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Parthenolide (PTL), a sesquiterpene lactone, exhibits potent in vitro antischistosomal activity; however, its poor aqueous solubility, low oral bioavailability, and chemical instability may limit its in vivo efficacy. Objective: This study investigated whether nanoencapsulation in nanostructured lipid carriers (NLC) could enable the in vivo antischistosomal activity of PTL. Methods: PTL was isolated from Tanacetum parthenium and incorporated into NLC using hot emulsification followed by ultrasonication. The resulting formulation (NLC-PTL) was physicochemically characterized, and its in vivo antischistosomal efficacy was evaluated in a murine model of Schistosoma mansoni infection. Results: NLC-PTL exhibited nanoscale size, low polydispersity, high encapsulation efficiency, and sustained drug release. In vivo, free PTL showed no significant effect on worm burden, whereas NLC-PTL achieved a marked reduction (77.9%) in adult worms and significantly decreased egg output compared to controls (p &lt; 0.001). Blank NLC had no antiparasitic effect. Conclusions: Nanoencapsulation was associated with in vivo antischistosomal activity of PTL compared to the free compound. These findings suggest that formulation strategies may influence the in vivo performance of lipophilic natural products in schistosomiasis.<\/jats:p>","DOI":"10.3390\/pharmaceutics18060694","type":"journal-article","created":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T18:08:07Z","timestamp":1780510087000},"page":"694","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Nanostructured Lipid Carriers Enable In Vivo Efficacy of Parthenolide in Schistosoma mansoni Infection"],"prefix":"10.3390","volume":"18","author":[{"given":"Jos\u00e9 M\u00e1rcio Fernandes da","family":"Silva","sequence":"first","affiliation":[{"name":"Departamento de Ci\u00eancias Farmac\u00eauticas, Faculdade de Farm\u00e1cia, Universidade Federal de Juiz de Fora, R. Jos\u00e9 Louren\u00e7o Kelmer s\/n, Campus Universit\u00e1rio, Juiz de Fora 36036-900, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominique Mesquita e","family":"Silva","sequence":"additional","affiliation":[{"name":"Departamento de Ci\u00eancias Farmac\u00eauticas, Faculdade de Farm\u00e1cia, Universidade Federal de Juiz de Fora, R. Jos\u00e9 Louren\u00e7o Kelmer s\/n, Campus Universit\u00e1rio, Juiz de Fora 36036-900, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danilo de Souza","family":"Costa","sequence":"additional","affiliation":[{"name":"Departamento de Ci\u00eancias Farmac\u00eauticas, Faculdade de Farm\u00e1cia, Universidade Federal de Juiz de Fora, R. Jos\u00e9 Louren\u00e7o Kelmer s\/n, Campus Universit\u00e1rio, Juiz de Fora 36036-900, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monique C.","family":"Amaro","sequence":"additional","affiliation":[{"name":"N\u00facleo de Pesquisa em Doen\u00e7as Negligenciadas, Universidade Guarulhos, Guarulhos 07023-070, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rayssa A.","family":"Cajas","sequence":"additional","affiliation":[{"name":"N\u00facleo de Pesquisa em Doen\u00e7as Negligenciadas, Universidade Guarulhos, Guarulhos 07023-070, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1766-7031","authenticated-orcid":false,"given":"Josu\u00e9","family":"de Moraes","sequence":"additional","affiliation":[{"name":"N\u00facleo de Pesquisa em Doen\u00e7as Negligenciadas, Universidade Guarulhos, Guarulhos 07023-070, SP, Brazil"},{"name":"N\u00facleo de Pesquisa em Doen\u00e7as Negligenciadas, Instituto Cient\u00edfico e Tecnol\u00f3gico, Universidade Brasil, S\u00e3o Paulo 08230-030, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6276-0994","authenticated-orcid":false,"given":"Guilherme Diniz","family":"Tavares","sequence":"additional","affiliation":[{"name":"Departamento de Ci\u00eancias Farmac\u00eauticas, Faculdade de Farm\u00e1cia, Universidade Federal de Juiz de Fora, R. Jos\u00e9 Louren\u00e7o Kelmer s\/n, Campus Universit\u00e1rio, Juiz de Fora 36036-900, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9096-1336","authenticated-orcid":false,"given":"Ademar Alves","family":"Da Silva Filho","sequence":"additional","affiliation":[{"name":"Departamento de Ci\u00eancias Farmac\u00eauticas, Faculdade de Farm\u00e1cia, Universidade Federal de Juiz de Fora, R. Jos\u00e9 Louren\u00e7o Kelmer s\/n, Campus Universit\u00e1rio, Juiz de Fora 36036-900, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"89","DOI":"10.4155\/fmc-2017-0112","article-title":"Antischistosomal Agents: State of Art and Perspectives","volume":"10","author":"Lago","year":"2018","journal-title":"Future Med. Chem."},{"key":"ref_2","unstructured":"(2026, April 23). Schistosomiasis. 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