Departamento de Química, Pontifícia Universidade Católica do Rio de Janeiro, Rio de Janeiro, RJ 22453-900, Brazil.
Instituto de Macromoléculas Professora Eloisa Mano, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ 21941-598, Brazil.
Colloids Surf B Biointerfaces. 2017 Oct 1;158:689-696. doi: 10.1016/j.colsurfb.2017.07.066. Epub 2017 Jul 27.
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.
采用 Langmuir 单分子层和原子分子动力学（MD）模拟研究了左氧氟沙星与肺表面活性剂的分子水平相互作用。在模拟中，DPPC/POPC 混合单层被用作肺表面活性剂模型，将左氧氟沙星分子置于气-脂界面以模拟在肺表面活性剂模型上的吸附过程。模拟结果表明，两性左氧氟沙星扩展了肺表面活性剂，并且至少在 10%w/w 的左氧氟沙星分数下稳定了膜。在掺入左氧氟沙星后，用肺表面活性剂 Curosurf 制成的 Langmuir 单分子层的等温线扩张，而单层弹性没有变化。实际上，根据布鲁斯特角显微镜（BAM）成像，左氧氟沙星诱导了 Curosurf 等温线中的膜稳定性增加和相变延迟。使用偏振调制红外反射吸收光谱（PM-IRRAS），我们发现左氧氟沙星优先位于头部基团区域，从而增加了 Curosurf 膜的组织。通过 MD 模拟证实了左氧氟沙星的这种位置。这种稳定性表明肺表面活性剂可用作药物递送系统，通过吸入或气管内滴注来输送左氧氟沙星，以治疗肺炎和呼吸窘迫综合征等肺部疾病。
