{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T01:43:58Z","timestamp":1792806238565,"version":"4.5.0"},"reference-count":49,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,1,27]],"date-time":"2023-01-27T00:00:00Z","timestamp":1674777600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Deanship of scientific research at King Saud University","id":[{"id":"https:\/\/ror.org\/02f81g417","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>This study investigates the development of topically applied non-invasive amino-functionalized silica nanoparticles (AMSN) and O-Carboxymethyl chitosan-coated AMSN (AMSN-CMC) for ocular delivery of 5-Fluorouracil (5-FU). Particle characterization was performed by the DLS technique (Zeta-Sizer), and structural morphology was examined by SEM and TEM. The drug encapsulation and loading were determined by the indirect method using HPLC. Physicochemical characterizations were performed by NMR, TGA, FTIR, and PXRD. In vitro release was conducted through a dialysis membrane in PBS (pH 7.4) using modified Vertical Franz diffusion cells. The mucoadhesion ability of the prepared nanoparticles was tested using the particle method by evaluating the change in zeta potential. The transcorneal permeabilities of 5-FU from AMNS-FU and AMSN-CMC-FU gel formulations were estimated through excised goat cornea and compared to that of 5-FU gel formulation. Eye irritation and ocular pharmacokinetic studies from gel formulations were evaluated in rabbit eyes. The optimum formulation of AMSN-CMC-FU was found to be nanoparticles with a particle size of 249.4 nm with a polydispersity of 0.429, encapsulation efficiency of 25.8 \u00b1 5.8%, and drug loading capacity of 5.2 \u00b1 1.2%. NMR spectra confirmed the coating of AMSN with the CMC layer. In addition, TGA, FTIR, and PXRD confirmed the drug loading inside the AMSN-CMC. Release profiles showed 100% of the drug was released from the 5-FU gel within 4 h, while AMSN-FU gel released 20.8% of the drug and AMSN-CMC-FU gel released around 55.6% after 4 h. AMSN-CMC-FU initially exhibited a 2.45-fold increase in transcorneal flux and apparent permeation of 5-FU compared to 5-FU gel, indicating a better corneal permeation. Higher bioavailability of AMSN-FU and AMSN-CMC-FU gel formulations was found compared to 5-FU gel in the ocular pharmacokinetic study with superior pharmacokinetics parameters of AMSN-CMC-FU gel. AMSN-CMC-FU showed 1.52- and 6.14-fold higher AUC0-inf in comparison to AMSN-FU and 5-FU gel, respectively. AMSN-CMC-FU gel and AMSN-FU gel were \u201cminimally irritating\u201d to rabbit eyes but showed minimal eye irritation potency in comparison to the 5 FU gel. Thus, the 5-FU loaded in AMSN-CMC gel could be used as a topical formulation for the treatment of ocular cancer.<\/jats:p>","DOI":"10.3390\/molecules28031260","type":"journal-article","created":{"date-parts":[[2023,1,30]],"date-time":"2023-01-30T02:01:18Z","timestamp":1675044078000},"page":"1260","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Mesoporous Silica Nanoparticles Coated with Carboxymethyl Chitosan for 5-Fluorouracil Ocular Delivery: Characterization, In Vitro and In Vivo Studies"],"prefix":"10.3390","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6244-9407","authenticated-orcid":false,"given":"Adel Ali","family":"Alhowyan","sequence":"first","affiliation":[{"name":"Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5713-8858","authenticated-orcid":false,"given":"Mohd Abul","family":"Kalam","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia"},{"name":"Nanobiotechnology Unit, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5821-5600","authenticated-orcid":false,"given":"Muzaffar","family":"Iqbal","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11495, Saudi Arabia"},{"name":"Central Lab, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6015-6125","authenticated-orcid":false,"given":"Mohammad","family":"Raish","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed M.","family":"El-Toni","sequence":"additional","affiliation":[{"name":"King Abdullah Institute for Nanotechnology, King Saud University, Riyadh 11495, Saudi Arabia"},{"name":"Nanomaterials and Nanotechnology Department, Central Metallurgical Research and Development Institute (CMRDI), Helwan, Cairo 11865, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Musaed","family":"Alkholief","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia"},{"name":"Nanobiotechnology Unit, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0181-6330","authenticated-orcid":false,"given":"Aliyah A.","family":"Almomen","sequence":"additional","affiliation":[{"name":"Nanobiotechnology Unit, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia"},{"name":"Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11495, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8950-6571","authenticated-orcid":false,"given":"Aws","family":"Alshamsan","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia"},{"name":"Nanobiotechnology Unit, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,27]]},"reference":[{"key":"ref_1","first-page":"801","article-title":"5-Fluorouracil for the treatment of intraepithelial neoplasia and squamous cell carcinoma of the conjunctiva, and cornea","volume":"4","year":"2010","journal-title":"Clin. 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