Surfactant versus saline as a vehicle for corticosteroid delivery to the lungs of ventilated rabbits

Abstract

Local administration of steroids to the lungs in ventilated newborn infants can minimize the harmful side effects that occur with systemic administration. An efficient system of drug delivery that provides uniform distribution within the lungs is essential for the treatment of bronchopulmonary dysplasia. In this study we compare surfactant with 0.9% saline solution as vehicles for the direct instillation of a steroid (budesonide) into the lungs. Twenty-two anesthetized, ventilated rabbits received [3H]budesonide in either 0.9% saline or surfactant, administered through an endotracheal tube. Before drug administration, bronchial lavage was performed on half of the animals to serve as a model for surfactant deficiency. Lung samples were analyzed by both autoradiography (alveolar versus airway distribution) and liquid scintillation counting (central versus peripheral deposition). As expected, the delivered concentration of [3H]budesonide decreased as airway size decreased and branching increased. Significantly less [3H]budesonide was deposited in the alveolar spaces of all study groups compared with that deposited in the small and large airways (p < 0.05). However, both vehicles were equally efficient in delivering [3H]budenoside, to the lungs. Although the alveolar and peripheral areas received less (4-11%) of the drug than the central tissue (14-28%), this was consistent among all the groups and was not affected by altered lung compliance. Therefore, either surfactant or saline could be sued to efficiently and reliably deliver budenoside to the lungs at a level greater than reported using nebulizers. Because normal saline is currently used for tracheal toilette it is likely to be preferred considering the increased costs associated with surfactant.