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JAC Advance Access published online on December 8, 2004
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkh518
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JAC © The British Society for Antimicrobial Chemotherapy 2004; all rights reserved
Received August 5, 2004
Revised October 27, 2004
Accepted October 28, 2004

Brief report

Liposome-mediated gentamicin delivery: development and activity against resistant strains of Pseudomonas aeruginosa isolated from cystic fibrosis patients

Clement Mugabe 1, Ali O. Azghani 2, and Abdelwahab Omri 1*

1 The Novel Drug&Vaccine Delivery Systems Facility, Department of Chemistry and Biochemistry, Laurentian University, 935 Ramsey Lake Rd, Sudbury, Ontario, P3E 2C6, Canada
2 The University of Texas Health Center, Department of Medicine, 11937 US Highway 271, Tyler, Texas 75708, USA

* To whom correspondence should be addressed.
Abdelwahab Omri, E-mail: aomri{at}nickel.laurentian.ca


  Abstract

Objectives: Chronic pulmonary infection by Pseudomonas aeruginosa in cystic fibrosis patients is virtually impossible to eradicate by means of existing free antibiotics. We sought to assess the antibacterial activities of liposomal gentamicin against clinical isolates of P. aeruginosa.

Methods: Gentamicin was encapsulated into liposomes with different lipid compositions (1,2-dimyristoyl-sn-glycero-3-phosphocholine, 1,2-dipalmitoyl-sn-glycero-3-phosphocholine and 1,2-distearoyl-sn-glycero-3-phosphocholine) and cholesterol in the molar ratio of 2:1 by sonication. The in vitro stability of liposome-encapsulated gentamicin was studied over a 48 h period at 4 and 37°C in PBS and at 37°C in pooled plasma. The MICs of free and liposomal gentamicin for clinical isolates of P. aeruginosa were assessed by broth dilution.

Results: The encapsulation efficiency of all liposomal preparations was 4%-5.18% of the initial amount of the drug in solution. The liposomes retained 60%-70% of the encapsulated gentamicin for 48 h when they were incubated in normal human pooled plasma or PBS at 4 or 37°C. The MICs of liposomal gentamicin for all clinical isolates of P. aeruginosa were lower than the MICs of free gentamicin. Importantly, liposomal gentamicin altered the susceptibilities of these clinical isolates from gentamicin resistant to either intermediate or susceptible.

Conclusions: Taken together, these data indicate that liposomal gentamicin formulations could be more effective than the free drug in controlling pulmonary infections due to P. aeruginosa.

Keywords: antibiotic delivery; lung infection; stability.
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