Trypanosomatid-Caused Conditions: State of the Art of Therapeutics and Potential Applications of Lipid-Based Nanocarriers

TALEVI, ALAN; MURACA, GIULIANA; BERTI, IGNACIO RIVERO; SBARAGLINI, MARÍA L.; FÁVARO, WAGNER J.; DURÁN, NELSON; CASTRO, GUILLERMO R.

Frontiers in Chemistry

Frontiers

Año: 2020 vol. 8

Trypanosomatid-caused conditions (African trypanosomiasis, Chagas disease,and leishmaniasis) are neglected tropical infectious diseases that mainly affectsocioeconomically vulnerable populations. The available therapeutics display substantiallimitations, among them limited efficacy, safety issues, drug resistance, and, in somecases, inconvenient routes of administration, which made the scenarios with insufficienthealth infrastructure settings inconvenient. Pharmaceutical nanocarriers may providesolutions to some of these obstacles, improving the efficacy?safety balance andtolerability to therapeutic interventions. Here, we overview the state of the art oftherapeutics for trypanosomatid-caused diseases (including approved drugs anddrugs undergoing clinical trials) and the literature on nanolipid pharmaceutical carriersencapsulating approved and non-approved drugs for these diseases. Numerousstudies have focused on the obtention and preclinical assessment of lipid nanocarriers,particularly those addressing the two currently most challenging trypanosomatid-causeddiseases, Chagas disease, and leishmaniasis. In general, in vitro and in vivo studiessuggest that delivering the drugs using such type of nanocarriers could improvethe efficacy?safety balance, diminishing cytotoxicity and organ toxicity, especially inleishmaniasis. This constitutes a very relevant outcome, as it opens the possibility toextended treatment regimens and improved compliance. Despite these advances,last-generation nanosystems, such as targeted nanocarriers and hybrid systems, havestill not been extensively explored in the field of trypanosomatid-caused conditionsand represent promising opportunities for future developments. The potential use ofnanotechnology in extended, well-tolerated drug regimens is particularly interestingin the light of recent descriptions of quiescent/dormant stages of Leishmania andTrypanosoma cruzi, which have been linked to therapeutic failure.