From Benznidazole to New Drugs: Nanotechnology Contribution in Chagas Disease

Abstract

Chagas disease is a neglected tropical disease caused by the protozoan Trypanosoma cruzi. Benznidazole and nifurtimox are the two approved drugs for their treatment, but both drugs present side effects and efficacy problems, especially in the chronic phase of this disease. Therefore, new molecules have been tested with promising results aiming for strategic targeting action against T. cruzi. Several studies involve in vitro screening, but a considerable number of in vivo studies describe drug bioavailability increment, drug stability, toxicity assessment, and mainly the efficacy of new drugs and formulations. In this context, new drug delivery systems, such as nanotechnology systems, have been developed for these purposes. Some nanocarriers are able to interact with the immune system of the vertebrate host, modulating the immune response to the elimination of pathogenic microorganisms. In this overview of nanotechnology-based delivery strategies for established and new antichagasic agents, different strategies, and limitations of a wide class of nanocarriers are explored, as new perspectives in the treatment and monitoring of Chagas disease.

The End Justifies the Means: Chagas Disease from a Perspective of the Host–Trypanosoma cruzi Interaction

“…There are other limitations of these medications, like strong side effects that lead to the interruption of the treatment [96]. Despite being discovered 115 years ago, the disease has no effective treatment in the chronic phase, highlighting the fact that CD is a neglected disease facing multiple political, economic, and cultural barriers that influences its scientific research [163]. Therefore, the development of new drugs for the treatment of CD requires strong support, although the lack of investment does not prevent researchers in concentrating their efforts to improve the solubility and bioavailability of current medicines, or to search for new therapeutic compounds [164,165].…”

Chagas Disease across the Ages: A Historical View and Commentary on Navigating Future Challenges

“…In addition, the development of drug resistance, in conjunction with the fact that Nifurtimox and Benznidazole are considered as “obsolete” urge the development of new alternative [ 20 ]. New therapeutic options involving new or repurposed drugs [ 21 , 22 , 23 ] are urgently needed. Fexinidazole is undergoing clinical trials for the treatment of (NCT03587766), and the oxaborole DNDI-6148 has been nominated as a clinical candidate for the treatment of Chagas disease and is in phase I clinical trials (EudraCT 2018-004023-37) [ 24 ].…”

Nanomedicines against Chagas disease: a critical review

“…Nanomedicines are used to solve the problems posed by poor solubility and/or permeability and high toxicity of drugs with low molecular weight [ 1 – 2 ]. Different 2-nitroimidazole-based nanomedicines against Chagas disease (CD) to reduce the toxicity and increase the effectiveness of benznidazole (BNZ) treatment have been preclinically screened in the last two decades (see the recently reviewed BNZ-based preclinical anti-CD nanomedicines [ 3 ]). But how realistic is thinking of nanomedicines to treat CD?…”