Prostaglandin E(2)-loaded microspheres as strategy to inhibit phagocytosis and modulate inflammatory mediators release

PGE(2), 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, PGE(2) is mainly produced by APCs and it can suppress the Th1-mediated immune responses. The aim of this study was to develop PGE(2)-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 PGE(2), using enzyme immunoassay and MS uptake by peritoneal macrophages. To assess the preservation of biological activities of this mediator, we determined the effect of PGE(2) released from MS on LPS-induced TNF-alpha release by murine peritoneal macrophages. We also analyzed the effect of encapsulated PGE(2) on inflammatory mediators release from HUVECs. Finally, we studied the effect of PGE(2) 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. (C) 2008 Elsevier B.V. All rights reserved.

FAPESP Fundacao de Amparo a Pesquisa do Estado de Sao Paulo[02/12856-2]

FAPESP Fundacao de Amparo a Pesquisa do Estado de Sao Paulo[05/00110-4]

CNPq Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPp)[SAF 2005-01649]

CICYT

Spanish Ministerio de Educacion y Ciencia

Carlos III Health Institute[CB06/06/0027]

Spanish Ministry of Health

Conselleria de Cultura y Educacion (Generalitat Valenciana)

Programa de Mobilidade Internacional, Banco Santander

University of Valencia, Spain