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Cellular uptake on Caco-2 cells was 1.75 times higher for highly thiolated CDs than for unmodified CD. In vitro residence time on porcine intestine was prolonged 7-, 8.4-, and 7.9-fold for CD-SH, CD-SS-PEG 1\u00a0kDa, and CD-SS-PEG 2\u00a0kDa, respectively. In vivo results indicated CD-SS-PEG 1\u00a0kDa had the highest potential. Our comprehensive in vitro, ex vivo, and in vivo ffindings demonstrate that CD-SS-PEG 1\u00a0kDa is a highly promising candidate for mucoadhesive drug delivery systems.<\/jats:p>\n          <jats:p>\n            <jats:bold>Graphical Abstract<\/jats:bold>\n          <\/jats:p>","DOI":"10.1007\/s13346-025-01832-w","type":"journal-article","created":{"date-parts":[[2025,3,21]],"date-time":"2025-03-21T15:24:01Z","timestamp":1742570641000},"page":"3753-3767","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Cyclodextrin-mediated enhancement of gastrointestinal drug delivery: unveiling mucoadhesive and mucopenetrating synergy"],"prefix":"10.1007","volume":"15","author":[{"given":"Soheil","family":"Haddadzadegan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmad","family":"Saleh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florina","family":"Veider","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Knoll","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flavia","family":"Laffleur","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gergely","family":"Kali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4187-8277","authenticated-orcid":false,"given":"Andreas","family":"Bernkop-Schn\u00fcrch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,3,20]]},"reference":[{"key":"1832_CR1","doi-asserted-by":"crossref","unstructured":"Kali G, Haddadzadegan S, Bernkop-Schn\u00fcrch A. 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We affirm that the manuscript is original, free of conflicts, and complies with ethical and copyright requirements.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors adhered to the ARRIVE guidelines, conducting all experiments in accordance with the Regulations of the Experimental Animal Administration and the Principles of Laboratory Animal Care, with approval from the Animal Ethical Committee in Vienna, Austria (Reference code: 2021\u20130.721.001). The studies complied with the EU Directive 2010\/63 for animal protection. Sprague\u2013Dawley rats, housed in a controlled environment with stable temperature, humidity, and unlimited food and water, were chosen for their established relevance in biomedical research due to their similarity to human biological systems. All procedures were designed to minimize suffering, with humane euthanasia performed using CO\u2082 inhalation in accordance with AVMA Guidelines, ensuring both animal welfare and experimental integrity.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"No potential conflict of interest was reported by the author(s).","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}