Drug solubilization in lung surfactant.
The relative affinity of glucocorticosteroids for lung surfactant was determined for the purpose of identifying chemopreventive agents with a high therapeutic index for lung cancer. The aqueous solubility and the extent of solubilization in Survanta, a native extract of bovine lung, of budesonide, triamcinolone acetonide, dexamethasone, and flunisolide were determined as a function of temperature by a dialysis technique. The aqueous solubilites at 37 degrees C were 19.6, 35.8, 104 and 120 microg/ml for the above listed compounds, respectively. The temperature dependence of the solubilities was modest consistent with the hydrophobic properties of the steroids. The amount of drug in solution was significantly enhanced in the presence of Survanta with solubilization ratios of 0. 019, 0.023, 0.014, and 0.02 microg drug dissolved per microg of Survanta phospholipid, respectively. In addition, the extent of solubilization also generally increased with temperature, although the phase transition of the surfactant lipid appeared to complicate 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.
Wiedmann
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Department of Pharmaceutics, University of Minnesota, 308 Harvard St. SE, Minneapolis, MN 55455, USA. weidm001@tc.umn.edu
Bhatia
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Wattenberg
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D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use; D002417:Cattle; D005938:Glucocorticoids / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D011650:Pulmonary Alveoli / Q000166:cytology / Q000378:metabolism; D011663:Pulmonary Surfactants / Q000737:chemistry*; D012995:Solubility; D013056:Spectrophotometry, Ultraviolet; D013816:Thermodynamics
D018931:Antineoplastic Agents, Hormonal; D005938:Glucocorticoids; D004364:Pharmaceutical Preparations; D011663:Pulmonary Surfactants