Journal of Antimicrobial Chemotherapy (1995) 36, 631-639
© 1995 The British Society for Antimicrobial Chemotherapy
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Incorporation, release and in-vitro antibacterial activity of liposomal aminoglycosides against Pseudomonas aeruginosa
aDepartment of Microbiology Hotel-Dieu Hospital of Montreal, 3840 St-Urbain, Montréal, Quebec, H2W1T8; bDepartments of Pharmacology University of Montreal, Montreal, Quebec, Canada cMicrobiology and Immunology University of Montreal, Montreal, Quebec, Canada
returned 10 March 1995; accepted 15 May 1995
*Corresponding author. Phone: + 1-(514) 843 2675; Fax: + 1-(514) 849 8986.
Amikacin, netilmicin and tobramycin were incorporated into either anionic or cationic liposomes prepared by sonication. The influence of lipid constituents (charges) on encapsulation efficiency was determined after lysis of vesicles by 0.2% (v/v) Triton X-100. The in-vitro activities of the liposomal aminoglycosides were evaluated against Pseudomonas aeruginosa by agar dilution and compared with free antibiotics. Normal human pooled sera, incubated at 37°C, were supplemented with anionic or cationic liposomes containing known fixed concentrations of amikacin, netilmicin or tobramycin. At various time intervals (0–48 h), samples were taken and antibiotic concentrations determined by the enzyme multiplied immunoassay technique (EMIT). The encapsulation efficiency of cationic liposomes (amikacin 17.1 ± 1.55%, netilmicin: 5.63 ± 1.13%, tobramycin 6.7 ± 0.5%) was approximately 30% higher than that of anionic liposomes (amikacin 12.3 ±0.95%, netilmicin 4.0 ± 0.06%, tobramycin 5.13 ±0.18%). Anionic and cationic liposomes in human serum still retained 79.13 ±4.04% and 82.71 ± 2.6% of amikacin, 50.67 ± 1.8% and 38.6 ± 0.8% of netilmicin, and 89.09 ± 1.0% and 88.93 ± 0.4% of tobramycin, respectively, after 48 h of incubation at 37°C under 5% CO2. The MICs of amikacin (2, 16 and 2 mg/L), netilmicin (2, 1 and 4 mg/L) and tobramycin (1,2 and 4 mg/L) in free, anionic or cationic liposomal formulations, respectively, were relatively comparable except for anionic liposomal amikacin for which the MIC was increased eight-fold. Empty cationic or anionic liposomes had no effect on bacterial growth. Cationic liposomes containing aminoglycosides should be evaluated further for the treatment of pseudomonal infection.
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