In an experimental infection caused by Listeria monocytogenes in mice a considerable enhancement (90-fold) of the therapeutic activity of ampicillin resulting from liposomal encapsulation was observed. The mechanism by which liposomes improved the therapeutic index of ampicillin in this infection appeared to be an increased delivery of the antibiotic to the site of infection, i.e. the liver and spleen. Substantial amounts of liposomal ampicillin were recovered from isolated Kupffer cells, the target cells of L. monocytogenes after intravenous inoculation. In addition, in studies on the survival of L. monocytogenes within murine peritoneal macrophages in vitro it was found that liposomal encapsulation of ampicillin resulted in an increased availability of the antibiotic for the intracellular bacteria: liposomal ampicillin killed 90% of the intracellular bacteria, whereas a similar concentration of free ampicillin plus empty liposomes had no effect upon the intracellular bacteria.
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