Efficacy of neutral and negatively charged liposome-loaded gentamicin on planktonic bacteria and biofilm communities

Moayad Alhariri,1 Majed A Majrashi,2 Ali H Bahkali,3 Faisal S Almajed,4 Ali O Azghani,5 Mohammad A Khiyami,2 Essam J Alyamani,2 Sameera M Aljohani,6 Majed A Halwani1 1Nanomedicine Department, King Abdullah International Medical Research Center (KAIMRC), King Saud bin Abdulaziz University for Health Sciences, 2National Centre for Biotechnology, Life Sciences and Environment Research Institute, King Abdulaziz City for Science and Technology (KACST), 3Botany and Microbiology Department, College of Science, King Saud University, 4Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Saud bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Center, Riyadh, Saudi Arabia; 5Department of Biology, The University of Texas at Tyler, Tyler, TX, USA; 6College of Science and Health Professions, King Saud bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Center, Riyadh, Saudi Arabia Abstract: We investigated the efficacy of liposomal gentamicin formulations of different surface charges against Pseudomonas aeruginosa and Klebsiella oxytoca. The liposomal gentamicin formulations were prepared by the dehydration–rehydration method, and their sizes and zeta potential were measured. Gentamicin encapsulation efficiency inside the liposomal formulations was determined by microbiologic assay, and stability of the formulations in biologic fluid was evaluated for a period of 48 h. The minimum inhibitory concentration and the minimum bactericidal concentration were determined, and the in vitro time kill studies of the free form of gentamicin and liposomal gentamicin formulations were performed. The activities of liposomal gentamicin in preventing and reducing biofilm-forming P. aeruginosa and K. oxytoca were compared to those of free antibiotic. The sizes of the liposomal formulations ranged from 625 to 806.6 nm in diameter, with the zeta potential ranging from –0.22 to –31.7 mV. Gentamicin encapsulation efficiency inside the liposomal formulation ranged from 1.8% to 43.6%. The liposomes retained >60% of their gentamicin content during the 48 h time period. The minimum inhibitory concentration of neutral formulation was lower than that of free gentamicin (0.25 versus 1 mg/L for P. aeruginosa and 0.5 versus 1 mg/L for K. oxytoca). The negatively charged formulation exhibited the same bacteriostatic concentration as that of free gentamicin. The minimum bactericidal concentration of neutral liposomes on planktonic bacterial culture was twofold lower than that of free gentamicin, whereas the negatively charged formulations were comparable to free gentamicin. The killing time curve values for the neutral negatively charged formulation against planktonic P. aeruginosa and K. oxytoca were better than those of free gentamicin. Furthermore, liposomal formulations prevent the biofilm-formation ability of these strains better than free gentamicin. In summary, liposomal formulations could be an effective lipid nanoparticle to combat acute infections where planktonic bacteria are predominant. Keywords: drug delivery, stability, antibacterial activity, biofil

Cystic fibrosis and physiological responses to exercise.

Journal ArticleCopyright © 2014 Informa Plc. All rights reserved.Cardiopulmonary exercise testing is underutilized within the clinical management of patients with cystic fibrosis. But within the last 5 years, there has been considerable interest in its implementation, which has included deliberations by the European Cystic Fibrosis Society about incorporating this method within the clinical assessment of patients. This review examines the current use of cardiopulmonary exercise testing in assessing the extent and cause(s) of exercise limitation from a pediatric perspective. Examples of the measured parameters and their interpretation are provided. Critical synthesis of recent work in the oxygen uptake (VO2) kinetics response to and following exercise is also discussed, and although identified more as a research tool, its utilization advances researchers understanding of the cardiovascular, respiratory and muscular limitations to exercise tolerance. Finally, exercise and its application in therapeutic interventions are highlighted and a number of recommendations made about the utility of exercise prescription