Preparation and Microbiological Evaluation of Amphiphilic Kanamycin-Lipoamino Acid Ion-Pairs

Abstract

Amphiphilic ion-pairs of kanamycin (KAN) were prepared by evaporation of a water-ethanol co-solution of KAN base and a lipoamino acid bearing a 12-carbon atoms alkyl side chain (LAA12), at different molar ratios. Infrared spectroscopy confirmed the structure of ion-pairs, while differential scanning calorimetry (DSC) and powder X-ray diffractometry (PXRD) studies supported the formation of new saline species with a different crystalline structure than the starting components. The solubility pattern shown in a range of both aqueous and organic solvents confirmed that the ion-pairs possess an amphiphilic character. The LAA12 counter-ion showed not to improve the antibacterial activity of KAN, suggesting that such chemical strategy is not able to favor the penetration of this drug inside the bacteria cells. Nevertheless, a slight improving, i.e., a one-fold dilution, was observed in E. coli. The present study can also serve as the basis for a further evaluation of LAA ion-pairing of antibiotics, as a means to improve the loading of hydrophilic drugs into lipid-based nanocarriers.

Kanamycin complexation with cellulose acetate sulphate: a promissing way from injectable to oral form of antibiotic

“…The particles hydrodynamic size in the solutions of Na-CAS and in the sols of its complexes with KAN, obtained by mixing of solutions with Na-CAS concentration of 2 • 10 -5 mol/dm 3 and AB concentration corresponding to the compositions of the complexes, were estimated using laser diffraction method on a Zetasizer nano ZS device (Malvern, UK) at the temperature 298 K. The kinetics of the complex particles growth was evaluated by a Mastersizer 3000 laser particle size analyser (Malvern) using a wet dispersion unit with a measuring vessel volume of 120 cm 3 at a rotation speed of 1500 min -1 . The formation of complex particles dispersions resulted directly in the vessel by adding of the polymer solution (0.02 mol/dm 3 ) to the AB solution with the concentration of 0.002 mol/dm 3 and by different mixing order. The particles size distribution was also estimated by the analysis of motion trajectory of nanoparticles on a Nanosight LM0 multiparametric analyser of nanoparticles (Nanosight Ltd., UK) in the HS -BF configuration (Andor Luca high-sensitivity video camera; a semiconductor laser with a wavelength of 405 nm and a power of 45 mW).…”

“…Using the hydrophobic ion-pairing in drug molecules containing ionisable groups, polar counter-ions are stoichiometrically replaced with lipophilic ones. The modification by lipoamino acid was described for aminoglycoside AB kanamycin [3].…”