TUFTSIN-BEARING LIPOSOMES AS RIFAMPIN VEHICLES IN TREATMENT OF TUBERCULOSIS IN MICE

The antitubercular activity of rifampin was considerably increased whe n it was encapsulated in egg phosphatidylcholine liposomes. A further increase in the activity was observed when the macrophage activator te trapeptide tuftsin was grafted on the surface of the drug-loaded lipos omes. Intermittent treatments (twice weekly) with these preparations w ere significantly more effective than the continuous treatments. Rifam pin delivered twice weekly for 2 weeks in tuftsin-bearing liposomes wa s at least 2,000 times more effective than the free drug in lowering t he load of lung bacilli in infected animals. However, pretreatment wit h drug-free tuftsin-bearing liposomes did not render the pretreated an imals resistant to the Mycobacterium tuberculosis infections, neither did it appreciably increase the chemotherapeutic efficacy of the lipos omized rifampin. These results clearly demonstrate that liposome targe ting to macrophages could considerably increase the antitubercular act ivity of liposomized drugs such as rifampin. Also, it shows that immun oprophylactic treatment with macrophage activators such as tuftsin doe s not afford any advantage in treatment of tuberculosis infections, pr esumably because of inactivation of the primed macrophages by the myco bacterial sulfatides.