Biophysical Society Thematic Meeting | Ascona, Switzerland

Liposomes, Exosomes, and Virosomes: From Modeling Complex Membrane Processes to Medical Diagnostics and Drug Delivery

Poster Abstracts

30-POS Board 15 Pulmonary Surfactant: A Shuttle to Deliver Drugs into Lung Airspaces

Alberto Hidalgo 1 , Guillermo Orellana 2 , Francesca Salis 2 , Jesus Perez-Gil 1 , Antonio Cruz 1 . 1 Universidad Complutense de Madrid. Faculty of Biology, Madrid, Madrid, Spain, 2 Universidad Complutense de Madrid. Faculty of Chemistry, Madrid, Madrid, Spain. The respiratory surface of the mammalian lung is covered by a thin aqueous layer and, on top of it, by a lipid-protein surface active material, the pulmonary surfactant (PS). Apart from preventing pulmonary collapse during breathing, PS is able to adsorb very rapidly (in few seconds) into the air-liquid interface and, once there, to spread efficiently along it. Therefore, it offers novel opportunities to vehiculize different drugs and nanocarriers, while hiding and protecting them from clearance in the lung. As PS is mainly composed by lipids, hydrophobic drugs can be directly vehiculized into PS membranes while hydrophilic drugs need to be encapsulated into proper containers prior to their integration into pulmonary surfactant. In the present work we have evaluated the possibilities of vehiculizing model liposomes containing calceine as a model carrier for the delivery of hydrophilic probes, and the vehiculization of tacrolimus as a hydrophobic model drug. When we analysed structural and functional changes associated with the presence of the drug into PS, we observed that tacrolimus affects the lateral structure of DPPC and surfactant interfacial films. It inhibits the compression-driven segregation of domains associated with expanded-to-condensed lateral phase transitions. Interestingly, after some compression- expansion cycles, this effect is apparently reverted, suggesting that surfactant films can be progressively refined and depurated from the drug during interfacial dynamics. Experiments performed in a modified Wilhelmy balance show that only in the presence of PS, the drug travels along the air-liquid interface. Therefore, we suggest that, once the drugs are transported by surfactant along the respiratory surface to the distal airways, breathing dynamics could facilitate the progressive drug release.

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