Beyond the Interface: Improved Pulmonary Surfactant-Assisted Drug Delivery through Surface-Associated Structures

Area of Science:

• Biomedical Engineering
• Materials Science
• Pharmacology

Background:

• Pulmonary surfactant (PS) is a potential drug delivery system for inhaled therapies.
• Current research methods using interfacial paper bridges limit PS/drug transport studies to monomolecular layers.
• PS films are typically multi-layered, suggesting limitations in current in vitro models.

Purpose of the Study:

• To investigate the role of surface-associated structures in PS spreading and drug transport.
• To develop and utilize a novel vehiculization balance for studying 3D liquid layer transport.
• To compare drug and lipid transfer through interfacial bridges versus a fully open liquid layer.

Main Methods:

• Designed a novel vehiculization balance with donor and recipient compartments connected by a 3D liquid layer.
• Utilized various PS formulations and liposomes.
• Incorporated a fluorescent lipid dye and budesonide (BUD) as a model hydrophobic drug.

Main Results:

• The novel 3D liquid layer balance showed significantly greater transfer of lipids and BUD compared to the interfacial bridge method.
• Interfacial bridges restricted the transfer of lipids and drugs, unlike the open 3D liquid layer.
• Surface-associated 3D structures play a crucial role in PS spreading and drug delivery.

Conclusions:

• Three-dimensional structures connected to the PS interfacial film significantly contribute to interfacial drug delivery.
• The novel vehiculization balance provides a more accurate in vitro model for studying PS-mediated drug transport.
• These findings have implications for optimizing inhaled drug delivery systems using pulmonary surfactant.