{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T22:02:25Z","timestamp":1789596145080,"version":"build-2803163510"},"reference-count":77,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2023,8,7]],"date-time":"2023-08-07T00:00:00Z","timestamp":1691366400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007614","name":"Deanship of Scientific Research at Jouf University","doi-asserted-by":"publisher","award":["DSR2022-RG-0143"],"award-info":[{"award-number":["DSR2022-RG-0143"]}],"id":[{"id":"10.13039\/501100007614","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Depression is a serious mental disorder and the most prevalent cause of disability and suicide worldwide. Quercetin (QER) demonstrated antidepressant effects in rats exhibiting anxiety and depressive-like behaviors. In an attempt to improve QER\u2019s antidepressant activity, a QER-loaded transferosome (QER-TFS) thermosensitive gel for intranasal administration was formulated and optimized. The therapeutic effectiveness of the optimized formulation was assessed in a depressed rat model by conducting a behavioral analysis. Behavioral study criteria such as immobility, swimming, climbing, sucrose intake, number of crossed lines, rearing, active interaction, and latency to feed were all considerably enhanced by intranasal treatment with the QER-TFS in situ gel in contrast to other formulations. A nasal histopathological study indicated that the QER-TFS thermosensitive gel was safe for the nasal mucosa. An immunohistochemical analysis showed that the animals treated with the QER-TFS thermosensitive gel had the lowest levels of c-fos protein expression, and brain histopathological changes in the depressed rats were alleviated. According to pharmacodynamic, immunohistochemical, and histopathological experiments, the intranasal administration of the QER-TFS thermosensitive gel substantially alleviated depressive symptoms in rats. However, extensive preclinical investigations in higher animal models are needed to anticipate its effectiveness in humans.<\/jats:p>","DOI":"10.3390\/pharmaceutics15082095","type":"journal-article","created":{"date-parts":[[2023,8,8]],"date-time":"2023-08-08T12:35:42Z","timestamp":1691498142000},"page":"2095","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Intranasal Nanotransferosomal Gel for Quercetin Brain Targeting: II. Antidepressant Effect in an Experimental Animal Model"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4083-6024","authenticated-orcid":false,"given":"Mohammed H.","family":"Elkomy","sequence":"first","affiliation":[{"name":"Department of Pharmaceutics, College of Pharmacy, Jouf University, Sakaka 72341, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatma I.","family":"Abo El-Ela","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Veterinary Medicine, Beni-Suef University, Beni-Suef 62511, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Randa Mohammed","family":"Zaki","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia"},{"name":"Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62511, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2848-2932","authenticated-orcid":false,"given":"Omar A.","family":"Alsaidan","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, College of Pharmacy, Jouf University, Sakaka 72341, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2393-8195","authenticated-orcid":false,"given":"Mohammed","family":"Elmowafy","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, College of Pharmacy, Jouf University, Sakaka 72341, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0181-0278","authenticated-orcid":false,"given":"Ameeduzzafar","family":"Zafar","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, College of Pharmacy, Jouf University, Sakaka 72341, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khaled","family":"Shalaby","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, College of Pharmacy, Jouf University, Sakaka 72341, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9035-5638","authenticated-orcid":false,"given":"Mohamed A.","family":"Abdelgawad","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, College of Pharmacy, Jouf University, Sakaka 72341, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4670-8149","authenticated-orcid":false,"given":"Hany A.","family":"Omar","sequence":"additional","affiliation":[{"name":"College of Pharmacy, University of Sharjah, Sharjah 27272, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rania","family":"Salama","sequence":"additional","affiliation":[{"name":"Macquarie Medical School, Faculty of Medicine, Health and Human Sciences, Macquarie University, Macquarie Park, NSW 2109, Australia"},{"name":"Woolcock Institute of Medical Research, Glebe, NSW 2037, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5488-8602","authenticated-orcid":false,"given":"Hussein M.","family":"Eid","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62511, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Silvestro, S., Bramanti, P., and Mazzon, E. 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