{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T16:02:06Z","timestamp":1789142526104,"version":"build-2803163510"},"reference-count":57,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2024,11,21]],"date-time":"2024-11-21T00:00:00Z","timestamp":1732147200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002383","name":"King Saud University","doi-asserted-by":"publisher","award":["RSPD2024R668"],"award-info":[{"award-number":["RSPD2024R668"]}],"id":[{"id":"10.13039\/501100002383","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background\/Objectives: Nitazoxanide (NTX) exhibits promising therapeutic potential; its effectiveness is constrained by its low oral bioavailability due to its poor water solubility and limited permeability. Methods: This study focused on developing a complex of NTX with \u03b2-cyclodextrins (\u03b2-CDs), specifically \u03b2-CD and hydroxypropyl-\u03b2-cyclodextrin (H\u03b2-CD), to enhance the solubility and antiviral activity of NTX. Results: The formation of the \u03b2-CD:NTX in an aqueous solution was verified using UV\u2013visible spectroscopy, confirming a 1:1 inclusion complex. Characterization of the solid \u03b2-CD:NTX complexes was confirmed via FTIR, X-ray diffraction (XRD), scanning electron microscopy (SEM), and DSC-TGA analyses. Molecular docking studies revealed that the NTX thiazole ring with the nitro group was positioned within the \u03b2-CDs cavity, while the benzene ring remained outside. Phase solubility tests showed that \u03b2-CD:NTX complexes were formed with high stability constants, demonstrating a linear increase in NTX solubility as the \u03b2-CD concentration increased. Dissolution tests revealed rapid and nearly complete NTX release within 90 min for \u03b2-CD:NTX and H\u03b2-CD:NTX complexes. The \u03b2-CD:NTX complexes were tested for their antiviral activity against Herpes simplex virus (HSV-1) cultures. Results showed that the H\u03b2-CD:NTX complex had significantly higher antiviral efficacy than \u03b2-CD:NTX and free NTX alone. Moreover, cytotoxicity and cellular uptake studies on Vero cells indicated that the H\u03b2-CD:NTX complex demonstrated lower cytotoxicity and had the highest IC50 value, followed by \u03b2-CD:NTX and free NTX. Conclusions: These findings suggest that H\u03b2-CD:NTX inclusion complexes may serve as effective carriers for delivering NTX in HSV-1 treatments using Vero cell models.<\/jats:p>","DOI":"10.3390\/pharmaceutics16121494","type":"journal-article","created":{"date-parts":[[2024,11,21]],"date-time":"2024-11-21T12:25:42Z","timestamp":1732191942000},"page":"1494","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Formulation and Characterization of \u03b2-Cyclodextrins\u2013Nitazoxanide Inclusion Complexes: Enhanced Solubility, In Vitro Drug Release, and Antiviral Activity in Vero Cells"],"prefix":"10.3390","volume":"16","author":[{"given":"Kuppu","family":"Sakthi Velu","sequence":"first","affiliation":[{"name":"School of Chemical Engineering, Yeungnam University, Gyeongsan 38541, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonamuthu","family":"Jegatheeswaran","sequence":"additional","affiliation":[{"name":"BioMe Live Analytical Centre, Karaikudi 630003, Tamil Nadu, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5486-4408","authenticated-orcid":false,"given":"Muhammad Saeed","family":"Akhtar","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Yeungnam University, Gyeongsan 38541, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6270-8539","authenticated-orcid":false,"given":"Mohammad Rizwan","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Chemistry, College of Science, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4749-2247","authenticated-orcid":false,"given":"Sonaimuthu","family":"Mohandoss","sequence":"additional","affiliation":[{"name":"School of Chemical Engineering, Yeungnam University, Gyeongsan 38541, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2913-1763","authenticated-orcid":false,"given":"Naushad","family":"Ahmad","sequence":"additional","affiliation":[{"name":"Department of Chemistry, College of Science, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1111\/odi.14635","article-title":"Management of Oral Herpes Simplex Virus Infections: The Problem of Resistance. 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