Nicolete Roberto, Lima Karla de Melo, Júnior José M R, Baruffi Marcelo D, de Medeiros Alexandra I, Bentley Maria V L B, Silva Célio L, Faccioli Lúcia H
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.
Prostaglandins Other Lipid Mediat. 2007 Feb;83(1-2):121-9. doi: 10.1016/j.prostaglandins.2006.10.007. Epub 2006 Dec 1.
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.
白三烯B(4)（LTB(4)）是一种强效的炎症介质，可刺激免疫反应。此外，LTB(4)可促进白细胞功能，如多形核白细胞的吞噬作用、趋化作用和化学运动，还可调节细胞因子的释放。然而，白三烯的一些物理化学特性，如水溶性差和化学不稳定性，使其难以在体内给药。本研究的目的是开发负载LTB(4)的微球（MS），以延长和维持该介质在体内的释放。选择水包油乳液溶剂萃取-蒸发法制备脂质负载的MS。我们测定了它们的直径，使用酶免疫测定法评估了LTB(4)的体外释放，并评估了腹膜巨噬细胞对MS的体外摄取。为了评估中性粒细胞趋化活性的保留情况，在气管内给药后，对负载LTB(4)的MS进行了体外（在改良的博伊登微室中）和体内测试。
