Differential effects of cholesterol and budesonide on biophysical properties of clinical surfactant

INTRODUCTION: Corticosteroids have been widely used in clinical medicine as a first-line therapy to modify the inflammatory response in many pulmonary and systemic diseases. Inhaled and intratracheally administered corticosteroids have a particular interest in that their use allows the clinician to circumvent systemic steroid side effects. However, it is vital that corticosteroids delivered via the lungs not interfere with surface activity of the pulmonary surfactant lining layer. RESULTS: We found differential effects of cholesterol and budesonide on the biophysical properties of a cholesterol-free clinical surfactant preparation, Curosurf. At a low concentration up to 1%, both steroids play a similar role of fluidizing the surfactant film. However, when steroid concentration is increased to 10%, cholesterol induces a unique phase transition that abolishes the surface activity of the Curosurf film. By contrast, 10% budesonide simply fluidizes the film, thus having only limited effects on surface activity. DISCUSSION: Together with those of a previous study using a cholesterol-containing surfactant, our findings suggest that cholesterol-free surfactant preparations may be more advantageous than cholesterol-containing preparations as a carrier of budesonide because a larger amount of the drug may be delivered to the lungs without significantly compromising the surface activity of pulmonary surfactant. METHODS: Langmuir balance was used to study the effect of cholesterol and budesonide added at different concentrations on surface activity of Curosurf. Atomic force microscopy (AFM) was used to reveal their effects on the interfacial molecular organization and lateral structure of Curosurf films.