In vitro and in vivo activities of leukotriene B4-loaded biodegradable microspheres

Leukotriene B4 (LTB4) is a potent inflammatory mediator and stimulates the immune response. In addition, LTB4 promotes leukocyte functions such as phagocytosis, chemotaxis and chemokinesis of polymorphonuclear leukocytes, as well as modulates cytokine release. However, some physicochemical characteristics of leukotrienes, such as poor solubility in water and chemical instability, make them difficult to administer in vivo. The aim of this study was to develop LTB4-loaded microspheres (MS) that prolong and sustain the in vivo release of this mediator. An oil-in-water emulsion solvent extraction–evaporation method was chosen to prepare the lipid-loaded MS. We determined their diameters, evaluated the in vitro release of LTB4, using enzyme immunoassay and evaluated in vitro MS uptake by peritoneal macrophages. To assess the preservation of neutrophil chemoattractant activity, LTB4-loaded MS were tested in vitro (in a modified Boyden microchamber) and in vivo, after intratracheal administration.