{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T13:10:12Z","timestamp":1793193012036,"version":"4.5.0"},"reference-count":100,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2024,5,28]],"date-time":"2024-05-28T00:00:00Z","timestamp":1716854400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Cyclodextrins (CDs) are cyclic oligosaccharides able to form noncovalent water-soluble complexes useful in many different applications for the solubilization, delivery, and greater bioavailability of hydrophobic drugs. The complexation of 5-fluorouracil (5-FU) with natural or synthetic cyclodextrins permits the solubilization of this poorly soluble anticancer drug. In this theoretical work, the complexes between \u03b2-CD and 5-FU are investigated using molecular mechanics (MM) and molecular dynamics (MD) simulations in water. The inclusion complexes are formed thanks to the favorable intermolecular interactions between \u03b2-CD and 5-FU. Both 1:1 and 1:2 \u03b2-CD\/5-FU stoichiometries are investigated, providing insight into their interaction geometries and stability over time in water. In the 1:2 \u03b2-CD\/5-FU complexes, the intermolecular interactions affect the drug\u2019s mobility, suggesting a two-step release mechanism: a fast release for the more exposed and hydrated drug molecule, with greater freedom of movement near the \u03b2-CD rims, and a slow one for the less-hydrated and well-encapsulated and confined drug. MD simulations study the intermolecular interactions between drugs and specific carriers at the atomistic level, suggesting a possible release mechanism and highlighting the role of the impact of the drug concentration on the kinetics process in water. A comparison with experimental data in the literature provides further insights.<\/jats:p>","DOI":"10.3390\/ijms25115888","type":"journal-article","created":{"date-parts":[[2024,5,28]],"date-time":"2024-05-28T13:32:55Z","timestamp":1716903175000},"page":"5888","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Different Drug Mobilities in Hydrophobic Cavities of Host\u2013Guest Complexes between \u03b2-Cyclodextrin and 5-Fluorouracil at Different Stoichiometries: A Molecular Dynamics Study in Water"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3462-6514","authenticated-orcid":false,"given":"Giuseppina","family":"Raffaini","sequence":"first","affiliation":[{"name":"Department of Chemistry, Materials, and Chemical Engineering \u201cGiulio Natta\u201d, Politecnico di Milano, Piazza L. Da Vinci 32, 20131 Milano, Italy"},{"name":"INSTM, National Consortium of Materials Science and Technology, Local Unit Politecnico di Milano, 50121 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0686-2480","authenticated-orcid":false,"given":"Stefano","family":"Elli","sequence":"additional","affiliation":[{"name":"Istituto di Ricerche Chimiche e Biochimiche \u2018G. Ronzoni\u2019, Via Giuseppe Colombo 81, 20133 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4448-6984","authenticated-orcid":false,"given":"Michelina","family":"Catauro","sequence":"additional","affiliation":[{"name":"Department of Engineering, University of Campania \u201cLuigi Vanvitelli\u201d, Via Roma 29, 81031 Aversa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7768-8745","authenticated-orcid":false,"given":"Antonio","family":"D\u2019Angelo","sequence":"additional","affiliation":[{"name":"Department of Engineering, University of Campania \u201cLuigi Vanvitelli\u201d, Via Roma 29, 81031 Aversa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"10940","DOI":"10.1021\/cr500081p","article-title":"Review: A history of Cyclodextrins","volume":"114","author":"Crini","year":"2014","journal-title":"Chem. 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