{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T23:40:57Z","timestamp":1771630857306,"version":"3.50.1"},"reference-count":44,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2025,3,21]],"date-time":"2025-03-21T00:00:00Z","timestamp":1742515200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"FAPERJ Carlos Chagas Filho Foundation for Research Support of the State of Rio de Janeiro (FAPERJ)","award":["E-26\/201.384\/2022"],"award-info":[{"award-number":["E-26\/201.384\/2022"]}]},{"name":"FAPERJ Carlos Chagas Filho Foundation for Research Support of the State of Rio de Janeiro (FAPERJ)","award":["E26\/010.002426\/2019"],"award-info":[{"award-number":["E26\/010.002426\/2019"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background\/Objectives: Cutaneous leishmaniasis (CL) is a vector-borne neglected disease that can cause permanent deformities. Current chemotherapy based on injections with toxic drugs or oral miltefosine poses many drawbacks, urging the need for new oral therapies. Here, we proposed to increase the bioavailability of NAT22, an intralesionally but not orally active antileishmanial chalcone, through nanocrystallization to promote its oral use in CL. Methods\/Results: NAT22 nanocrystals were produced using a solvent-free green process of dry and wet milling that reduced NAT22 crystal sizes by around 1500-fold to 257 nm (nanoNAT22). Such reduction in size increased water solubility by 15-fold to 4.3 \u00b5g\/mL and ensured stability in the absence of stabilizers for at least one month. Of note, nanoNAT22 in aqueous medium was more selective for parasites (SI = 35.2) than NAT22 in 1% DMSO (SI = 7.6). Leishmania amazonensis-infected mice treated with oral nanoNAT22 had lesion sizes and parasite loads similar to those achieved with intralesional Glucantime\u00ae, and significantly smaller than NAT22. Conclusions: Together, these results indicate that nanocrystallization is an effective process to render NAT22 chalcone also orally active against CL.<\/jats:p>","DOI":"10.3390\/pharmaceutics17040399","type":"journal-article","created":{"date-parts":[[2025,3,21]],"date-time":"2025-03-21T10:10:08Z","timestamp":1742551808000},"page":"399","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Nanocrystallization Effectively Improves the Oral Efficacy of an Antileishmanial Chalcone"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9440-5292","authenticated-orcid":false,"given":"Maria Paula Gon\u00e7alves","family":"Borsodi","sequence":"first","affiliation":[{"name":"Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro 21941-902, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wallace","family":"Pacienza-Lima","sequence":"additional","affiliation":[{"name":"Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro 21941-902, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jaqueline Correia Villa\u00e7a","family":"Menezes","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Federal University of Rio de Janeiro, Rio de Janeiro 21941-902, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4872-8960","authenticated-orcid":false,"given":"Douglas","family":"Escrivani-Oliveira","sequence":"additional","affiliation":[{"name":"Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro 21941-902, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natalia","family":"Arruda-Costa","sequence":"additional","affiliation":[{"name":"Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro 21941-902, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alcides Jos\u00e9 Monteiro da","family":"Silva","sequence":"additional","affiliation":[{"name":"Institute of Natural Products Research, Federal University of Rio de Janeiro, Rio de Janeiro 21941-902, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lucio Mendes","family":"Cabral","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Federal University of Rio de Janeiro, Rio de Janeiro 21941-902, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2493-5826","authenticated-orcid":false,"given":"Patrick G.","family":"Steel","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Durham University, Lower Mountjoy, South Rd, Durham DH1 3LE, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1642-6669","authenticated-orcid":false,"given":"Ariane de Jesus","family":"Sousa-Batista","sequence":"additional","affiliation":[{"name":"Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro 21941-902, Brazil"},{"name":"Nanotechnology Engineering Program, Alberto Luiz Coimbra Institute for Graduate Studies, and Research in Engineering\u2014COPPE, Federal University of Rio de Janeiro, Rio de Janeiro 21941-972, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bartira","family":"Rossi-Bergmann","sequence":"additional","affiliation":[{"name":"Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro 21941-902, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1007\/s44197-024-00190-z","article-title":"Global Dilemma and Needs Assessment Toward Achieving Sustainable Development Goals in Controlling Leishmaniasis","volume":"14","author":"Bamorovat","year":"2024","journal-title":"J. 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