{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T03:09:46Z","timestamp":1791947386356,"version":"4.3.4"},"reference-count":50,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2025,2,4]],"date-time":"2025-02-04T00:00:00Z","timestamp":1738627200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background: The neuroprotective efficacy of glibenclamide (GLIB) has been demonstrated in multiple rodent models of ischemia, hemorrhagic stroke, traumatic brain damage, spinal cord injury, and metastatic brain tumors. Due to its poor solubility, GLIB has low oral bioavailability, limiting its transportation to the brain via the oral route. Objectives: Here, we attempted to develop and optimize an intranasal mucoadhesive in situ gel of GLIB-loaded bilosomes using a 32 Box\u2013Behnken design for brain drug delivery. Methods: To facilitate a longer residence time of the administered dose within the nasal cavity, the prepared bilosomes were loaded into a mucoadhesive in situ gel providing resistance to rapid mucociliary clearance. The amounts of sodium deoxycholate, the cholesterol\/Span 40 mixture, and the molar ratio between the mixture\u2019s components were chosen as independent variables, while the entrapment efficiency and in vitro drug release were selected as dependent variables. Results and conclusions: The optimal formulation was analyzed for particle size and entrapment efficiency, which were found to be 270.6 nm and 68.39%, respectively. In vitro drug release from optimal formulation after 12 h was 87.29 \u00b1 1.98% as compared to 52.01 \u00b1 2.04% of plain in situ gel of drug. An in vivo brain drug delivery study performed on Swiss albino mice showed that the brain concentration of drug through intranasal administration from mucoadhesive in situ gel of GLIB-bilosomes after 12 h was 2.12 \u00b1 0.16 \u00b5g\/mL as compared to 0.68 \u00b1 0.04 \u00b5g\/mL from plain in situ gel of drug. Conclusively, the developed bilosomal formulation offers a favorable intranasal substitute with enhanced therapeutic drug delivery to the brain.<\/jats:p>","DOI":"10.3390\/pharmaceutics17020193","type":"journal-article","created":{"date-parts":[[2025,2,4]],"date-time":"2025-02-04T05:55:22Z","timestamp":1738648522000},"page":"193","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Intranasal Mucoadhesive In Situ Gel of Glibenclamide-Loaded Bilosomes for Enhanced Therapeutic Drug Delivery to the Brain"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-5574-0560","authenticated-orcid":false,"given":"Meenakshi","family":"Tripathi","sequence":"first","affiliation":[{"name":"School of Pharmaceutical Sciences, Shoolini University of Biotechnology and Management Sciences, Solan 173229, Himachal Pradesh, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-3561-0783","authenticated-orcid":false,"given":"Laxmi","family":"Gharti","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Shoolini University of Biotechnology and Management Sciences, Solan 173229, Himachal Pradesh, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amit","family":"Bansal","sequence":"additional","affiliation":[{"name":"Formulation Research and Development, Perrigo Company plc, Allegan, MI 49010, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6810-1276","authenticated-orcid":false,"given":"Hemlata","family":"Kaurav","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Shoolini University of Biotechnology and Management Sciences, Solan 173229, Himachal Pradesh, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6570-8120","authenticated-orcid":false,"given":"Sandeep","family":"Sheth","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Pharmacy, Larkin University, Miami, FL 33169, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"122759","DOI":"10.1016\/j.ijpharm.2023.122759","article-title":"Access to the CNS: Strategies to overcome the BBB","volume":"636","author":"Bermejo","year":"2023","journal-title":"Int. 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