Biological evaluation of pyrazinamide liposomes for treatment of Mycobacterium tuberculosis.

Pyrazinamide liposomes were prepared employing the phospholipid molar ratios; dipalmitoyl phosphatidyl choline (7):cholesterol (2) neutral and dipalmitoyl phosphatidyl choline (7):cholesterol (2):dicetyl phosphate (1) negatively charged. Swelling at 52 degrees C led to higher trapping efficiencies. An optimum sterilizing dose of 25 kGy was exhibited by gamma (gamma)-irradiation. Neutral pyrazinamide liposomes (7:2), swollen for 24 h, were employed in biological evaluation for treatment of mice infected by Mycobacterium tuberculosis. Liposomal pyrazinamide could effect highly significant reduction in bacterial counts (colony forming units/g lung), 10, 20 and 30 days after the last treatment dose. Histopathological examination of mice lungs showed highest severity of infection in drug-free liposomes (control) group > pyrazinamide liposomes > free pyrazinamide 6 days/week. The results indicate high therapeutic efficacy of pyrazinamide liposomes, injected twice weekly, in treatment of M. tuberculosis in mice.