Engineering oral and parenteral amorphous amphotericin B formulations against experimental trypanosoma cruzi infections

Chagas disease (CD) is a parasitic zoonosis endemic in most mainland countries of central and South America affecting nearly 10 million people amongst 100 million people that are at high risk. Treatment is only effective if applied at early stages of the disease. Only two drugs (benznidazole and nifurtimox) have so far been marketed and both share various limitations such as variable efficacy, many side effects and long lasting treatments thus reducing compliance. Polyaggregated amphotericin B - albumin microspheres (AmB-AME) and dimeric AmB - sodium deoxycholate micelles (AmB-NaDC) exhibited a promising selectivity index (SI) (>175) with lower IC50 values against epimastigotes than those obtained for licensed drugs (18-30-fold and 7-12 fold compared to benznidazole and nifurtimox respectively depending on the parasite strain). AmB-AME but not AmB-NaDC reduced significantly the parasitaemia levels (3.6-fold) in comparison to the control group after parenteral administration at day 7 post-infection. However, the oral administration of AmB-NaDC (10-15 mg/kg/day for 10 days) resulted in 75 % reduction of parasitaemia levels as compared to parenterally administered AmB-AME, thus presented results illustrate for the first time oral efficacy of AmB in the treatment of trypanosomiasis. AmB-NaDC is an easily scalable, affordable formulation prepared from GRAS excipientsenabling treatment access worldwide and therefore it can be regarded as a promising therapy for trypanosomiasis.