Drug solubilization in lung surfactant

The relative affinity of glucocorticusteroids fut lung surfactant was deter mined for the purpose of identifying chemopreventive agents with a high the rapeutic index for lung cancer. The aqueous solubility and the extent of so lubilization in Survanta(TM), a native extract of bovine lung, of budesonid e, triamcinolone acetonide, dexamethasone, and flunisolide were determined as a function of temperature by a dialysis technique. The aqueous solubilit es at 37 degrees C were 19.6, 35.8, 103 and 120 mu g/ml for the above liste d compounds, respectively. The temperature dependence of the solubilities w as modest consistent with the hydrophobic properties of the steroids. The a mount of drug in solution was significantly enhanced in the presence of Sur vanta(TM) with solubilization ratios of 0.019, 0.023, 0.014, and 0.02 mu g drug dissolved per mu g of Survanta(TM) phospholipid. respectively. In addi tion, the extent of solubilization also generally increased with temperatur e, although the phase transition of the surfactant lipid appeared to compli cate the functional relation between temperature and solubilization. These results show that there is enhanced solubilization of glucocortosteroids by lung surfactant which is secreted by the cancer susceptible type II cells of the lung. (C) 2000 Elsevier Science B.V. All rights reserved.