Treatment of experimental salmonellosis in mice with streptomycin entrapped in liposomes.

Liposome-entrapped streptomycin (SM) was compared with free SM for therapeutic efficacy against experimental salmonellosis in mice. All of the mice infected with the virulent strain of Salmonella enteritidis 116-54 died between days 5 and 7, and a dose of 20 mg of free SM per kg administered 24 h after the bacterial inoculation did not prolong the survival. In contrast, the same dose of SM entrapped in liposomes prolonged paralleled the dose in the liposomes, and a dose as low as 1.2 mg of SM per kg in liposomes prolonged the survival. The advantage of using liposomes was more pronounced when a larger dose of SM was employed. The liposome-entrapped drug was less toxic than the free drug. A dose of 80 mg of free SM per kg caused convulsions, but the same dose entrapped in liposomes caused no side effects. Furthermore, two doses of liposome-entrapped SM further enhanced the therapeutic effect. The efficacy of the liposome-entrapped drug was still observed in mice infected with a large inoculum of S. enteritidis. A tissue distribution study on SM in various organs demonstrated that liposomal SM was selectively delivered to the spleen and liver with concentrations in these those in mice receiving the free drug. The prolongation of survival was due to suppression of the multiplication of S. enteritidis as demonstrated by viable cell counts in the spleens.