Description
Pulmonary surfactant (PS) is a complex proteolipid system whose biophysical function relies on a delicate balance between membrane structure, phase behavior, and interfacial properties. The incorporation of small amphiphilic or lipophilic molecules into surfactant membranes can modify lipid packing and alter their thermodynamic characteristics. Budesonide (BUD), a widely used inhaled corticosteroid, represents an interesting model compound for studying drug–membrane interactions due to its pronounced lipophilicity. We investigated the partitioning of BUD into a model bilayer of pulmonary surfactant composed of a complex lipid mixture dipalmitoylphosphatidylcholine : palmitoyloleoylphosphatidylcholine : palmitoyllinoleoylphosphatidylcholine : palmitoyloleoylphosphatidylglycerol (DPPC : POPC : PLPC : POPG = 50 : 24 : 16 : 10 wt%). Densitometric and differential scanning calorimetry (DSC) measurements were performed in the 10–50 °C temperature range to determine the apparent molecular volume of BUD and its effect on the thermodynamic parameters of the gel-to-fluid phase transition of the PS model.
Our results revealed two distinct incorporation regimes separated by a breakpoint at ~2 wt% BUD. Below this concentration, the apparent molecular volume of BUD in the membrane was negative, indicating a strong influence of BUD on lipid packing. Simultaneously, the volume expansivity coefficient increased relative to the pure PS model, the main gel-to-fluid transition shifted to lower temperatures, and the transition enthalpy increased. Above 2 wt% BUD, all parameters approached nearly constant values, with the apparent molecular volume reaching the value of crystalline BUD. These findings suggest preferential accommodation of BUD within the hydrophobic core of the bilayer at low concentrations. The observed breakpoint indicates saturation of this incorporation mode, with altered BUD localization within the bilayer.
Experiments were supported by VEGA 1/0305/24 project.