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

Prostaglandins Other Lipid Mediat. 2007 Feb;83(1-2):121-9. doi: 10.1016/j.prostaglandins.2006.10.007. Epub 2006 Dec 1.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chemotaxis, Leukocyte / drug effects
  • Glycolates / metabolism
  • Humans
  • Inflammation
  • Lactic Acid
  • Leukotriene B4 / administration & dosage
  • Leukotriene B4 / metabolism*
  • Leukotriene B4 / pharmacology
  • Macrophages, Peritoneal / cytology
  • Macrophages, Peritoneal / drug effects
  • Macrophages, Peritoneal / metabolism
  • Male
  • Mice
  • Microspheres*
  • Models, Theoretical
  • Neutrophils / cytology
  • Neutrophils / drug effects
  • Particle Size
  • Polyglycolic Acid
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Pulmonary Alveoli / drug effects
  • Pulmonary Alveoli / metabolism

Substances

  • Glycolates
  • Leukotriene B4
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polyglycolic Acid
  • Lactic Acid