Shaoning Wang1,2, Shihui Yu2,3, Yuwei Lin4, Peizhi Zou2, Guihong Chai2, Heidi H Yu4, Hasini Wickremasinghe4, Nivedita Shetty2, Junhong Ling1,2, Jian Li4, Qi Tony Zhou5. 1. Department of Medicinal Chemistry, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, 110016, China. 2. Department of Industrial and Physical Pharmacy, College of Pharmacy, Purdue University, 575 Stadium Mall Drive, West Lafayette, Indiana, 47907, USA. 3. Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, 110016, China. 4. Monash Biomedicine Discovery Institute, Department of Microbiology, Monash University, Clayton, VIC, 3800, Australia. 5. Department of Industrial and Physical Pharmacy, College of Pharmacy, Purdue University, 575 Stadium Mall Drive, West Lafayette, Indiana, 47907, USA. tonyzhou@purdue.edu.
Abstract
PURPOSE: This study aims to develop liposomal formulations containing synergistic antibiotics of colistin and ciprofloxacin for the treatment of infections caused by multidrug-resistant Pseudomonas aeruginosa. METHODS: Colistin (Col) and ciprofloxacin (Cip) were co-encapsulated in anionic liposomes by ammonium sulfate gradient. Particle size, encapsulation efficiency, in vitro drug release and in vitro antibiotic activities were evaluated. RESULTS: The optimized liposomal formulation has uniform sizes of approximately 100 nm, with encapsulation efficiency of 67.0% (for colistin) and 85.2% (for ciprofloxacin). Incorporation of anionic lipid (DMPG) markedly increased encapsulation efficiency of colistin (from 5.4 to 67.0%); however, the encapsulation efficiency of ciprofloxacin was independent of DMPG ratio. Incorporation of colistin significantly accelerated the release of ciprofloxacin from the DMPG anionic liposomes. In vitro release of ciprofloxacin and colistin in the bovine serum for 2 h were above 70 and 50%. The cytotoxicity study using A549 cells showed the liposomal formulation is as non-toxic as the drug solutions. Liposomal formulations of combinations had enhanced in vitro antimicrobial activities against multidrug resistant P. aeruginosa than the monotherapies. CONCLUSIONS: Liposomal formulations of two synergistic antibiotics was promising against multidrug resistant P. aeruginosa infections.
PURPOSE: This study aims to develop liposomal formulations containing synergistic antibiotics of colistin and ciprofloxacin for the treatment of infections caused by multidrug-resistant Pseudomonas aeruginosa. METHODS: Colistin (Col) and ciprofloxacin (Cip) were co-encapsulated in anionic liposomes by ammonium sulfate gradient. Particle size, encapsulation efficiency, in vitro drug release and in vitro antibiotic activities were evaluated. RESULTS: The optimized liposomal formulation has uniform sizes of approximately 100 nm, with encapsulation efficiency of 67.0% (for colistin) and 85.2% (for ciprofloxacin). Incorporation of anionic lipid (DMPG) markedly increased encapsulation efficiency of colistin (from 5.4 to 67.0%); however, the encapsulation efficiency of ciprofloxacin was independent of DMPG ratio. Incorporation of colistin significantly accelerated the release of ciprofloxacin from the DMPG anionic liposomes. In vitro release of ciprofloxacin and colistin in the bovine serum for 2 h were above 70 and 50%. The cytotoxicity study using A549 cells showed the liposomal formulation is as non-toxic as the drug solutions. Liposomal formulations of combinations had enhanced in vitro antimicrobial activities against multidrug resistant P. aeruginosa than the monotherapies. CONCLUSIONS: Liposomal formulations of two synergistic antibiotics was promising against multidrug resistant P. aeruginosa infections.
Authors: Jian Li; Craig R Rayner; Roger L Nation; Roxanne J Owen; Denis Spelman; Kar Eng Tan; Lisa Liolios Journal: Antimicrob Agents Chemother Date: 2006-09 Impact factor: 5.191
Authors: Phillip J Bergen; Jurgen B Bulitta; Alan Forrest; Brian T Tsuji; Jian Li; Roger L Nation Journal: Antimicrob Agents Chemother Date: 2010-06-28 Impact factor: 5.191
Authors: Pritesh P Jain; Regina Leber; Chandran Nagaraj; Gerd Leitinger; Bernhard Lehofer; Horst Olschewski; Andrea Olschewski; Ruth Prassl; Leigh M Marsh Journal: Int J Nanomedicine Date: 2014-07-07