201. Interaction of levofloxacin with lung surfactant at the air-water interface
- Author
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Osvaldo N. Oliveira, Alline A. Pedreira, André S. Pimentel, Stephanie Ortiz-Collazos, Paulo H. S. Picciani, and Evelina D. Estrada-López
- Subjects
PNEUMONIA ,Langmuir ,1,2-Dipalmitoylphosphatidylcholine ,Spectrophotometry, Infrared ,Surface Properties ,Levofloxacin ,Molecular Dynamics Simulation ,010402 general chemistry ,01 natural sciences ,Surface-Active Agents ,chemistry.chemical_compound ,Colloid and Surface Chemistry ,Adsorption ,Pulmonary surfactant ,0103 physical sciences ,Monolayer ,medicine ,Physical and Theoretical Chemistry ,POPC ,Lung ,Chromatography ,010304 chemical physics ,Chemistry ,Water ,Pulmonary Surfactants ,Surfaces and Interfaces ,General Medicine ,biochemical phenomena, metabolism, and nutrition ,bacterial infections and mycoses ,0104 chemical sciences ,medicine.anatomical_structure ,Chemical engineering ,Drug delivery ,Biotechnology ,medicine.drug - Abstract
The molecular-level interaction of levofloxacin with lung surfactant was investigated using Langmuir monolayers and atomistic molecular dynamics (MD) simulations. In the simulation, the DPPC/POPC mixed monolayer was used as a lung surfactant model and the molecules of levofloxacin were placed at the air-lipid interface to mimic the adsorption process on the lung surfactant model. The simulation results indicate that amphoteric levofloxacin expands the lung surfactant, also stabilizing the film for levofloxacin fractions until 10% w/w at least. The Langmuir monolayers made with the lung surfactant Curosurf had expanded isotherms upon incorporation of levofloxacin, without changes in monolayer elasticity. In fact, levofloxacin induced film stability with increased collapse pressures in the Curosurf isotherms and delayed the phase transition, according to Brewster angle microscopy (BAM) imaging. Using polarization-modulated infrared reflection-absorption spectroscopy (PM-IRRAS), we found that levofloxacin is preferentially located in the head group region, inducing an increased organization of the Curosurf film. This location of levofloxacin was confirmed with MD simulations. The stability inferred demonstrates that the lung surfactant can be used as a drug delivery system for the administration via inhalation or intratracheal instillation of levofloxacin to treat lung diseases such as pneumonia and respiratory distress syndrome.
- Published
- 2017