Solute Absorption from the Airways of the Isolated Rat Lung. II. Effect of Surfactants on Absorption of Fluorescein

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Abstract
To determine the effects on the pulmonary barrier of several surface active agents, a series of metered dose inhalers (MDIs) was prepared and used to dose aerosolized surfactant to the airways of isolated perfused rat lungs. The MDIs contained a range of concentrations, from 0.1 to 5.0% (w/w), of either oleic acid, oleyl alcohol, or Span 85, which released ≈45 µg (0.1%, w/w) to ≈1660 µg (5.0%, w/w) of surfactant per actuation. The permeability of the pulmonary barrier was assessed by the rate of transfer of disodium fluorescein dosed as 100 µl of aqueous solution (1 mg/ml) after administering the surfactants. Some 12.1 ± 4.7% of the recovered surfactant, per dose, was assessed to reach the pulmonary regions of the lung. All surfactants tested caused an increase in fluorescein transfer rates. A single actuation from the MDI containing 5% (w/w) oleic acid produced gross edema in all lungs tested within 40 min and the first-order half-lives of absorption were reduced almost threefold, from 12.9 ± 2.5 min for controls to 4.5 ± 0.8 min. Differences in absorption were noted between the acid and the alcohol, which is consistent with the hypothesis that both the hydrocarbon chain and the polar head group have roles in the altered permeability to fluorescein. The absorption of fluorescein when dosed from the MDI containing 5% (w/w) Span 85 was increased but all surfactants dosed from the lowest concentration MDI of 0.1% (w/w) did not alter absorption rates of the dye relative to those of controls. Results are discussed in light of current interest in absorption enhancement and the presence of surfactants in currently marketed MDIs.