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Standard treatment is with oral metronidazole or tinidazole, but resistance is emerging and adverse effects can be problematic. Topical treatment offers potential benefits for increasing local drug concentrations while reducing systemic exposure, but none are currently approved for trichomoniasis. The anti\u2010rheumatic drug, auranofin (AF), was recently discovered to have significant trichomonacidal activity, but has a long plasma half\u2010life and significant adverse effects. Here, this drug is used as a model to develop a novel topical formulation composed of AF\u2010loaded nanoparticles (NP) embedded in a thermoresponsive hydrogel for intravaginal administration. The AF\u2010NP composite gel shows sustained drug release for at least 12 h, and underwent sol\u2013gel transition with increased viscoelasticity within a minute. Intravaginal administration in mice shows excellent NP retention for &gt;6 h and markedly increases local AF levels, but reduces plasma and liver levels compared to oral treatment with a much higher dose. Furthermore, intravaginal AF\u2010NP gel greatly outperforms oral AF in eliminating vaginal trichomonad infection in mice, while causing no systemic or local toxicity. These results show the potential of the AF\u2010NP hydrogel formulation for effective topical therapy of vaginal infections.<\/jats:p>","DOI":"10.1002\/adtp.201900157","type":"journal-article","created":{"date-parts":[[2019,10,30]],"date-time":"2019-10-30T06:40:03Z","timestamp":1572417603000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Composite Thermoresponsive Hydrogel with Auranofin\u2010Loaded Nanoparticles for Topical Treatment of Vaginal Trichomonad Infection"],"prefix":"10.1002","volume":"2","author":[{"given":"Yue","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of NanoEngineering and Moores Cancer Center University of California San Diego  La Jolla CA 92093 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukiko","family":"Miyamoto","sequence":"additional","affiliation":[{"name":"Department of Medicine University of California San Diego  La Jolla CA 92093 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sozaburo","family":"Ihara","sequence":"additional","affiliation":[{"name":"Department of Medicine University of California San Diego  La Jolla CA 92093 USA"},{"name":"Division of Gastroenterology The Institute for Adult Diseases Asahi Life Foundation  Tokyo 103\u20100002 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin Z.","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Medicine University of California San Diego  La Jolla CA 92093 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas E.","family":"Zuill","sequence":"additional","affiliation":[{"name":"Department of Medicine University of California San Diego  La Jolla CA 92093 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pavimol","family":"Angsantikul","sequence":"additional","affiliation":[{"name":"Department of NanoEngineering and Moores Cancer Center University of California San Diego  La Jolla CA 92093 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiangzhe","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of NanoEngineering and Moores Cancer Center University of California San Diego  La Jolla CA 92093 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiwei","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of NanoEngineering and Moores Cancer Center University of California San Diego  La Jolla CA 92093 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0637-0654","authenticated-orcid":false,"given":"Liangfang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of NanoEngineering and Moores Cancer Center University of California San Diego  La Jolla CA 92093 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"Eckmann","sequence":"additional","affiliation":[{"name":"Department of Medicine University of California San Diego  La Jolla CA 92093 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,10,30]]},"reference":[{"key":"e_1_2_8_1_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciy079"},{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.3109\/1040841X.2015.1105782"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10552-017-0919-6"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejogrb.2018.06.031"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11908-015-0484-7"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1258\/0956462053654258"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1071\/SH09011"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.3201\/eid1806.111590"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1086\/323034"},{"key":"e_1_2_8_10_1","first-page":"60","volume":"26","author":"Andersson K. 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