{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T09:36:01Z","timestamp":1786700161761,"version":"build-2736575974"},"reference-count":74,"publisher":"Wiley","issue":"30","license":[{"start":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T00:00:00Z","timestamp":1783296000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T00:00:00Z","timestamp":1783296000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"publisher","award":["COMPETE2030\u2010FEDER\u201000735300"],"award-info":[{"award-number":["COMPETE2030\u2010FEDER\u201000735300"]}],"id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Adv Healthcare Materials"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Cutaneous leishmaniasis (CL) remains difficult to treat because\n                    <jats:italic>Leishmania<\/jats:italic>\n                    parasites persist within dermal macrophages and suppress their microbicidal activity, promoting chronic infection. Toll\u2010like receptor (TLR) agonists can restore macrophage effector functions, but their therapeutic use is limited by systemic toxicity. Here, we developed a lipid\u2010based nanoemulsion (NE) for the systemic delivery of the TLR7 agonist gardiquimod (GDQM) to improve macrophage targeting and reduce off\u2010target inflammatory effects. Following intravenous administration, GDQM\u2010NEs efficiently accumulated in dermal lesions and significantly reduced systemic cytokine release compared with free GDQM, resulting in an improved safety profile. Importantly, nanoencapsulation preserved GDQM antileishmanial activity achieving an approximately 2\u2010log reduction in parasite burden. Treatment induced both Th1\u2010associated cytokines (IFN\u2010\u03b3 and IL\u201012p70) and regulatory responses, including IL\u201010 production and FoxP3\n                    <jats:sup>+<\/jats:sup>\n                    regulatory T\u2010cell expansion. Despite efficient lesion accumulation, CD86 upregulation was detected in macrophages from draining lymph nodes (dLNs) but not at the lesion site, indicating limited local macrophage activation. These findings indicate that GDQM\u2010NEs effectively overcome major delivery and safety barriers associated with systemic TLR7 agonist administration, whereas the lesion microenvironment and TLR\u2010driven regulatory mechanisms remain key constraints on therapeutic efficacy. Combining TLR agonists with strategies that counteract these local suppressive pathways may further enhance treatment outcomes in CL.\n                  <\/jats:p>","DOI":"10.1002\/adhm.71415","type":"journal-article","created":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T05:24:46Z","timestamp":1783401886000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Gardiquimod Nanoemulsion Targets Cutaneous Leishmaniasis Lesions Reducing Systemic Toxicity and Parasite Burden"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5523-4758","authenticated-orcid":false,"given":"Carmen","family":"Palomino\u2010Cano","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences School of Pharmacy and Nutrition University of Navarra  Pamplona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Carmen","family":"Mera\u2010Delgado","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences School of Pharmacy and Nutrition University of Navarra  Pamplona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esther","family":"Moreno","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences School of Pharmacy and Nutrition University of Navarra  Pamplona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esther","family":"Larrea","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology. School of Sciences University of Navarra  Pamplona Spain"},{"name":"Institute For Health Research (IdiSNA)  Pamplona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lecnia","family":"Aguirre","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences School of Pharmacy and Nutrition University of Navarra  Pamplona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan Miguel","family":"Zanatta","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Sciences University of S\u00e3o Paulo  S\u00e3o Paulo Brazil"},{"name":"Life and Health Sciences Research Institute (ICVS) School of Medicine University of Minho  Braga Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00f3nia","family":"Barros\u2010Carvalho","sequence":"additional","affiliation":[{"name":"Life and Health Sciences Research Institute (ICVS) School of Medicine University of Minho  Braga Portugal"},{"name":"ICVS\/3B's\u2010PT Government Associate Laboratory  Braga\/Guimar\u00e3es Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iola F.","family":"Duarte","sequence":"additional","affiliation":[{"name":"LAQV\u2010REQUIMTE Department of Chemistry University of Aveiro  Aveiro Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9270-2717","authenticated-orcid":false,"given":"Ricardo","family":"Silvestre","sequence":"additional","affiliation":[{"name":"Life and Health Sciences Research Institute (ICVS) School of Medicine University of Minho  Braga Portugal"},{"name":"ICVS\/3B's\u2010PT Government Associate Laboratory  Braga\/Guimar\u00e3es Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan M.","family":"Irache","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences School of Pharmacy and Nutrition University of Navarra  Pamplona 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