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A new drug delivery system (lipid microcarriers) was studied in an experimental model of infected soft tissue wounds. Superficial, nonlethal infection was produced in the adult rat by injecting 1 ml containing 10(8) colony-forming units (CFU) of Pseudomonas aeruginosa under the superficial fascia of the paraspinus muscle of a 2-cm2 excised wound. All wounds were dressed with N-Terface, a nonadherent wound material, and covered with Kontor sponge, an open-cell polyurethane sponge containing either normal saline (group I), free tobramycin (groups III and V), liposome-entrapped tobramycin (groups II and IV), silver sulfadiazene (group VI), or liposome-entrapped silver sulfadiazene (group VII). At 24, 48, and 72 hr postinjection, animals were sacrificed and colony-forming units of P. aeruginosa per gram of muscle tissue were determined. Group I had significantly higher colony-forming units of P. aeruginosa per gram than groups II and III at 48 and 72 hr and than groups IV and V at all times. One single dose of liposome-encapsulated silver sulfadiazine significantly decreased bacterial counts compared to untreated controls and, to a similar extent, compared to multiple applications of free drug. Colony-forming units in all treatment groups (II and III, IV and V, VI and VII) were similar at all time periods within equivalent dosages. The ability of one application of liposomal-entrapped antibiotics to result in a therapeutic effect that requires multiple applications of topically applied free antibiotics offers potential clinical advantages.