Preparation, properties and the effects of amikacin, netilmicin and tobramycin in free and liposomal formulations on Gram-negative and Gram-positive bacteria

The most common problems limiting the medical use of aminoglycosides have been the nephro- and oto-toxicities and the increasing bacterial resistance. It has been shown that encapsulation of drugs into liposomes enhances their efficacy while reducing their toxicities. The present in vitro study was designed to evaluate the antimicrobial activities of free and liposomal amikacin, netilmicin and tobramycin. We, therefore, encapsulated these drugs into liposomes prepared by sonication. The drug contained in liposomes was measured by enzyme multiplied immunoassay technique (EMIT) after lysis of the vesicles by 0.2% Triton X-100. The comparative encapsulation efficiency of the three antibiotic preparations was assessed. Aminoglycosides kinetic release from liposomes in presence of normal human sera was also studied in vitro over a 48 h period at 37 degrees C under 5% CO2. The MICs of these encapsulated drugs to Pseudomonas aeruginosa, Xanthomonas maltophilia, Escherichia coli, Streptococcus faecalis and Staphylococcus aureus were determined and compared to those of respective free drugs using an agar dilution method. The amikacin and tobramycin encapsulation efficiencies were significantly (p less than or equal to 0.05) higher (5.36% +/- 0.17 and 5.06% +/- 0.10) than those of netilmicin (3% +/- 0.18). However, in presence of sera, liposomal retention of netilmicin was significantly (P less than or equal to 0.05) lower (61.88 +/- 0.14%) than that of amikacin (81.45 +/- 0.64%) and tobramycin (94.07 +/- 0.18%) after 1 h of incubation and then remained nearly constant over an 48 h period of the study. The MICs of liposomal netilmicin against all bacterial strains tested were reduced, compared to those of free netilmicin. However, liposomal amikacin and tobramycin MICs were nearly similar to those of free respective drugs. Overall, liposomal netilmicin appears to be a promising approach in the management of Gram-positive and Gram-negative bacterial infections and should be further evaluated in vivo experiments.