{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T15:05:51Z","timestamp":1772982351434,"version":"3.50.1"},"reference-count":57,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2022,12,15]],"date-time":"2022-12-15T00:00:00Z","timestamp":1671062400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"FAPEMIG, and the Brazilian Program for Malaria Control (MS, Brazil)","award":["#00007-14"],"award-info":[{"award-number":["#00007-14"]}]},{"name":"FAPEMIG, and the Brazilian Program for Malaria Control (MS, Brazil)","award":["#40\/11"],"award-info":[{"award-number":["#40\/11"]}]},{"name":"FAPEMIG, and the Brazilian Program for Malaria Control (MS, Brazil)","award":["#768\/13"],"award-info":[{"award-number":["#768\/13"]}]},{"name":"FAPEMIG, and the Brazilian Program for Malaria Control (MS, Brazil)","award":["978\/20"],"award-info":[{"award-number":["978\/20"]}]},{"name":"bilateral CAPES-COFECUB Research Collaboration between Brazil and France","award":["#00007-14"],"award-info":[{"award-number":["#00007-14"]}]},{"name":"bilateral CAPES-COFECUB Research Collaboration between Brazil and France","award":["#40\/11"],"award-info":[{"award-number":["#40\/11"]}]},{"name":"bilateral CAPES-COFECUB Research Collaboration between Brazil and France","award":["#768\/13"],"award-info":[{"award-number":["#768\/13"]}]},{"name":"bilateral CAPES-COFECUB Research Collaboration between Brazil and France","award":["978\/20"],"award-info":[{"award-number":["978\/20"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Polymers"],"abstract":"<jats:p>Artemether (ATM) is an effective antimalarial drug that also has a short half-life in the blood. Furthermore, ATM is also cardiotoxic and is associated with pro-arrhythmogenic risks. We aimed to develop a delivery system enabling the prolonged release of ATM into the blood coupled with reduced cardiotoxicity. To achieve this, we prepared polymeric nanocapsules (NCs) from different biodegradable polyesters, namely poly(D,L-lactide) (PLA), poly-\u03b5-caprolactone (PCL), and surface-modified NCs, using a monomethoxi-polyethylene glycol-block-poly(D,L-lactide) (PEG5kDa-PLA45kDa) polymer. Using this approach, we were able to encapsulate high yields of ATM (&gt;85%, 0\u20134 mg\/mL) within the oily core of the NCs. The PCL-NCs exhibited the highest percentage of ATM loading as well as a slow release rate. Atomic force microscopy showed nanometric and spherical particles with a narrow size dispersion. We used the PCL NCs loaded with ATM for biological evaluation following IV administration. As with free-ATM, the ATM-PCL-NCs formulation exhibited potent antimalarial efficacy using either the \u201cFour-day test\u201d protocol (ATM total at the end of the 4 daily doses: 40 and 80 mg\/kg) in Swiss mice infected with P. berghei or a single low dose (20 mg\/kg) of ATM in mice with higher parasitemia (15%). In healthy rats, IV administration of single doses of free-ATM (40 or 80 mg\/kg) prolonged cardiac QT and QTc intervals and induced both bradycardia and hypotension. Repeated IV administration of free-ATM (four IV doses at 20 mg\/kg every 12 h for 48 h) also prolonged the QT and QTc intervals but, paradoxically, induced tachycardia and hypertension. Remarkably, the incorporation of ATM in ATM-PCL-NCs reduced all adverse effects. In conclusion, the encapsulation of ATM in biodegradable polyester NCs reduces its cardiovascular toxicity without affecting its antimalarial efficacy.<\/jats:p>","DOI":"10.3390\/polym14245503","type":"journal-article","created":{"date-parts":[[2022,12,16]],"date-time":"2022-12-16T02:54:02Z","timestamp":1671159242000},"page":"5503","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Polyester Nanocapsules for Intravenous Delivery of Artemether: Formulation Development, Antimalarial Efficacy, and Cardioprotective Effects In Vivo"],"prefix":"10.3390","volume":"14","author":[{"given":"Alessandra Teixeira","family":"Vidal-Diniz","sequence":"first","affiliation":[{"name":"School of Pharmacy, Universidade Federal de Ouro Preto (UFOP), Campus Universit\u00e1rio Morro do Cruzeiro, Ouro Preto 35400-000, MG, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Homero Nogueira","family":"Guimar\u00e3es","sequence":"additional","affiliation":[{"name":"Department of Electrical Engineering, Federal University of Minas Gerais, Belo Horizonte 31270-901, MG, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giani Martins","family":"Garcia","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Universidade Federal de Ouro Preto (UFOP), Campus Universit\u00e1rio Morro do Cruzeiro, Ouro Preto 35400-000, MG, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5550-7157","authenticated-orcid":false,"given":"\u00c9rika Martins","family":"Braga","sequence":"additional","affiliation":[{"name":"Department of Parasitology, Institute of Biological Sciences, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte 31270-901, MG, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9460-6705","authenticated-orcid":false,"given":"Sylvain","family":"Richard","sequence":"additional","affiliation":[{"name":"CNRS, INSERM, Universit\u00e9 de Montpellier, 34295 Montpellier, France"},{"name":"PhyMedExp, CHU Arnaud de Villeneuve 371, Avenue du Doyen Gaston Giraud, CEDEX 05, 34295 Montpellier, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6503-5314","authenticated-orcid":false,"given":"Andrea","family":"Grabe-Guimar\u00e3es","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Universidade Federal de Ouro Preto (UFOP), Campus Universit\u00e1rio Morro do Cruzeiro, Ouro Preto 35400-000, MG, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0368-6090","authenticated-orcid":false,"given":"Vanessa Carla Furtado","family":"Mosqueira","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Universidade Federal de Ouro Preto (UFOP), Campus Universit\u00e1rio Morro do Cruzeiro, Ouro Preto 35400-000, MG, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,15]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2022, November 22). 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