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.
Nicolete
Roberto
R
Departamento de Análises Clínicas, Universidade de São Paulo, Ribeirão Preto, Brazil.
Lima
Karla de Melo
Kde M
Júnior
José M R
JM
Jose
Peter J
PJ
Sanz
María-Jesús
MJ
Faccioli
Lúcia Helena
LH
D000818:Animals; D002478:Cells, Cultured; D002626:Chemistry, Pharmaceutical; D018932:Chemokine CCL2 / Q000378:metabolism; D003692:Delayed-Action Preparations; D015232:Dinoprostone / Q000737:chemistry / Q000494:pharmacology*; D004195:Disease Models, Animal; D004339:Drug Compounding; D004655:Emulsions; D042783:Endothelial Cells / Q000187:drug effects* / Q000276:immunology; D006801:Humans; D007155:Immunologic Factors / Q000737:chemistry / Q000494:pharmacology*; D018836:Inflammation Mediators / Q000378:metabolism*; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D008863:Microspheres; D009569:Nitric Oxide / Q000378:metabolism; D009821:Oils / Q000737:chemistry; D010316:Particle Size; D010587:Phagocytosis / Q000187:drug effects*; D018805:Sepsis / Q000276:immunology / Q000517:prevention & control; D012995:Solubility; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014867:Water / Q000737:chemistry
C111835:CCL2 protein, human; D018932:Chemokine CCL2; D003692:Delayed-Action Preparations; D004655:Emulsions; D007155:Immunologic Factors; D018836:Inflammation Mediators; D009821:Oils; D014409:Tumor Necrosis Factor-alpha; D014867:Water; D009569:Nitric Oxide; D015232:Dinoprostone