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The \u03b2CD-derived nanosponges provide host\u2013guest cavities for drug inclusion, while the PVA network acts as a diffusion-regulating matrix. Initially, adsorption\u2013desorption studies were performed on isolated CDNSs to evaluate their drug-loading capacity prior to incorporation into the hydrogels. The CDNSs exhibited efficient encapsulation (\u223c60%) and released more than 90% of the drug, confirming strong yet reversible host\u2013guest interactions within CDs cavities. The drug-loaded CDNSs were subsequently dispersed in PVA solutions and physically cross-linked by freeze\u2013thaw cycling, producing hydrogels containing embedded supramolecular reservoirs. Increasing the PVA concentration (from 14 to 20% w\/v) generated denser polymer networks, reducing the swelling degree from \u223c60 to \u223c30 and slowing water uptake. CDNSs incorporation altered the hydrogel microstructure and introduced additional drug\u2013matrix interactions, resulting in reduced burst release, measurable lag times, and more prolonged release compared with neat PVA hydrogels. Release kinetics were best described by the Weibull model, indicating diffusion-controlled transport in the pure matrices and heterogeneous diffusion behavior in the hybrid systems. Overall, AMT release is governed by coupled mechanisms involving diffusion through the polymer network and dissociation from cyclodextrin host sites, with CDNSs acting as supramolecular reservoirs within the hydrogel matrix.<\/jats:p>","DOI":"10.1021\/acsomega.6c03745","type":"journal-article","created":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T16:38:50Z","timestamp":1784219930000},"page":"43942-43953","source":"Crossref","is-referenced-by-count":1,"title":["Cyclodextrin Nanosponge\u2013PVA\nHybrid Networks\nas Supramolecular Reservoir Systems for Amitriptyline"],"prefix":"10.1021","volume":"11","author":[{"given":"Bianca B. M.","family":"Vieira","sequence":"first","affiliation":[{"name":"Universidade Federal de Itajuba\u0301 (UNIFEI) , , , ,","place":["Itajuba\u0301, MG, Brazil, 37500-903"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2121-7797","authenticated-orcid":true,"given":"Pedro M. 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