109 / 120
Liposomes, Exosomes, and Virosomes: From Modeling Complex
Membrane Processes to Medical Diagnostics and Drug Delivery
Poster Abstracts
104
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.