Thermodynamic and Structural Study of Budesonide-Exogenous Lung Surfactant System

Area of Science:

• Biophysics
• Materials Science
• Pharmacology

Background:

• Exogenous pulmonary surfactant (EPS) is clinically used as a carrier for budesonide (BUD), a potent anti-inflammatory corticosteroid.
• Understanding the interaction between BUD and EPS is crucial for optimizing drug delivery and therapeutic efficacy.

Purpose of the Study:

• To investigate the impact of budesonide (BUD) on the thermodynamic properties and structural organization of Curosurf®, a clinically utilized exogenous pulmonary surfactant (EPS).
• To elucidate the mechanism of BUD incorporation within the EPS structure and its influence on lipid bilayer behavior.

Main Methods:

• Differential scanning calorimetry (DSC) for thermodynamic analysis.
• X-ray scattering (SAXS/WAXS) and Small-angle neutron scattering (SANS) for structural characterization.
• Fluorescence spectroscopy, dynamic light scattering (DLS), and zeta potential measurements to assess dispersion properties.

Main Results:

• BUD facilitates the gel-to-fluid phase transition of Curosurf®, decreasing the main transition temperature (Tm) and enthalpy (ΔH).
• Curosurf® morphology is maintained for BUD content below 10 wt%, with increased lipid bilayer thickness observed.
• BUD intercalation within the lipid bilayer deepens into the hydrophobic region at higher concentrations (>6 wt%).

Conclusions:

• Budesonide (BUD) incorporation modifies the physical properties of Curosurf®, potentially enhancing its performance as a drug carrier.
• The findings support the development of budesonide-enriched Curosurf® for combined anti-inflammatory therapeutic strategies.
• Calcium ions (Ca2+) play a role in maintaining the structural integrity of budesonide-loaded surfactant vesicles.