title: In vitro and in vivo activities of leukotriene B4-loaded biodegradable microspheres.
abstract: Leukotriene B(4) (LTB(4)) is a potent inflammatory mediator and stimulates the immune response. In addition, LTB(4) 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 LTB(4)-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 LTB(4), using enzyme immunoassay and evaluated in vitro MS uptake by peritoneal macrophages. To assess the preservation of neutrophil chemoattractant activity, LTB(4)-loaded MS were tested in vitro (in a modified Boyden microchamber) and in vivo, after intratracheal administration.
authors.affiliation: Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Av. do Café s/n, 14040-903 Ribeirão Preto, Brazil.
authors.forename: Roberto
authors.initials: R
authors.lastname: Nicolete
authors.forename: Karla de Melo
authors.initials: Kde M
authors.lastname: Lima
authors.forename: José M R
authors.initials: JM
authors.lastname: Júnior
authors.forename: Marcelo D
authors.initials: MD
authors.lastname: Baruffi
authors.forename: Alexandra I
authors.initials: AI
authors.lastname: de Medeiros
authors.forename: Maria V L B
authors.initials: MV
authors.lastname: Bentley
authors.forename: Célio L
authors.initials: CL
authors.lastname: Silva
authors.forename: Lúcia H
authors.initials: LH
authors.lastname: Faccioli
mesh_terms: D000818:Animals; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D006016:Glycolates / Q000378:metabolism; D006801:Humans; D007249:Inflammation; D019344:Lactic Acid; D007975:Leukotriene B4 / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology; D017737:Macrophages, Peritoneal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008863:Microspheres; D008962:Models, Theoretical; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects; D010316:Particle Size; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000378:metabolism
chemical_list: D006016:Glycolates; D007975:Leukotriene B4; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid