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    Proof of pore formation and biophysical perturbations through a 2D amoxicillin-lipid membrane interaction approach

    Year: 2017

    Journal: Biochim. Biophys. Acta-Biomembr., Volume 1859, MAY, page 803–812

    Authors: Lopes, Daniela; Nunes, Claudia; Fontaine, Philippe; Sarmento, Bruno; Reis, Salette

    Organizations: Fundacao para a Ciencia e Tecnologia (FCT) [PD/BD/105957/2014, SFRH/BPD/81963/2011]; FCT through the FCT PhD Programmes; Programa Operational Capital Humano (POCH); BiotechHealth Programe (Doctoral Programme on Cellular and Molecular Biotechnology Applied to Health Sciences) [PD/00016/2012]; European Union [POCI/01/0145/FEDER/007728]; National Fund (FCT/MEC) [UID/MULTI/04378/2013]; National Fund (Fundacao para a Ciencia e Tecnologia) [UID/MULTI/04378/2013]; National Fund (Ministerio da Educacao e Ciencia) [UID/MULTI/04378/2013]; CALIPSO founded program [20140683]

    Keywords: amoxicillin; biophysics; monolayers; pores

    Amoxicillin is a worldwide used antibiotic, and it is classified as a first-line drug against Helicobacter pylori gastric infections. However, the current treatment of these infections has several limitations, such as the side effects and the low therapeutic compliance. Amoxicillin has been associated with gastrointestinal and renal side effects, with higher toxicity when the pH is lower. By considering this association and the well-known pH gradient of the gastric mucosa, this work aims to evaluate the influence of pH on the toxicity of amoxicillin. For that purpose, 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) monolayers were used since phosphatidylcholines are the most common phospholipid headgroup of biological membranes. To have insight of the effects of amoxicillin, different techniques were employed, namely, isotherm measurements, infrared reflection-absorption spectroscopy, grazing incident X-ray diffraction and Brewster angle microscopy. The monolayers of DPPC spread onto different buffer solutions (pH 1.2, pH 5 and pH 7.4) showed different structural and packing properties. The interaction with amoxicillin also depended on the pH. At pH 7.4, the highest effect was visualized at lower pressures, with partial restoration of the biophysical properties of the monolayer at 30 mN.m(-1). A higher perturbation is shown at acidic pH, in which pores were visualized by Brewster angle microscopy. These perturbations may ultimately be related with amoxicillin toxicity. (C) 2017 Elsevier B.V. All rights reserved.
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