Trypanosoma cruzi: Does the intake of nanoencapsulated benznidazole control acute infections?

Trypanosoma cruzi is a hemoflagellate protozoan that causes Chagas Disease (CD), a neglected disease first described in 1909 (Chagas 1909). The World Health Organization estimated that eight million people are infected worldwide, leading to 12,500 deaths per year, mainly in Latin America (WHO 2021). The route of infection is via insect vectors from the Triatominae subfamily (Order: Hemiptera, Family: Reduviidae), blood transfusions, accidents, oral infections, and congenital transmission (Carlier and Truyens 2010; WHO - Chagas Disease, 2018; Fracasso et al., 2021).

CD is often asymptomatic. However, specific symptoms such asmyalgias and fever may occur in the acute phase of the disease. Following the acute phase, CD progresses to the chronic phase and may remain asymptomatic for years or be characterized by cardiac, digestive, and/or neurological pathologies that may lead to systemic and pulmonary embolisms and, in the most severe cases, sudden death (Rassi et al., 2017; Pérez-Molina and Molina, 2018).

There are currently two drugs to control CD: Benznidazole (BNZ), a first-choice drug for treating the disease, and Nifurtimox, the second-line option to benznidazole. However, the Brazilian Health Regulatory Agency (ANVISA) only clears benznidazole for drug treatment in Brazil. According to the BNZ package insert, numerous side effects of the drug have been reported, such as skin reactions, nausea, tingling or nerve inflammation symptoms, headaches, vertigo, fatigue, and changes in blood, besides relative time treatments (Ádley et al., 2011; Apt 2017; WHO 2021).

In addition to the aforementioned side effects, another point that hinders the treatment is the dosage of the drug. Currently, it is marketed by the Pharmaceutical Laboratory of the State of Pernambuco (LAFEPE) in two 100 mg or 12.5 mg formulations, making treatment difficult in children, for example, for whom the dose is 5 mg/kg of body weight to 10 mg/kg for sixty consecutive days according to the manufacturer's recommendations. Thus, the efficacy of the drug therapy declines with the duration of the infection and is still a matter of debate in the late chronic phase of CD (Pérez-Molina and Molina, 2018; Who 2007; Conitec 2018).

Nanoparticulate drug delivery systems have emerged as a promising area of research in the therapy and prevention of neglected tropical diseases such as CD. These delivery systems provide novel mechanisms for targeted drug delivery within the host, maximizing therapeutic effects while minimizing systemic side effects (Volpedo et al., 2019). However, as the study of nanocapsules is increasing, we find several types of nanocapsules.

Several studies have characterized encapsulated formulations of natural compounds or drugs. Jaguezeski et al. (2019) showed that the use of Eudragit® nanocapsules potentiates the compound actions at doses ten times smaller than the usual dose. Vinuesa et al. examined the efficacy of a novel BZN-carrier nanostructure in fibroblasts in vitro and in vivo murine models, finding reduced mammalian cell cytotoxicity, decreased parasite viability, and increased infected mice survival rates (Vinuesa et al., 2017). Similarly, lychnopholide encapsulated in polymeric nanocapsules has been shown to be effective in T. cruzi infections and just as effective as the standard BZN treatment during the acute phase via intravenous administration in murine models (Branquinho et al., 2014). This study aimed to characterize BNZ Eudragit nanocapsules and evaluate their efficacy in an acute infection by the Y strain of Trypanosoma cruzi in female Swiss mice.

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