INCORPORATION, RELEASE AND IN-VITRO ANTIBACTERIAL ACTIVITY OF LIPOSOMAL AMINOGLYCOSIDES AGAINST PSEUDOMONAS-AERUGINOSA

Amikacin, netilmicin and tobramycin were incorporated into either anio nic or cationic liposomes prepared by sonication. The influence of lip id constituents (charges) on encapsulation efficiency was determined a fter lysis of vesicles by 0.2% (v/v) Triton X-100. The in-vitro activi ties of the liposomal aminoglycosides were evaluated against Pseudomon as aeruginosa by agar dilution and compared with free antibiotics. Nor mal human pooled sera, incubated at 37 degrees C, were supplemented wi th anionic or cationic liposomes containing known fixed concentrations of amikacin, netilmicin or tobramycin. At various time intervals (0-4 8 h), samples were taken and antibiotic concentrations determined by t he enzyme multiplied immunoassay technique (EMIT). The encapsulation e fficiency 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 liposome s 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 i ncubation at 37 degrees C under 5% CO2. The MICs of amikacin (2, 16 an d 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 w hich the MIC was increased eight-fold. Empty cationic or anionic lipos omes had no effect on bacterial growth. Cationic liposomes containing aminoglycosides should be evaluated further for the treatment of pseud omonal infection.