Polymyxin B-Enriched Exogenous Lung Surfactant: Thermodynamics and Structure

Area of Science:

• Biophysics
• Materials Science
• Pharmacology

Background:

• Exogenous pulmonary surfactants (EPS) are promising for drug delivery to the lungs.
• Polymyxin B (PxB) is an antibiotic with potential for combined therapy when delivered via EPS.
• Understanding PxB interaction with EPS is crucial for optimizing drug delivery strategies.

Purpose of the Study:

• To evaluate the interaction between polymyxin B (PxB) and poractant alfa Curosurf (PSUR), a clinically used EPS.
• To compare PxB interaction with PSUR and a protein-free model system (MS) to understand composition-specific effects.
• To determine the impact of PxB binding on the structural and physical properties of PSUR.

Main Methods:

• Differential scanning calorimetry (DSC)
• Small- and wide-angle X-ray scattering (SAXS/WAXS)
• Small-angle neutron scattering (SANS)
• Fluorescence spectroscopy
• Electrophoretic light scattering (ELS)

Main Results:

• Electrostatic interactions dominate PxB binding to EPS, with PxB localizing on the PSUR bilayer surface.
• PxB binding strengthens the multilamellar structure of PSUR and negligibly affects lipid bilayer thickness.
• PxB does not alter PSUR's gel-to-fluid phase transition temperature, but increases it in the protein-free MS.

Conclusions:

• The study supports the concept of combined therapy using PxB-enriched Curosurf for lung drug delivery.
• PxB's hydrophobic tail does not penetrate the lipid bilayer, and its binding strengthens the surfactant structure.
• Careful assessment of PxB concentration ( < 5 wt %) is recommended to prevent surface charge inversion.