title: Synthesis, characterization and in vitro evaluation of amphiphilic ion pairs of erythromycin and kanamycin antibiotics with liposaccharides.
abstract: The hydrophilic ion paring strategy (HIP) is a method explored to improve the cell/tissue uptake of poorly adsorbed drugs and to optimize their physico-chemical characteristics. In this context, we here describe the synthesis of some ion pairs of two model cationic antibiotics, erythromycin (ERY) and kanamycin A (KAN), with liposaccharides having different levels of lipophilicity and charge. The formation of drug-liposaccharide complexes was confirmed by Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD) analysis. The effect of the amphiphilic liposaccharide moieties on the antimicrobial activity of ERY and KAN was assessed by measuring the minimal inhibitory concentration (MIC) of the compounds against a panel of bacterial strains that were susceptible or resistant to the parent antibiotics. The ion pairing did not depress the in vitro antibiotic activity, although no lowering of MIC values was registered. The experimental findings would motivate the future investigation of this ion pairing strategy in drug design, for instance allowing improvement of the encapsulation efficiency of hydrophilic antibiotics in lipid-based nanocarriers, or changing their in vivo biodistribution and pharmacokinetic profile.
authors.affiliation: Section of Pharmaceutical Technology, Department of Drug Sciences, University of Catania, viale A. Doria, 6, 95125 Catania, Italy; NANO-i - Research Centre on Ocular Nanotechnology, University of Catania, 95125 Catania, Italy. Electronic address: r.pignatello@unict.it.
authors.forename: Rosario
authors.initials: R
authors.lastname: Pignatello
authors.affiliation: The School of Chemistry and Molecular Biosciences (SCMB), The University of Queensland, Brisbane, Queensland 4072, Australia.
authors.forename: Pavla
authors.initials: P
authors.lastname: Simerska
authors.affiliation: Section of Pharmaceutical Technology, Department of Drug Sciences, University of Catania, viale A. Doria, 6, 95125 Catania, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Leonardi
authors.affiliation: The School of Chemistry and Molecular Biosciences (SCMB), The University of Queensland, Brisbane, Queensland 4072, Australia.
authors.forename: Adel S
authors.initials: AS
authors.lastname: Abdelrahim
authors.affiliation: IRCCS San Raffaele Pisana, BioBIM - Multidisciplinary Interinstitutional BioBank, Rome, Italy.
authors.forename: Giulio Petronio
authors.initials: GP
authors.lastname: Petronio
authors.affiliation: Section of Microbiology, Department of Biomedical and Biotechnological Sciences - BIOMETEC, University of Catania, via Androne, 81, 95124 Catania, Italy.
authors.forename: Virginia
authors.initials: V
authors.lastname: Fuochi
authors.affiliation: Section of Microbiology, Department of Biomedical and Biotechnological Sciences - BIOMETEC, University of Catania, via Androne, 81, 95124 Catania, Italy.
authors.forename: Pio Maria
authors.initials: PM
authors.lastname: Furneri
authors.affiliation: Nanomedicine Group, Te.Far.T.I. Center, Department of Life Sciences, University of Modena and Reggio Emilia, 41124 Modena, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Ruozi
authors.affiliation: The School of Chemistry and Molecular Biosciences (SCMB), The University of Queensland, Brisbane, Queensland 4072, Australia; The School of Pharmacy, The University of Queensland, Brisbane, Queensland 4072, Australia; The Institute for Molecular Biosciences, The University of Queensland, Brisbane, Queensland 4072, Australia.
authors.forename: Istvan
authors.initials: I
authors.lastname: Toth
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000493:pharmacokinetics*; D004917:Erythromycin / Q000737:chemistry / Q000493:pharmacokinetics*; D057927:Hydrophobic and Hydrophilic Interactions; D007612:Kanamycin / Q000737:chemistry / Q000493:pharmacokinetics*; D008070:Lipopolysaccharides / Q000737:chemistry; D008826:Microbial Sensitivity Tests; D014018:Tissue Distribution
chemical_list: D000900:Anti-Bacterial Agents; D008070:Lipopolysaccharides; D007612:Kanamycin; D004917:Erythromycin
keywords: Amphiphilicity; Antimicrobial activity; Charged liposaccharide; Erythromycin; Kanamycin A; Lipoamino acid