Amphiphilic Erythromycin-Lipoamino Acid Ion Pairs: Characterization and In Vitro Microbiological Evaluation

A series of amphiphilic ion pairs of erythromycin (ERY) with lipoamino acids (LAAs) wereproduced. The ion pairs were prepared by evaporation of a water/ethanol co-solution of the drug andLAA bearing an alkyl side chain of 10–16 carbon atoms. For the sake of comparison, equimolar physicalmixtures were prepared by triturating ERY and the LAA in the absence of any solvent. FTIRspectroscopy confirmed the structure of ion pairs, while differential scanning calorimetry and powder Xraydiffractometry were used to assess the formation of new saline species. The solubility pattern of thecoevaporates in different aqueous and organic solvents confirmed their amphiphilic properties. ERY–LAA ion pairs were submitted to an in vitro microbiological assay against different bacterial strains, bothsusceptible and resistant to macrolides. The presence of the LAA moiety was shown not altering theantibacterial spectrum of activity of the drug. These results can be the basis for a further evaluation ofERY–LAA ion pairs as a mean to improve the penetration of the drug inside bacterial cells and tooptimize the loading of ERY in lipid-based nanocarriers.