{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T18:23:31Z","timestamp":1781115811992,"version":"3.54.1"},"reference-count":65,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2024,1,15]],"date-time":"2024-01-15T00:00:00Z","timestamp":1705276800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Rho-kinase (ROCK) inhibitors represent a new category of anti-glaucoma medications. Among them, Fasudil hydrochloride, a selective ROCK inhibitor, has demonstrated promising outcomes in glaucoma treatment. It works by inhibiting the ROCK pathway, which plays a crucial role in regulating the trabecular meshwork and canal of Schlemm\u2019s aqueous humor outflow. This study aims to investigate the ocular absorption pathway of Fasudil hydrochloride and, subsequently, develop a nanoparticle-based delivery system for enhanced corneal absorption. Employing the ionic gelation method and statistical experimental design, the factors influencing chitosan nanoparticle (Cs NP) characteristics and performance were explored. Fasudil in vitro release and ex vivo permeation studies were performed, and Cs NP ocular tolerability and cytotoxicity on human lens epithelial cells were evaluated. Permeation studies on excised bovine eyes revealed significantly higher Fasudil permeation through the sclera compared to the cornea (370.0 \u03bcg\/cm2 vs. 96.8 \u03bcg\/cm2, respectively). The nanoparticle size (144.0 \u00b1 15.6 nm to 835.9 \u00b1 23.4 nm) and entrapment efficiency range achieved (17.2% to 41.4%) were predominantly influenced by chitosan quantity. Cs NPs showed a substantial improvement in the permeation of Fasudil via the cornea, along with slower release compared to the Fasudil aqueous solution. The results from the Hen\u2019s Egg Test Chorioallantoic Membrane (HET-CAM) and Bovine Corneal Opacity and Permeability (BCOP) tests indicated good conjunctival and corneal biocompatibility of the formulated chitosan nanoparticles, respectively. Lens epithelial cells displayed excellent tolerance to low concentrations of these nanoparticles (&gt;94% cell viability). To the best of our knowledge, this is the first report on the ocular absorption pathway of topically applied Fasudil hydrochloride where the cornea has been identified as a potential barrier that could be overcome using Cs NPs.<\/jats:p>","DOI":"10.3390\/pharmaceutics16010112","type":"journal-article","created":{"date-parts":[[2024,1,15]],"date-time":"2024-01-15T07:25:07Z","timestamp":1705303507000},"page":"112","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Exploring the Ocular Absorption Pathway of Fasudil Hydrochloride towards Developing a Nanoparticulate Formulation with Improved Performance"],"prefix":"10.3390","volume":"16","author":[{"given":"Barzan","family":"Osi","sequence":"first","affiliation":[{"name":"Drug Discovery, Delivery and Patient Care (DDDPC) Theme, School of Life Sciences, Pharmacy and Chemistry, Kingston University London, London KT1 2EE, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4940-7648","authenticated-orcid":false,"given":"Ali A.","family":"Al-Kinani","sequence":"additional","affiliation":[{"name":"Drug Discovery, Delivery and Patient Care (DDDPC) Theme, School of Life Sciences, Pharmacy and Chemistry, Kingston University London, London KT1 2EE, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zinah K.","family":"Al-Qaysi","sequence":"additional","affiliation":[{"name":"Drug Discovery, Delivery and Patient Care (DDDPC) Theme, School of Life Sciences, Pharmacy and Chemistry, Kingston University London, London KT1 2EE, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7640-471X","authenticated-orcid":false,"given":"Mouhamad","family":"Khoder","sequence":"additional","affiliation":[{"name":"Drug Discovery, Delivery and Patient Care (DDDPC) Theme, School of Life Sciences, Pharmacy and Chemistry, Kingston University London, London KT1 2EE, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0355-7499","authenticated-orcid":false,"given":"Raid G.","family":"Alany","sequence":"additional","affiliation":[{"name":"Drug Discovery, Delivery and Patient Care (DDDPC) Theme, School of Life Sciences, Pharmacy and Chemistry, Kingston University London, London KT1 2EE, UK"},{"name":"School of Pharmacy, The University of Auckland, Auckland 1010, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,1,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1016\/j.jcjo.2016.07.013","article-title":"Glaucoma Treatment Trends: A Review","volume":"52","author":"Conlon","year":"2017","journal-title":"Can. 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