{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T22:26:15Z","timestamp":1791411975829,"version":"4.3.3"},"reference-count":67,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2022,8,21]],"date-time":"2022-08-21T00:00:00Z","timestamp":1661040000000},"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>The objective and novelty of the present study is the development and optimization of innovative nasal film of Donepezil hydrochloride (DH) for potential use in Alzheimer\u2019s disease. Hydroxypropyl-methyl-cellulose E50 (factor A) nasal films, with Polyethylene glycol 400 as plasticizer (factor B), and Methyl-\u03b2-Cyclodextrin, as permeation enhancer (factor C), were prepared and characterized in vitro and ex vivo. An experimental design was used to determine the effects of the selected factors on permeation profile of DH through rabbit nasal mucosa (response 1), and on film flexibility\/foldability (response 2). A face centered central composite design with three levels was applied and 17 experiments were performed in triplicate. The prepared films exhibited good uniformity of DH content (90.0 \u00b1 1.6%\u201399.8 \u00b1 4.9%) and thickness (19.6 \u00b1 1.9\u2013170.8 \u00b1 11.5 \u03bcm), storage stability characteristics, and % residual humidity (&lt;3%), as well as favourable swelling and mucoadhesive properties. Response surface methodology determined the optimum composition for flexible nasal film with maximized DH permeation. All selected factors interacted with each other and the effect of these interactions on responses is strongly related to the factor\u2019s concentration ratios. Based on these encouraging results, in vivo serum and brain pharmacokinetic study of the optimized nasal film, in comparison to DH oral administration, is ongoing in an animal model.<\/jats:p>","DOI":"10.3390\/pharmaceutics14081742","type":"journal-article","created":{"date-parts":[[2022,8,22]],"date-time":"2022-08-22T01:56:40Z","timestamp":1661133400000},"page":"1742","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Development and In Vitro-Ex Vivo Evaluation of Novel Polymeric Nasal Donepezil Films for Potential Use in Alzheimer\u2019s Disease Using Experimental Design"],"prefix":"10.3390","volume":"14","author":[{"given":"Paraskevi","family":"Papakyriakopoulou","sequence":"first","affiliation":[{"name":"Department of Pharmacy, School of Health Sciences, National and Kapodistrian University of Athens, 15784 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimitrios M.","family":"Rekkas","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, School of Health Sciences, National and Kapodistrian University of Athens, 15784 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9033-2305","authenticated-orcid":false,"given":"Gaia","family":"Colombo","sequence":"additional","affiliation":[{"name":"Department of Life Sciences and Biotechnology, University of Ferrara, 44121 Ferrara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2395-6844","authenticated-orcid":false,"given":"Georgia","family":"Valsami","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, School of Health Sciences, National and Kapodistrian University of Athens, 15784 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,21]]},"reference":[{"key":"ref_1","first-page":"11","article-title":"Pathways for small molecule delivery to the central nervous system across the blood-brain barrier","volume":"6","author":"Mikitsh","year":"2014","journal-title":"Perspect. 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