Albaconazole Polymeric Nanocapsules for Treating Trypanosoma cruzi Infections

The therapeutic management of Chagas disease requires new medicines because the standard-of-care drugs available induce adverse effects and have limited efficacy. In this study, we developed a formulation of albaconazole (ABZ) loaded in biodegradable polymeric nanocapsules (NCs). Free ABZ and ABZ-loaded NCs were similarly active against the Y strain and inactive against the Colombian strain epimastigotes of Trypanosoma cruzi. Infected mice were given ABZ in different doses and treatment schedules by oral, SC, and IM routes during the acute phase of infection. Free ABZ taken orally reduced parasitemia and suppressed mortality; however, all the animals maintained patent parasitemia during and after treatment. ABZ-NCs increased anti-T. cruzi effects (p < 0.05), inducing negative parasitemia during treatment in most of the tested regimens. The parasitemia level was also significantly reduced after treatment with ABZ-NCs during the acute phase of the disease, and relapses were delayed compared with the free ABZ treatment. Once- and twice-daily doses were similarly effective, demonstrating that the NCs prolonged the ABZ-NC residence time. Free ABZ and ABZ-NCs did not prevent infection, ABZ seemed to have suppressive effects on T. cruzi growth, and encapsulation prolonged this suppression. The analysis of the in vivo results indicated that the NCs significantly improved the safety of ABZ in the mouse model, suggesting that the increased ABZ-NC dosage regimen merits further efficacy and pharmacokinetic evaluations.