Interfacial Organization and Structural Changes in Model Lung Surfactants Induced by Methylxanthines

Area of Science:

• Biophysics
• Materials Science
• Pharmacology

Background:

• Methylxanthines like theophylline are used for COPD and asthma but have limitations.
• Localized inhalation delivery could improve therapeutic windows and reduce toxicity.

Purpose of the Study:

• Investigate the physicochemical interactions between theophylline, theophylline-7-acetic acid, and model pulmonary surfactants.
• Assess the feasibility of localized inhalation delivery for these drugs.

Main Methods:

• Studied drug effects on 2D lipid monolayers (DPPC, DPPG, mixture) at the air-water interface.
• Utilized Brewster angle microscopy (BAM), GIXD, and PM-IRRAS for structural analysis.
• Confirmed findings in 3D using giant unilamellar vesicles (GUVs) and fluorescence microscopy.

Main Results:

• Theophylline-7-acetic acid significantly disrupted lipid organization and altered surface properties.
• Drug-induced changes in molecular packing (rectangular to hexagonal) and head group interactions were observed.
• Evidence of drug-induced phase separation and morphological changes in GUVs.

Conclusions:

• Theophylline-7-acetic acid has a more pronounced effect on lung surfactant models than theophylline, likely due to electrostatic interactions.
• Findings provide insights into methylxanthine-lung surfactant interactions and pulmonary interface stability under drug exposure.
• Supports understanding for optimizing localized inhalation delivery strategies.