{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T13:03:16Z","timestamp":1791378196444,"version":"4.3.2"},"reference-count":72,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,10,21]],"date-time":"2021-10-21T00:00:00Z","timestamp":1634774400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2014\/14457-5"],"award-info":[{"award-number":["2014\/14457-5"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2018\/25920-9"],"award-info":[{"award-number":["2018\/25920-9"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2019\/07245-5"],"award-info":[{"award-number":["2019\/07245-5"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004916","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado do Amazonas","doi-asserted-by":"publisher","award":["-"],"award-info":[{"award-number":["-"]}],"id":[{"id":"10.13039\/501100004916","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["-"],"award-info":[{"award-number":["-"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Recent advances have been reported for needle-free local anesthesia in maxillary teeth by administering a nasal spray of tetracaine (TTC) and oxymetazoline, without causing pain, fear, and stress. This work aimed to assess whether a TTC-loaded hybrid system could reduce cytotoxicity, promote sustained permeation, and increase the anesthetic efficacy of TTC for safe, effective, painless, and prolonged analgesia of the maxillary teeth in dental procedures. The hybrid system based on TTC (4%) encapsulated in nanostructured lipid carriers (NLC) and incorporated into a thermoreversible hydrogel of poloxamer 407 (TTCNLC-HG4%) displayed desirable rheological, mechanical, and mucoadhesive properties for topical application in the nasal cavity. Compared to control formulations, the use of TTCNLC-HG4% slowed in vitro permeation of the anesthetic across the nasal mucosa, maintained cytotoxicity against neuroblastoma cells, and provided a three-fold increase in analgesia duration, as observed using the tail-flick test in mice. The results obtained here open up perspectives for future clinical evaluation of the thermoreversible hybrid hydrogel, which contains TTC-loaded NLC, with the aim of creating an effective, topical, intranasal, needle-free anesthesia for use in dentistry.<\/jats:p>","DOI":"10.3390\/pharmaceutics13111760","type":"journal-article","created":{"date-parts":[[2021,10,21]],"date-time":"2021-10-21T23:27:39Z","timestamp":1634858859000},"page":"1760","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Mucoadhesive, Thermoreversible Hydrogel, Containing Tetracaine-Loaded Nanostructured Lipid Carriers for Topical, Intranasal Needle-Free Anesthesia"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1041-5835","authenticated-orcid":false,"given":"Giovana Maria Fioramonti","family":"Calixto","sequence":"first","affiliation":[{"name":"Department of Biosciences, Piracicaba Dental School, University of Campinas-UNICAMP, Piracicaba 13414-903, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno Vilela","family":"Muniz","sequence":"additional","affiliation":[{"name":"Department of Biosciences, Piracicaba Dental School, University of Campinas-UNICAMP, Piracicaba 13414-903, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9427-5328","authenticated-orcid":false,"given":"Simone R.","family":"Castro","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas-UNICAMP, Campinas 13083-872, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaiza Samara Macena","family":"de Araujo","sequence":"additional","affiliation":[{"name":"Department of Biosciences, Piracicaba Dental School, University of Campinas-UNICAMP, Piracicaba 13414-903, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4693-1356","authenticated-orcid":false,"given":"Klinger","family":"de Souza Amorim","sequence":"additional","affiliation":[{"name":"Department of Biosciences, Piracicaba Dental School, University of Campinas-UNICAMP, Piracicaba 13414-903, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6097-5449","authenticated-orcid":false,"given":"L\u00edgia N. M.","family":"Ribeiro","sequence":"additional","affiliation":[{"name":"Institute of Biotechnology, Federal University of Uberlandia-UFU, Uberlandia 38405-302, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4882-5402","authenticated-orcid":false,"given":"Luiz Eduardo Nunes","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Laboratory of Inflammation and Immunology, Guarulhos University-UNG, Guarulhos 07023-070, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9289-4229","authenticated-orcid":false,"given":"Daniele Ribeiro","family":"de Ara\u00fajo","sequence":"additional","affiliation":[{"name":"Human and Natural Sciences Center, Federal University of ABC-UFABC, Santo Andr\u00e9 09210-580, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4504-5723","authenticated-orcid":false,"given":"Eneida","family":"de Paula","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas-UNICAMP, Campinas 13083-872, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0760-1389","authenticated-orcid":false,"given":"Michelle","family":"Franz-Montan","sequence":"additional","affiliation":[{"name":"Department of Biosciences, Piracicaba Dental School, University of Campinas-UNICAMP, Piracicaba 13414-903, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/j.joen.2018.12.003","article-title":"Anesthetic Efficacy of Intranasal 3% Tetracaine plus 0.05% Oxymetazoline (Kovanaze) in Maxillary Teeth","volume":"45","author":"Capetillo","year":"2019","journal-title":"J. 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