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New antitrypanosomal options are desirable to prevent complications, including a high rate of cardiomyopathy. Recently, a natural substance, lychnopholide, has shown therapeutic potential, especially when encapsulated in biodegradable polymeric nanocapsules. However, little is known regarding possible adverse effects of lychnopholide. Here we show that repeated-dose intravenous administration of free lychnopholide (2.0\u2009mg\/kg\/day) for 20 days caused cardiopathy and mortality in healthy C57BL\/6 mice. Echocardiography revealed concentric left ventricular hypertrophy with preserved ejection fraction, diastolic dysfunction and chamber dilatation at end-stage. Single cardiomyocytes presented altered contractility and Ca<jats:sup>2+<\/jats:sup> handling, with spontaneous Ca<jats:sup>2+<\/jats:sup> waves in diastole. Acute <jats:italic>in vitro<\/jats:italic> lychnopholide application on cardiomyocytes from healthy mice also induced Ca<jats:sup>2+<\/jats:sup> handling alterations with abnormal RyR2-mediated diastolic Ca<jats:sup>2+<\/jats:sup> release. Strikingly, the encapsulation of lychnopholide prevented the cardiac alterations induced <jats:italic>in vivo<\/jats:italic> by the free form repeated doses. Nanocapsules alone had no adverse cardiac effects. Altogether, our data establish lychnopholide presented in nanocapsule form more firmly as a promising new drug candidate to cure Chagas disease with minimal cardiotoxicity. Our study also highlights the potential of nanotechnology not only to improve the efficacy of a drug but also to protect against its adverse effects.<\/jats:p>","DOI":"10.1038\/srep44998","type":"journal-article","created":{"date-parts":[[2017,3,28]],"date-time":"2017-03-28T11:50:09Z","timestamp":1490701809000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["Biodegradable Polymeric Nanocapsules Prevent Cardiotoxicity of Anti-Trypanosomal Lychnopholide"],"prefix":"10.1038","volume":"7","author":[{"given":"Renata Tupinamb\u00e1","family":"Branquinho","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00e9r\u00f4me","family":"Roy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte","family":"Farah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giani Martins","family":"Garcia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franck","family":"Aimond","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Yves","family":"Le Guennec","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D\u00eania Antunes","family":"Saude-Guimar\u00e3es","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Grabe-Guimaraes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanessa Carla Furtado","family":"Mosqueira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"de Lana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvain","family":"Richard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,3,28]]},"reference":[{"key":"BFsrep44998_CR1","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1016\/j.jacc.2013.05.046","volume":"62","author":"MCP Nunes","year":"2013","unstructured":"Nunes, M. 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