Effective Treatment of Acute and Chronic Murine Tuberculosis with Liposome-Encapsulated Clofazimine

Abstract

The therapeutic efficacy of liposomal clofazimine (L-CLF) was studied in mice infected with Mycobacterium tuberculosisErdman. Groups of mice were treated 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 ofM. tuberculosis in the spleen, liver, and lungs were determined. F-CLF at the maximum tolerated dose of 5 mg/kg of body weight was ineffective; however, 10-fold-higher doses of L-CLF demonstrated a dose response with significant CFU reduction in all tissues without any toxic effects. 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 showed 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. tuberculosisin all three tissues. L-CLF appears to be bactericidal in the liver and spleen, which remained negative for M. tuberculosis growth for 2 months. Thus, L-CLF could be useful in the treatment of tuberculosis.

Liposome-Nanogel Structures for Future Pharmaceutical Applications

“…In particular, liposomes have been used as carriers for many kinds of molecules such as anti-cancer [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25], antibacterial [26][27][28][29], anti-fungal [30,31] and anti-viral [32,33] agents, and bioactive macromolecules [34][35][36][37][38][39].…”

Evaluation of Drug Targeting Strategies and Liposomal Trafficking

“…The administration of liposomal retinoids is expected to induce differentiation of tumor cells [28]. Liposomes encapsulating anti-bacterial agents, such as amikacin [29,30] and clofazimine [31], anti-fungal agents [32,33] and anti-viral agents [34,35] are used for treatment of infectious diseases.…”

Use of liposomized tetracycline in elimination ofWolbachiaendobacterium of human lymphatic filariidBrugia malayiin a rodent model

“…However, successful treatment requires administration of the drug for a longer duration that is not feasible in filaria endemic areas (Hoerauf et al 2000). Research is therefore needed for a targeted killing of Wolbachia that could be made possible with better absorption and retention of the drug at the site of predilection thus reducing the dosage and treatment duration (Adams et al 1999).…”