Forsgren P, Modig J, Gerdin B, Axelsson B, Dahlbäck M
Department of Anesthesiology and Intensive Care, University Hospital, Uppsala, Sweden.
Ups J Med Sci. 1990;95(2):117-36. doi: 10.3109/03009739009178581.
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.
在早期成人呼吸窘迫综合征（ARDS）和其他炎症性肺部疾病中，肺部可能会受益于活性药物的高局部沉积，以便在无全身副作用的情况下优化局部浓度。在这项方法学研究中，我们使用了在控制通气下的猪。该研究分两步进行。在第一部分，将氯化钠中的伊文思蓝染料以雾化形式给药。在第二部分，以相同方式给药含氯化钠中异硫氰酸荧光素（FITC）标记脂质体的干粉。我们评估是否存在均匀、中央、外周和/或肺泡沉积，该操作是否可重复，以及是否与肺泡巨噬细胞存在相互作用。16只接受氯美噻唑麻醉和间歇正压通气（IPPV）的动物纳入研究。4只动物在雾化和基线测量后处死。5只动物作为对照接受静脉注射生理盐水。6只动物静脉注射内毒素（18微克·千克⁻¹·小时⁻¹）。1只动物在脂质体给药后15分钟和2小时进行支气管肺泡灌洗。在每个实验结束时，将肺充气、切除并在微波炉中干燥。以可重复的方式将每只动物的左肺切片，并分析不同区域的肺组织切片。提取肺组织中的伊文思蓝染料或磷脂部分（含脂质体），并进行荧光光谱分析。本研究表明，在可重复的条件下，能够给予雾化的伊文思蓝染料和脂质体，并在终末气道和/或肺泡腔中实现沉积。支气管肺泡灌洗显示脂质体与肺泡巨噬细胞存在相互作用。结果表明，携带活性药物并通过吸入给药的脂质体可用于早期ARDS和其他相关炎症性肺部疾病的局部肺部治疗。
