{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T19:32:29Z","timestamp":1792524749998,"version":"4.5.0"},"reference-count":83,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T00:00:00Z","timestamp":1778889600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background: Baicalein (BA) is a poorly soluble flavonoid with limited oral bioavailability. This study aimed to enhance the solubility and nasal absorption of the compound using a dual-carrier system that combines cyclodextrin inclusion complexes and thermosensitive hydrogels. Methods: The inclusion complexes of BA with hydroxypropyl-\u03b2-cyclodextrin (HP-\u03b2-CD) or sulfobutyl-\u03b2-cyclodextrin (SBE-\u03b2-CD), namely BA-HP-\u03b2-CD and BA-SBE-\u03b2-CD, were prepared via solution stirring and characterized by solubility, dissolution, scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), thermogravimetric analysis-differential scanning calorimetry (TG-DSC), and Madin-Darby canine kidney (MDCK) cell permeation. The optimal complexes were incorporated into chitosan\/\u03b2-glycerophosphate thermosensitive hydrogels (BA\/HP-Gel and BA\/SBE-Gel), followed by evaluations of gelation properties, in vitro release, and in vivo pharmacokinetics in rats. Results: The water solubility of BA-HP-\u03b2-CD and BA-SBE-\u03b2-CD increased 572 and 582 times, with MDCK permeability enhanced by 5.3 and 2.9 times, respectively. Both hydrogels showed rapid solution-gel transition at nasal temperature and sustained release. Following intranasal administration, BA\/HP-Gel and BA\/SBE-Gel achieved relative bioavailabilities of 623.5% and 697.8%, respectively, compared with BA-Gel. Conclusions: The dual-carrier platform effectively improved BA solubility, permeability, and nasal bioavailability, offering a promising strategy for nasal delivery of poorly soluble drugs.<\/jats:p>","DOI":"10.3390\/ph19050781","type":"journal-article","created":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T13:12:08Z","timestamp":1779455528000},"page":"781","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Baicalein-Cyclodextrin Inclusion Complexes Nasal Thermosensitive Hydrogel: Bioavailability Improvement and Pharmacokinetic Evaluation in Rats"],"prefix":"10.3390","volume":"19","author":[{"given":"Xinyu","family":"Ji","sequence":"first","affiliation":[{"name":"School of Pharmacy, Hangzhou Medical College, Hangzhou 311399, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiali","family":"Wei","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Hangzhou Medical College, Hangzhou 311399, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zixuan","family":"Guo","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Hangzhou Medical College, Hangzhou 311399, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziyang","family":"Li","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Hangzhou Medical College, Hangzhou 311399, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxian","family":"Li","sequence":"additional","affiliation":[{"name":"Traditional Chinese Medicine Department, Jilin Agricultural Science and Technology College, Jilin 132102, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-3046-5688","authenticated-orcid":false,"given":"Rui","family":"Yang","sequence":"additional","affiliation":[{"name":"NMPA Key Laboratory for Quality Research and Evaluation of Pharmaceutical Excipients, National Institutes for Food and Drug Control, Beijing 100050, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingri","family":"Jin","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Hangzhou Medical College, Hangzhou 311399, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"118183","DOI":"10.1016\/j.lfs.2020.118183","article-title":"Baicalein: A metabolite with promising antineoplastic activity","volume":"259","author":"Tuli","year":"2020","journal-title":"Life Sci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1007\/s00705-018-4083-4","article-title":"Baicalein and baicalin as Zika virus inhibitors","volume":"164","author":"Oo","year":"2019","journal-title":"Arch. 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