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.
Biochim Biophys Acta Biomembr. 2019 Oct 1;1861(10):182994. doi: 10.1016/j.bbamem.2019.05.016. Epub 2019 May 28.
Research on lipid/drug interactions at the nanoscale underpins the emergence of synergistic mechanisms for topical drug administration. The structural understanding of bio-mimetic systems employing 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) as a lung surfactant model mixed with antibiotics, as well as their biophysical properties, is of critical importance to modulate the effectiveness of therapeutic agents released directly to the airways. In this paper, we investigate the structural details of the interaction between Levofloxacin, 'a respiratory quinolone', and the macrolide Clarithromycin, with DPPC monolayers at the air-water interface, using a combination of Brewster angle microscopy, polarization modulation-infrared reflection-adsorption spectroscopy (PM-IRRAS), surface pressure isotherms and neutron reflectometry (NR) to describe the structural details of this interaction. The results allowed association of changes in the π-A isotherm profile with changes in the molecular organization and the co-localization of the antibiotics within the lipid monolayer by NR measurements. Overall, both antibiotics are able to increase the thickness of the acyl tails in DPPC monolayers with a corresponding reduction in tail tilt as well as to interact with the phospholipid headgroups as shown by PM-IRRAS experiments. The effects on the DPPC monolayers are correlated with the physical-chemical properties of each antibiotic and dependent on its concentration.
纳米级的脂质/药物相互作用研究为局部药物给药的协同机制的出现提供了基础。对于模拟生物系统的结构理解，使用 1,2-二棕榈酰基-sn-甘油-3-磷酸胆碱（DPPC）作为肺表面活性剂模型与抗生素混合，并研究其生物物理特性，对于调节直接释放到气道中的治疗剂的有效性至关重要。在本文中，我们使用布儒斯特角显微镜、偏振调制红外反射吸收光谱（PM-IRRAS）、表面压力等温线和中子反射（NR）技术，研究了在气/水界面处左氧氟沙星（“呼吸喹诺酮”）和大环内酯类克拉霉素与 DPPC 单层之间的相互作用的结构细节，以描述这种相互作用的结构细节。结果允许通过 NR 测量将π-A 等温线轮廓的变化与抗生素在脂质单层中的分子组织和共定位的变化相关联。总的来说，两种抗生素都能够增加 DPPC 单层中酰基尾部的厚度，同时尾部倾斜度减小，并且如 PM-IRRAS 实验所示，与磷脂头部基团相互作用。对 DPPC 单层的影响与每种抗生素的物理化学性质相关，并取决于其浓度。
