administration is associated with a wide range of adverse side effects including long-lasting immunosuppression. In this study, we aimed to encapsulate two commonly used glucocorticoids with different potency and duration, hydrocortisone and dexamethasone, into poly(lactic-co-glycolic acid) (PLGA) nanoparticles with the goal to enhance their therapeutic efficacy and safety profile. We evaluated their anti-inflammatory properties in two in vitro models varying the timing of treatment administration based on lipopolysaccharide M1-polarized macrophages, key effectors of the innate immune system. Our results demonstrated that, for both strategies, drug-loaded nanoparticles significantly reduced the expression of interleukin-6, a pro-inflammatory cytokine, more effectively than the free drugs. However, in one of the strategies, while free drugs induced upregulation of interleukin-10, a key anti-inflammatory cytokine, no such effect was observed with the nanoparticle-based formulations. These findings suggest that encapsulating glucocorticoids into PLGA may provide a more controlled and selective modulation of the inflammatory response, potentially reducing the risk of excessive immunosuppression. Overall, our study highlights the potential of PLGA nanoparticles as nanocarrier to improve glucocorticoid efficiency by promoting a more balanced modulation of macrophage polarization in inflammation responses.