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

Pulmonary surfactant (PS) has been proposed as an efficient drug delivery vehicle for inhaled therapies. Its ability to adsorb and spread interfacially and transport different drugs associated with it has been studied mainly by different surface balance designs, typically interconnecting various com...

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Main Authors: Cristina García-Mouton, Mercedes Echaide, Luis A. Serrano, Guillermo Orellana, Fabrizio Salomone, Francesca Ricci, Barbara Pioselli, Davide Amidani, Antonio Cruz, Jesús Pérez-Gil
Format: Article
Language:English
Published: MDPI AG 2023-01-01
Series:Pharmaceutics
Subjects:
Online Access:https://www.mdpi.com/1999-4923/15/1/256
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author Cristina García-Mouton
Mercedes Echaide
Luis A. Serrano
Guillermo Orellana
Fabrizio Salomone
Francesca Ricci
Barbara Pioselli
Davide Amidani
Antonio Cruz
Jesús Pérez-Gil
author_facet Cristina García-Mouton
Mercedes Echaide
Luis A. Serrano
Guillermo Orellana
Fabrizio Salomone
Francesca Ricci
Barbara Pioselli
Davide Amidani
Antonio Cruz
Jesús Pérez-Gil
author_sort Cristina García-Mouton
collection DOAJ
description Pulmonary surfactant (PS) has been proposed as an efficient drug delivery vehicle for inhaled therapies. Its ability to adsorb and spread interfacially and transport different drugs associated with it has been studied mainly by different surface balance designs, typically interconnecting various compartments by interfacial paper bridges, mimicking in vitro the respiratory air–liquid interface. It has been demonstrated that only a monomolecular surface layer of PS/drug is able to cross this bridge. However, surfactant films are typically organized as multi-layered structures associated with the interface. The aim of this work was to explore the contribution of surface-associated structures to the spreading of PS and the transport of drugs. We have designed a novel vehiculization balance in which donor and recipient compartments are connected by a whole three-dimensional layer of liquid and not only by an interfacial bridge. By combining different surfactant formulations and liposomes with a fluorescent lipid dye and a model hydrophobic drug, budesonide (BUD), we observed that the use of the bridge significantly reduced the transfer of lipids and drug through the air–liquid interface in comparison to what can be spread through a fully open interfacial liquid layer. We conclude that three-dimensional structures connected to the surfactant interfacial film can provide an important additional contribution to interfacial delivery, as they are able to transport significant amounts of lipids and drugs during surfactant spreading.
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spelling doaj.art-93795d80df1447528e8bb099804d4e542023-11-30T23:59:52ZengMDPI AGPharmaceutics1999-49232023-01-0115125610.3390/pharmaceutics15010256Beyond the Interface: Improved Pulmonary Surfactant-Assisted Drug Delivery through Surface-Associated StructuresCristina García-Mouton0Mercedes Echaide1Luis A. Serrano2Guillermo Orellana3Fabrizio Salomone4Francesca Ricci5Barbara Pioselli6Davide Amidani7Antonio Cruz8Jesús Pérez-Gil9Department of Biochemistry, Faculty of Biology, and Research Institute “Hospital 12 de Octubre (imas12)”, Complutense University, 28040 Madrid, SpainDepartment of Biochemistry, Faculty of Biology, and Research Institute “Hospital 12 de Octubre (imas12)”, Complutense University, 28040 Madrid, SpainDepartment of Organic Chemistry, Faculty of Chemistry, Complutense University, 28040 Madrid, SpainDepartment of Organic Chemistry, Faculty of Chemistry, Complutense University, 28040 Madrid, SpainR&D Department, Chiesi Farmaceutici, 43122 Parma, ItalyR&D Department, Chiesi Farmaceutici, 43122 Parma, ItalyR&D Department, Chiesi Farmaceutici, 43122 Parma, ItalyR&D Department, Chiesi Farmaceutici, 43122 Parma, ItalyDepartment of Biochemistry, Faculty of Biology, and Research Institute “Hospital 12 de Octubre (imas12)”, Complutense University, 28040 Madrid, SpainDepartment of Biochemistry, Faculty of Biology, and Research Institute “Hospital 12 de Octubre (imas12)”, Complutense University, 28040 Madrid, SpainPulmonary surfactant (PS) has been proposed as an efficient drug delivery vehicle for inhaled therapies. Its ability to adsorb and spread interfacially and transport different drugs associated with it has been studied mainly by different surface balance designs, typically interconnecting various compartments by interfacial paper bridges, mimicking in vitro the respiratory air–liquid interface. It has been demonstrated that only a monomolecular surface layer of PS/drug is able to cross this bridge. However, surfactant films are typically organized as multi-layered structures associated with the interface. The aim of this work was to explore the contribution of surface-associated structures to the spreading of PS and the transport of drugs. We have designed a novel vehiculization balance in which donor and recipient compartments are connected by a whole three-dimensional layer of liquid and not only by an interfacial bridge. By combining different surfactant formulations and liposomes with a fluorescent lipid dye and a model hydrophobic drug, budesonide (BUD), we observed that the use of the bridge significantly reduced the transfer of lipids and drug through the air–liquid interface in comparison to what can be spread through a fully open interfacial liquid layer. We conclude that three-dimensional structures connected to the surfactant interfacial film can provide an important additional contribution to interfacial delivery, as they are able to transport significant amounts of lipids and drugs during surfactant spreading.https://www.mdpi.com/1999-4923/15/1/256pulmonary surfactantair–liquid interfacesurface balancesurface-associated reservoirinterfacial spreadinginterfacial film
spellingShingle Cristina García-Mouton
Mercedes Echaide
Luis A. Serrano
Guillermo Orellana
Fabrizio Salomone
Francesca Ricci
Barbara Pioselli
Davide Amidani
Antonio Cruz
Jesús Pérez-Gil
Beyond the Interface: Improved Pulmonary Surfactant-Assisted Drug Delivery through Surface-Associated Structures
Pharmaceutics
pulmonary surfactant
air–liquid interface
surface balance
surface-associated reservoir
interfacial spreading
interfacial film
title Beyond the Interface: Improved Pulmonary Surfactant-Assisted Drug Delivery through Surface-Associated Structures
title_full Beyond the Interface: Improved Pulmonary Surfactant-Assisted Drug Delivery through Surface-Associated Structures
title_fullStr Beyond the Interface: Improved Pulmonary Surfactant-Assisted Drug Delivery through Surface-Associated Structures
title_full_unstemmed Beyond the Interface: Improved Pulmonary Surfactant-Assisted Drug Delivery through Surface-Associated Structures
title_short Beyond the Interface: Improved Pulmonary Surfactant-Assisted Drug Delivery through Surface-Associated Structures
title_sort beyond the interface improved pulmonary surfactant assisted drug delivery through surface associated structures
topic pulmonary surfactant
air–liquid interface
surface balance
surface-associated reservoir
interfacial spreading
interfacial film
url https://www.mdpi.com/1999-4923/15/1/256
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