Cure of experimental Chagas' disease by the bis-triazole DO870 incorporated into 'stealth' polyethyleneglycol-polylactide nanospheres

Molina, Judith; Urbina, Julio A.; Gref, Ruxandra; Brener, Z.; Júnior, José Maciel Rodrigues

doi:10.1093/jac/47.1.101

Cited by 48 publications

(29 citation statements)

References 9 publications

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“…The efficacy of this strategy appears to be superior to or possibly comparable to the efficacy of chemotherapy, and the strategy has the major advantage of requiring only two doses, whereas drug treatments rely on daily doses for a prolonged time (29,47). The treatment described here may thus represent a promising alternative for Chagas' disease therapy, alone or in combination with other drug treatments.…”

Section: Discussionmentioning

confidence: 95%

Immunotherapy ofTrypanosoma cruziInfection with DNA Vaccines in Mice

et al. 2004

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The mechanisms involved in the pathology of chronic chagasic cardiomyopathy are still debated, and the controversy has interfered with the development of new treatments and vaccines. Because of the potential of DNA vaccines for immunotherapy of chronic and infectious diseases, we tested if DNA vaccines could control an ongoing Trypanosoma cruzi infection. BALB/c mice were infected with a lethal dose (5 ؋ 10 4 parasites) as a model of acute infection, and then they were treated with two injections of 100 g of plasmid DNA 1 week apart, beginning on day 5 postinfection. Control mice had high levels of parasitemia and mortality and severe cardiac inflammation, while mice treated with plasmid DNA encoding trypomastigote surface antigen 1 or Tc24 had reduced parasitemia and mild cardiac inflammation and >70% survived the infection. The efficacy of the immunotherapy also was significant when it was delayed until days 10 and 15 after infection. Parasitological analysis of cardiac tissue of surviving mice indicated that most mice still contained detectable parasite kinetoplast DNA but fewer mice contained live parasites, suggesting that there was efficient but not complete parasite elimination. DNA vaccine immunotherapy was also evaluated in CD1 mice infected with a low dose (5 ؋ 10 2 parasites) as a model of chronic infection. Immunotherapy was initiated on day 70 postinfection and resulted in improved survival and reduced cardiac tissue inflammation. These results suggest that DNA vaccines have strong potential for the immunotherapy of T. cruzi infection and may provide new alternatives for the control of Chagas' disease.

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Section: Discussionmentioning

confidence: 95%

Immunotherapy ofTrypanosoma cruziInfection with DNA Vaccines in Mice

et al. 2004

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“…In general, the results with these drugs were contradictory or even unsatisfactory (7,35,36). In an attempt to overcome the limitations of CD therapy, some researchers recently suggested the development of drug delivery systems using nanocarriers to improve the drug pharmacological effects (35,37) by controlling drug release, reducing toxicity, and modulating the pharmacokinetics and biodistribution (8,35,37,38).…”

Section: Discussionmentioning

confidence: 99%

Efficacy of Lychnopholide Polymeric Nanocapsules after Oral and Intravenous Administration in Murine Experimental Chagas Disease

Mello

Branquinho

Oliveira

et al. 2016

Antimicrob Agents Chemother

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The etiological treatment of Chagas disease remains neglected. The compounds available show several limitations, mainly during the chronic phase. Lychnopholide encapsulated in polymeric nanocapsules (LYC-NC) was efficacious in mice infected with Trypanosoma cruzi and treated by intravenous administration during the acute phase (AP). As the oral route is preferred for treatment of chronic infections, such as Chagas disease, this study evaluated the use of oral LYC-NC in the AP and also compared it with LYC-NC administered to mice by the oral and intravenous routes during the chronic phase (CP). The therapeutic efficacy was evaluated by fresh blood examination, hemoculture, PCR, and enzyme-linked immunosorbent assay (ELISA). The cure rates in the AP and CP were 62.5% and 55.6%, respectively, upon oral administration of LYC-poly(D,L-lactide)-polyethylene glycol nanocapsules (LYC-PLA-PEG-NC) and 57.0% and 30.0%, respectively, with LYC-poly--caprolactone nanocapsules (LYC-PCL-NC). These cure rates were significantly higher than that of free LYC, which did not cure any animals. LYC-NC formulations administered orally during the AP showed cure rates similar to that of benznidazole, but only LYC-NC cured mice in the CP. Similar results were achieved with intravenous treatment during 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. This work is the first report of cure of experimental Chagas disease via oral administration during the CP. These findings represent a new and important perspective for oral treatment of Chagas disease.

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“…Among these are allopurinol, an antiuricemic hypoxanthine that is used to treat gout, and antifungals that inhibit ergosterol, such as ketoconazole, itraconazole and fluconazole [42][43][44][45][46] . These have not been shown to be effective in vivo, including during the acute phase of the disease.…”

Section: Drugs In Use and New Strategies For Treating Chagas Diseasementioning

confidence: 99%

Chagas disease: What is known and what should be improved: a systemic review

Coura

Borges-Pereira

2012

Rev. Soc. Bras. Med. Trop.

118

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This study consists of a broad review on what is known and what should be improved regarding knowledge of Chagas disease, not only through analysis on the main studies published on the topics discussed, but to a large extent based on experience of this subject, acquired over the past 50 years (1961-2011). Among the subjects covered, we highlight the pathogenesis and evolution of infection by Trypanosoma cruzi, drugs in use and new strategies for treating Chagas disease; the serological tests for the diagnosis and the controls of cure the infection; the regional variations in prevalence, morbidity and response to treatment of the disease; the importance of metacyclogenesis of T. cruzi in different species of triatomines and its capacity to transmit Chagas infection; the risks of adaptation of wild triatomines to human dwellings; the morbidity and need for a surveillance and control program for Chagas disease in the Amazon region and the need to prioritize initiatives for controlling Chagas disease in Latin America and Mexico and in non-endemic countries, which is today a major international dilemma. Finally, we raise the need for to create a new initiative for controlling Chagas disease in the Gran Chaco, which involves parts of Argentina, Bolivia and Paraguay.

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Cure of experimental Chagas' disease by the bis-triazole DO870 incorporated into 'stealth' polyethyleneglycol-polylactide nanospheres

Cited by 48 publications

References 9 publications

Immunotherapy ofTrypanosoma cruziInfection with DNA Vaccines in Mice

Immunotherapy ofTrypanosoma cruziInfection with DNA Vaccines in Mice

Efficacy of Lychnopholide Polymeric Nanocapsules after Oral and Intravenous Administration in Murine Experimental Chagas Disease

Chagas disease: What is known and what should be improved: a systemic review

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