Prostaglandin E2-loaded microspheres as strategy to inhibit phagocytosis and modulate inflammatory mediators release

PGE2, an arachidonic acid metabolite produced by various type of cells regulates a broad range of physiological activities in the endocrine, cardiovascular, gastrointestinal, and immune systems, and is involved in maintaining the local homeostasis. In the immune system, PGE2 is mainly produced by APCs and it can suppress the Th1-mediated immune responses. The aim of this study was to develop PGE2-loaded biodegradable MS that prolong and sustain the in vivo release of this mediator. An o/w emulsion solvent extraction–evaporation method was chosen to prepare the MS. We determined their diameters, evaluated the in vitro release of PGE2, using enzyme immunoassay and MS uptake by peritoneal macrophages. To assess the preservation of biological activities of this mediator, we determined the effect of PGE2 released from MS on LPS-induced TNF-α release by murine peritoneal macrophages. We also analyzed the effect of encapsulated PGE2 on inflammatory mediators release from HUVECs. Finally, we studied the effect of PGE2 released from biodegradable MS in sepsis animal model. The use of this formulation can provide an alternative strategy for treating infections, by modulating or inhibiting inflammatory responses, especially when they constitute an exacerbated profile.