Interaction of gentamicin with phosphatidylserine/phosphatidylcholine mixtures in adsorption monolayers and thin liquid films: morphology and thermodynamic properties, Eur

ABSTRACT. Aminoglycoside are antibiotics used to treat serious infections caused by aerobic gram-negative bacilli. These antibiotics and especially Gentamicin possess aggressive nephro- and ototoxicity. Gentamicin accumulates in the renal cortex before renal failure. Furthermore calcium reduces Gentamicin binding to cell membranes and dietary calcium reduces Gentamicin nephrotoxicity. Possible molecular mechanism underlying nephro- and ototoxicity is kidney cell membrane fusion, this event strongly depend on the presence of negatively charged phospholipids i.e. phosphatidyleserine. The aim of the current work is to study thermodynamically the interactions of Gentamicine and phosphatidyleserin through nanometer scale thin films, Thin Liquid Films – Bilayer Films (TLFs) and Monolayer Films (MFs). Investigation is concentrated on the effect of Gentamicin on the TLFs stability i.e fusion, MFs surface tension and the influence of calcium ions on the discussed thermodynamic parameters. Important part is focused on the significance of lipid phase-separation for the Gentamicin-phosphatidyleserine interactions. It was found a destabilization effect of Gentamicin on PS TLF and alternatively a stabilization effect of Gentamicin on the phase separated TLFs formed from dipalmitoylphosphatidylcholine/phosphatidyleserine. No drug effect on the neutral phospholipid TLFs and on all other TLFs in presence of calcium was observed, suggesting strictly electrostatic Gentamicin-phosphatidyleserine interactions both in phase separated and homogenous TLFs. * corresponding autho