Liposome delivery of aminoglycosides in burn wounds.
The current study evaluated the pharmacodynamics of topically applied antimicrobials incorporated into radiolabeled liposomes. Radiolabeled 125I-phenyldecanoic acid was used in the formulation of small unilamellar liposomes. Sephadex (cross-linked dextran beads) G-50 columns were run to determine the per cent of radioactivity incorporated into liposomes and persistence of radioactive tag on the liposome after two weeks (greater than 95 per cent) remained incorporated. On the day of the experiment, 31 adult Sprague Dawley rats were subjected to a 10 per cent total body surface area full thickness burn (Walker burn model). All rats were treated with topical application of 0.3 milliliters of tobramycin entrapped in 125I-liposomes, and burn wounds were covered with Opsite (Winfield Laboratories). This formulation resulted in each rat receiving 14 milligrams per kilogram of tobramycin with a specific activity of 10.41 microcuries. Rats were sacrificed at several time periods after burn injury (nine after 24 hours, 12 after 48 hours, 11 after 72 hours). At these time intervals, serum and tissue tobramycin levels were measured, burn dressing, burn tissue and splanchnic organs were harvested and radioactivity was assessed with a gamma scintillation counter to determine tissue concentration of 125I-liposome tobramycin. Concentration of tobramycin in the serum was negligible at 24, 48 and 72 hours postburn, but was significant in the burn tissues at these times. The radioactive recovery data demonstrated that the majority (greater than 90 per cent) of the recovered liposomes remained at the site of application (the burn wound). No splanchnic organs had greater than 2 per cent of the recovered 125I-liposomes at any time period. These data suggest that, in burn wounds, tobramycin incorporated into liposomes remain at the site of initial application, resulting in high local concentrations with little systemic absorption and confirm that liposomes provide an effective vehicle for delivery of antimicrobials at the site of the burn injury.