{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T10:58:42Z","timestamp":1788001122678,"version":"build-2784847793"},"reference-count":35,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2022,1,26]],"date-time":"2022-01-26T00:00:00Z","timestamp":1643155200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Acta Ophthalmologica"],"published-print":{"date-parts":[[2022,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Purpose<\/jats:title><jats:p>Tyrosine kinase inhibitors inhibit VEGF receptors. If delivered to the retina, they might inhibit oedema and neovascularization such as in age\u2010related macular degeneration and diabetic retinopathy. The aim of this study was to formulate cediranib maleate, a potent VEGF inhibitor, as \u03b3\u2010cyclodextrin nanoparticle eye drops and measure the retinal delivery and overall ocular pharmacokinetics after a single\u2010dose administration in rabbits.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A novel formulation technology with 3% cediranib maleate as \u03b3\u2010cyclodextrin micro\u2010suspension was prepared by autoclaving method. Suitable stabilizers were tested for heat\u2010stable eye drops. The ophthalmic formulation was topically applied to one eye in rabbits. The pharmacokinetics in ocular tissues, tear film and blood samples were studied at 1, 3 and 6\u2009hr after administration.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>\u03b3\u2010cyclodextrin formed complex with cediranib maleate. The formation of \u03b3\u2010cyclodextrin nanoparticles occurred in concentrated complexing media. Combined stabilizers prevented the degradation of drug during the autoclaving process. Three hours after administration of the eye drops, treated eyes showed cediranib levels of 737\u2009\u00b1\u2009460\u2009nM (mean\u2009\u00b1\u2009SD) in the retina and 10\u2009\u00b1\u20096\u2009nM in the vitreous humour.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Cediranib maleate in \u03b3\u2010cyclodextrin nanoparticles were stable to heat in presence of stabilizers. The drug as eye drops reached the retina in concentrations that are more than 100 times higher than the 0.4\u2009nM IC<jats:sub>50<\/jats:sub> value reported for the VEGF type\u2010II receptor and thus, presumably, above therapeutic level. These results suggest that \u03b3\u2010cyclodextrin\u2010based cediranib maleate eye drops deliver effective drug concentrations to the retina in rabbits after a single\u2010dose administration.<\/jats:p><\/jats:sec>","DOI":"10.1111\/aos.15101","type":"journal-article","created":{"date-parts":[[2022,1,26]],"date-time":"2022-01-26T14:54:47Z","timestamp":1643208887000},"page":"788-796","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Topical noninvasive retinal drug delivery of a tyrosine kinase inhibitor: 3% cediranib maleate cyclodextrin nanoparticle eye drops in the rabbit eye"],"prefix":"10.1111","volume":"100","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2514-1323","authenticated-orcid":false,"given":"Laura","family":"Lorenzo\u2010Soler","sequence":"first","affiliation":[{"name":"Faculty of Medicine University of Iceland  Reykjav\u00edk Iceland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pitsiree","family":"Praphanwittaya","sequence":"additional","affiliation":[{"name":"Faculty of Pharmaceutical Sciences University of Iceland  Reykjav\u00edk Iceland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olof Birna","family":"Olafsdottir","sequence":"additional","affiliation":[{"name":"Faculty of Medicine University of Iceland  Reykjav\u00edk Iceland"},{"name":"Department of Ophthalmology Landspitali University Hospital  Reykjav\u00edk Iceland"},{"name":"Oculis ehf.  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