Biophysical Society Thematic Meeting - October 13-15, 2015

Biophysics of Proteins at Surfaces: Assembly, Activation, Signaling

Poster Abstracts

9-POS Board 9 Biosurfaces and Drug Delivery: Evaluating the Effect of Tacrolimus, an Immunosuppressive Drug, on the Structure and Performance of Pulmonary Surfactant Films Alberto Hidalgo 1 , Francesca Salis 2 , Guillermo Orellana 2 , Antonio Cruz 1 .Jesús Pérez-Gil 1 . 1 Dept. de Bioquímica y Biología Molecular I, Universidad Complutense, Madrid, Spain, 2 Dept. de Química Orgánica I, Universidad Complutense, 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). To prevent pulmonary collapse during breathing, PS must adsorb very rapidly into the air-liquid interface and spread efficiently along it. Therefore, it offers unique opportunities to vehiculize different drugs, while hiding and protecting them from clearance. It has been well established that surfactant proteins ensure a proper PS behaviour and are essential to maintain the integrity of PS. Alterations, deficiencies, or the lack of surfactant proteins produce severe dysfunctions in the respiratory process. The interaction of inhaled entities with surfactant films may perturb structure and performance of surfactant layers, compromising the respiratory function. Therefore, it is crucial to analyse whether each particular molecule delivered to the lung, or transported by surfactant, could somehow affect structure- function determinants in PS. In the present work we have evaluated the effect of Tacrolimus, an immunosuppressive drug, on interfacial DPPC films and on interfacial layers made of a porcine PS extract (containing the hydrophobic proteins SP-B and SP-C). We mainly looked for structural and functional changes associated with the impact of the drug on surfactant activity. In parallel, we evaluated the drug transporting capabilities of PS along the air-water interface, using a novel setup designed in our laboratory. Tacrolimus affects the lateral structure of surfactant films, but after repetitive compression- expansion cycles, this effect was apparently reverted, suggesting that the surface was progresively depurated from the drug. The results suggest that PS could be optimized as a drug- delivery agent with the potential of liberating the drug once subjected to compression-expansion dynamics at the distal airways.

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