Oral Nanocapsule Treatment Cures Mice with Chronic Phase Chagas Disease

Oral treatment with nanocapsules containing the Brazilian plant extract lychnopholide was shown to eradicate Trypanosoma cruzi in both the acute and chronic phases of Chagas disease.

Conventional drugs such as benznidazole and nifurtimox are effective in controlling the parasite during the acute phase of the disease but lose their potency during the chronic phase.

Investigators at the Federal University of Ouro Preto (Minas Gerais, Brazil) had previously shown the value of lychnopholide (LYC) - when encapsulated in polymeric nanocapsules (LYC-NC) - for treating mice infected with T. cruzi by intravenous administration during the acute phase (AP). As the oral route is preferred for treatment of chronic infections such as Chagas disease, they evaluated the use of oral LYC-NC in the AP, and also compared it to oral and intravenous treatment in the chronic phase (CP) in mice. The therapeutic efficacy was evaluated by fresh blood examination, hemoculture, PCR, and ELISA.

Results published in the June 20, 2016, online edition of the journal Antimicrobial Agents and Chemotherapy revealed that cure rates in the AP and CP were 62.5% and 55.6%, respectively, upon oral administration of LYC-PLA (polylactic acid)-PEG (polyethylene glycol)-NC, and 57.0% and 30.0%, respectively, with LYC-PCL (phosphatidyl choline)-NC. These cure rates were significantly higher than free-LYC, which did not cure any animals. LYC-NC formulations administered orally during the AP showed similar cure rates to benznidazole, but only LYC-NC cured mice in the CP.

The higher cure rates obtained with LYC loaded in PLA-PEG-NC may be due to the smaller particle size of these NC and the presence of PEG, which influence tissue diffusion and the controlled release of LYC. Furthermore, PLA-PEG-NC may improve the stability of the drug in the gastrointestinal tract.

"Both nanoencapsulated formulations are so simple that they may be produced in a simple laboratory," said senior author Dr. Marta de Lana, professor of clinical parasitology at the Federal University of Ouro Preto. "Additionally, scale-up for commercial production would be simple."

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Federal University of Ouro Preto