AAC
Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Webb, M. S.
Right arrow Articles by Hope, M. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Webb, M. S.
Right arrow Articles by Hope, M. J.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, January 1998, p. 45-52, Vol. 42, No. 1
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Antibacterial Efficacy against an In Vivo Salmonella typhimurium Infection Model and Pharmacokinetics of a Liposomal Ciprofloxacin Formulation

Murray S. Webb,1,* Nancy L. Boman,1 David J. Wiseman,1 Dawn Saxon,1 Kym Sutton,1 Kim F. Wong,2 Patricia Logan,1 and Michael J. Hope1,3

Inex Pharmaceuticals Corporation, Burnaby, British Columbia, Canada V5J 5J81; Liposome Research Unit, Department of Biochemistry, University of British Columbia Vancouver, British Columbia, Canada V6T 4E62; and Skin Barrier Research Laboratory, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada V6T 2B53

Received 7 May 1997/Returned for modification 10 October 1997/Accepted 27 October 1997

The fluoroquinolone antibiotic ciprofloxacin has been encapsulated into large unilamellar vesicles (LUV) at efficiencies approaching 100%. Drug accumulation proceeded in response to a transmembrane gradient of methylammonium sulfate and occurred concomitantly with the efflux of methylamine. A mechanism for the encapsulation process is described. LUV composed of dipalmitoylphosphatidylcholine-cholesterol (DPPC/chol), distearoylphosphatidylcholine-cholesterol (DSPC/chol), or sphingomyelin-cholesterol (SM/chol) increased the circulation lifetime of ciprofloxacin after intravenous (i.v.) administration by >15-fold. The retention of ciprofloxacin in liposomes in the circulation decreased in the sequence SM/chol > DSPC/chol > DPPC/chol. Increased circulation lifetimes were associated with enhanced delivery of the drug to the livers, spleens, kidneys, and lungs of mice. Encapsulation of ciprofloxacin also conferred significant increases in the longevity of the drug in the plasma after intraperitoneal administration and in the lungs after intratracheal administration in comparison to free ciprofloxacin. The efficacy of a single i.v. administration of an SM/chol formulation of ciprofloxacin was measured in a Salmonella typhimurium infection model. At 20 mg of ciprofloxacin per kg of body weight, the encapsulated formulation resulted in 103- to 104-fold fewer viable bacteria in the livers and spleens of infected mice than was observed for animals treated with free ciprofloxacin. These results show the utility of liposomal encapsulation of ciprofloxacin in improving the pharmacokinetics, biodistribution, and antibacterial efficacy of the antibiotic. In addition, these formulations are well suited for i.v., intraperitoneal, and intratracheal or aerosol administration.

* Corresponding author. Mailing address: Inex Pharmaceuticals Corporation, 100-8900 Glenlyon Parkway, Burnaby, British Columbia, Canada V5J 5J8. Phone: (604) 264-9954. Fax: (604) 264-9690. E-mail: mwebb{at}inexpharm.com.

Antimicrobial Agents and Chemotherapy, January 1998, p. 45-52, Vol. 42, No. 1
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:



Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
Clin. Vaccine Immunol. Clin. Microbiol. Rev.
J. Clin. Microbiol. ALL ASM JOURNALS

Copyright © 1998 by the American Society for Microbiology. All rights reserved.