{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T06:38:12Z","timestamp":1789195092952,"version":"build-2803163510"},"reference-count":51,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T00:00:00Z","timestamp":1769558400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministerio de Ciencia, Innovaci\u00f3n y Universidades","award":["PID2023-147765OB-C21"],"award-info":[{"award-number":["PID2023-147765OB-C21"]}]},{"name":"Ministerio de Ciencia, Innovaci\u00f3n y Universidades","award":["PID2023-147765OB-C22"],"award-info":[{"award-number":["PID2023-147765OB-C22"]}]},{"name":"Fundaci\u00f3n Roviralta","award":["Chair \u201cMaria Francisca de Roviralta of Molecular Parasitology, Leishmaniasis and One Health\u201d"],"award-info":[{"award-number":["Chair \u201cMaria Francisca de Roviralta of Molecular Parasitology, Leishmaniasis and One Health\u201d"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Cutaneous leishmaniasis (CL) is a neglected tropical disease for which current chemotherapeutic options are limited by systemic toxicity (such as hepato-nephrotoxicity, arrhythmia, nausea, vomiting) and difficult administration regimens. Pentamidine (PTM), although effective, exhibits severe dose-limiting adverse effects. Polymeric micelles based on Pluronic\u00ae F127 (F127) offer an attractive strategy to improve PTM delivery by enhancing solubility, reducing cytotoxicity, and enabling controlled release. Here, we developed PTM-loaded F127 polymeric micelles and performed a multidisciplinary evaluation combining physicochemical characterization, in vitro biological assays, and gene expression profiling. Dynamic light scattering, UV\u2013visible absorption, fluorescence spectroscopy, and NMR confirmed micelle formation, PTM\u2013polymer interactions, and temperature-dependent assembly. PTM-loaded micelles exhibited biorelevant nanoscale dimensions and preserved stability under physiological conditions. Biological assays demonstrated that F127 micelles markedly reduced PTM cytotoxicity in RAW264.7 macrophages while maintaining potent antileishmanial activity against Leishmania major promastigotes. RT-qPCR analysis revealed modulation of key pathways involved in redox homeostasis, oxidative stress, calcium regulation, apoptosis-like responses, and drug resistance, suggesting that micellar encapsulation influences both PTM bioavailability and parasite stress responses. Overall, PTM-loaded F127 micelles significantly improved the therapeutic index of PTM in vitro. These findings support the potential of F127 polymeric micelles as a promising nanocarrier platform for safer and more effective CL therapy.<\/jats:p>","DOI":"10.3390\/ijms27031300","type":"journal-article","created":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T15:04:46Z","timestamp":1769612686000},"page":"1300","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Pluronic\u00ae F127 Polymeric Micelles as Nanocarriers for Pentamidine: Improving Safety and Biological Efficacy Against Leishmania major"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6631-6767","authenticated-orcid":false,"given":"Kristell Panta","family":"Quezada","sequence":"first","affiliation":[{"name":"Department of Microbiology and Parasitology, Navarra Institute for Health Research (IdisNA), University of Navarra, 31080 Pamplona, Spain"},{"name":"Department of Chemistry, School of Science, University of Navarra, 31080 Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1477-6710","authenticated-orcid":false,"given":"Gustavo","family":"Gonz\u00e1lez-Gaitano","sequence":"additional","affiliation":[{"name":"Department of Chemistry, School of Science, University of Navarra, 31080 Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2193-7316","authenticated-orcid":false,"given":"Paul","family":"Nguewa","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Parasitology, Navarra Institute for Health Research (IdisNA), University of Navarra, 31080 Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e202","DOI":"10.1093\/cid\/ciw670","article-title":"Diagnosis and Treatment of Leishmaniasis: Clinical Practice Guidelines by the Infectious Diseases Society of America (IDSA) and the American Society of Tropical Medicine and Hygiene (ASTMH)","volume":"63","author":"Aronson","year":"2016","journal-title":"Clin. 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