Prophylactic role of liposomized chloroquine against murine cryptococcosis less susceptible to fluconazole.

Abstract

PURPOSE: The prophylactic role of liposomized chloroquine (lip-CQ) has been assessed against less susceptible Cryptococcus neoformans infection in murine model. METHODS: In the current study, we investigated the antifungal activity of lip-CQ against C. neoformans in macrophages cell line (J 774) and murine model. Mice were pretreated with free as well as liposomized formulations of CQ at various doses. The anticryptococcal activity of fluconazole was compared in mice with or without CQ pretreatment. The efficacy of CQ prophylaxis was assessed by survival as well as colony forming units (cfu) in brain and lungs of treated mice. RESULTS: Fluconazole alone was not found significantly effective against C. neoformans in both in vitro and in vivo studies. However, the antifungal activity of fluconazole increases in chloroquine-pretreated mice. Lip-CQ was found to be more effective in comparison to the same dose of free chloroquine in reducing fungal burden from macrophages in vitro and lungs and brain of C. neoformans infected mice. CONCLUSIONS: The enhanced prophylactic activity of lip-CQ seems due to rapid uptake of drug-containing liposomes by macrophages. The liposome-mediated accumulation of CQ in macrophages makes the environment unfavorable (alkaline) for the intracellular multiplication of C. neoformans. Moreover, the increased incidence of multi-drug resistance and diversity of pathogenic microorganisms inhibited or killed by CQ makes it the drug of choice for prophylactic therapy.