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

Cristina García-Mouton1, Mercedes Echaide1, Luis A Serrano2

  • 1Department of Biochemistry, Faculty of Biology, and Research Institute "Hospital 12 de Octubre (imas12)", Complutense University, 28040 Madrid, Spain.

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Summary

Pulmonary surfactant (PS) can deliver inhaled drugs. Novel research shows that three-dimensional liquid structures, not just interfacial layers, significantly enhance PS spreading and drug transport.

Keywords:
air–liquid interfaceinterfacial filminterfacial spreadingpulmonary drug deliverypulmonary surfactantsurface balancesurface-associated reservoir

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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.