Intrapulmonary Deposition of Aerosolized Evans Blue Dye and Liposomes in an Experimental Porcine Model of Early Ards

Abstract

In early ARDS (Adult Respiratory Distress Syndrome) and other inflammatory pulmonary disorders the lung might benefit from a high local deposition of an active drug, in order to optimize the local concentration without systemic side effects. In this methodological study we used pigs under controlled ventilation. The study was carried out in two steps. In the first part Evans blue dye in NaCl was delivered in aerosolized form. In the second part a dry powder containing FITC (fluorescein-isothiocyanate)-labelled-liposomes in NaCl was delivered in the same way. We evaluated whether there was an even, central, peripheral and/or alveolar deposition, whether the procedure was reproducible, and whether there was an interaction with alveolar macrophages. Sixteen animals under chlormethiazole anaesthesia and intermittent positive pressure ventilation (IPPV) were included in the study. Four animals were sacrificed after nebulization and baseline measurements. Five animals served as controls and received saline i.v. Six animals received endotoxin i.v. (18 micrograms.kg-1.h-1). One animal underwent broncho-alveolar lavage 15 min and 2 h after liposome administration. At the end of each experiment the lungs were inflated with air, excised and dried in a microwave oven. The left lung of each animal was sliced in a reproducible manner and lung-pieces from different regions were analyzed. The Evans blue dye or the phospholipid fraction of the lungs (containing liposomes), was extracted and analyzed spectrofluorometrically. This study shows that it is possible, under reproducible conditions, to administer aerosolized Evans blue dye and liposomes and to achieve a deposition in the terminal airways and/or alveolar spaces. The broncho-alveolar lavage demonstrated an interaction of liposomes with alveolar macrophages. The results imply that liposomes carrying active drugs and administered by inhalation may be used for local pulmonary treatment in early ARDS and other related inflammatory pulmonary diseases.