Amphiphilic ion pairs of tobramycin with lipoamino acids

Abstract

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.