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 h ave been the nephro- and oto-toxicities and the increasing bacterial r esistance. It has been shown that encapsulation of drugs into liposome s 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, therefo re, encapsulated these drugs into liposomes prepared by sonication. Th e drug contained in liposomes was measured by enzyme multiplied immuno assay technique (EMIT) after lysis of the vesicles by 0.2% Triton X-10 0. The comparative encapsulation efficiency of the three antibiotic pr eparations was assessed. Aminoglycosides kinetic release from liposome s 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 determine d and compared to those of respective free drugs using an agar dilutio n method. The amikacin and tobramycin encapsulation efficiencies were significantly (p less than or equal to 0.05) higher (5.36% +/- 0.17 an d 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 am ikacin (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 t he study. The MICs of liposomal netilmicin against all bacterial strai ns tested were reduced, compared to those of free netilmicin. However, liposomal amikacin and tobramycin MICs were nearly similar to those o f free respective drugs. Overall, liposomal netilmicin appears to be a promising approach in the management of Gram-positive and Gram-negati ve bacterial infections and should be further evaluated in vivo experi ments.