Thermodynamic and Structural Study of Budesonide-Exogenous Lung Surfactant System

The clinical benefits of using exogenous pulmonary surfactant (EPS) as a carrier of budesonide (BUD), a non-halogenated corticosteroid with a broad anti-inflammatory effect, have been established. Using various experimental techniques (differential scanning calorimetry DSC, small- and wide- angle X-ray scattering SAXS/WAXS, small- angle neutron scattering SANS, fluorescence spectroscopy, dynamic light scattering DLS, and zeta potential), we investigated the effect of BUD on the thermodynamics and structure of the clinically used EPS, Curosurf((R)). We show that BUD facilitates the Curosurf((R)) phase transition from the gel to the fluid state, resulting in a decrease in the temperature of the main phase transition (Tm) and enthalpy (Delta H). The morphology of the Curosurf((R)) dispersion is maintained for BUD < 10 wt% of the Curosurf((R)) mass; BUD slightly increases the repeat distance d of the fluid lamellar phase in multilamellar vesicles (MLVs) resulting from the thickening of the lipid bilayer. The bilayer thickening (similar to 0.23 nm) was derived from SANS data. The presence of similar to 2 mmol/L of Ca2+ maintains the effect and structure of the MLVs. The changes in the lateral pressure of the Curosurf((R)) bilayer revealed that the intercalated BUD between the acyl chains of the surfactant's lipid molecules resides deeper in the hydrophobic region when its content exceeds similar to 6 wt%. Our studies support the concept of a combined therapy utilising budesonide-enriched Curosurf((R)).