Effective treatment of acute and chronic murine tuberculosis with liposome-encapsulated clofazimine

The therapeutic efficacy of liposomal clofazimine (L-CLF) was studied in mi ce infected with Mycobacterium tuberculosis Erdman, Groups of mice were tre ated with either free clofazimine (F-CLF), L-CLF, or empty liposomes twice a week for five treatments beginning on day 1 (acute), day 21 (established) , or day 90 (chronic) postinfection. One day after the last treatment, the numbers of CFU of M, tuberculosis in the spleen, liver, and lungs were dete rmined. F-CLF at the maximum tolerated dose of 5 mg/kg of body weight was i neffective; however, 10-fold-higher doses of L-CLF demonstrated a dose resp onse with significant CFU reduction in all tissues without any toxic effect s. In acutely infected mice, 50 mg of L-CLF/kg reduced CFU 2 to 3 log units in all three organs. In established or chronic infection, treated mice sho wed no detectable CFU in the spleen or liver and 1- to 2-log-unit reduction in the lungs. A second series of L-CLF treatments cleared M, tuberculosis in all three tissues. L-CLF appears to be bactericidal in the liver and spl een, which remained negative for M, tuberculosis growth for 2 months. Thus, L-CLF could be useful in the treatment of tuberculosis.