Amphiphilic ion pairs of tobramycin with lipoamino acids

A series of amphiphilic ion pairs of the aminoglycoside antibiotic tobramycin (TOB) with lipoamino acids (LAA) bearing an alkyl side chain of 10–14 carbon atoms are described. TOB-LAA ion pairs were obtained by reduced pressure evaporation of an aqueous-ethanol co-solution of TOB and LAAs. A different degree of substitution of TOB amine groups was obtained by using increasing the drug to LAA molar fractions (1:1 to 1:5). FTIR analysis corroborated their structure, powder X-ray diffractometry (PXRD) and differential scanning calorimetry (DSC) were used to identify the formation of new chemical species.The prepared compounds were submitted to an in vitro microbiological assay against different bacterial strains, both susceptible and resistant to aminoglycosides. The presence of only one LAA moiety did not improve the in vitro antibacterial activity of TOB free base. Analogously, equimolar physical mixtures (PhM) of TOB with LAA failed to exert a remarkable cell growth inhibitory activity.Noteworthy, when three or all the five amine groups of TOB were salified with LAA residues, very active compounds were produced, showing MIC values lower than the detectable limit of 0.03 μg/ml.

Graphical abstractAqueous-ethanol co-solutions of tobramycin and lipoamino acids were evaporated off to obtained amphiphilic ion pairs of the antibacterial drug. The obtained compounds were characterized in the solid state; in vitro, they showed to keep or even improve the antibacterial activity of the drug, in respect to the therapeutically used salts of tobramycin.Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Ion Pairs of tobramycin and lipoamino acids were prepared by coevaporation. ► Compounds were fully characterized in the solid state. ► Evaluated against different reference bacterial strains, vs. a therapeutically used tobramycin salt. ► This ion pairs showed to keep or even improve the in vitro antibacterial activity of the drug.