Topical noninvasive retinal drug delivery of a tyrosine kinase inhibitor: 3% cediranib maleate cyclodextrin nanoparticle eye drops in the rabbit eye.
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
Olafsdottir, Olof Birna
Kristinsdottir, Iris Myrdal
Asgrimsdottir, Gudrun Marta
MetadataShow full item record
CitationLorenzo-Soler L, Praphanwittaya P, Olafsdottir OB, et al. Topical noninvasive retinal drug delivery of a tyrosine kinase inhibitor: 3% cediranib maleate cyclodextrin nanoparticle eye drops in the rabbit eye [published online ahead of print, 2022 Jan 26]. Acta Ophthalmol. 2022;10.1111/aos.15101. doi:10.1111/aos.15101
AbstractPurpose: Tyrosine kinase inhibitors inhibit VEGF receptors. If delivered to the retina, they might inhibit oedema and neovascularization such as in age-related macular degeneration and diabetic retinopathy. The aim of this study was to formulate cediranib maleate, a potent VEGF inhibitor, as γ-cyclodextrin nanoparticle eye drops and measure the retinal delivery and overall ocular pharmacokinetics after a single-dose administration in rabbits. Methods: A novel formulation technology with 3% cediranib maleate as γ-cyclodextrin micro-suspension was prepared by autoclaving method. Suitable stabilizers were tested for heat-stable 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 hr after administration. Results: γ-cyclodextrin formed complex with cediranib maleate. The formation of γ-cyclodextrin 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 ± 460 nM (mean ± SD) in the retina and 10 ± 6 nM in the vitreous humour. Conclusions: Cediranib maleate in γ-cyclodextrin 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 nM IC50 value reported for the VEGF type-II receptor and thus, presumably, above therapeutic level. These results suggest that γ-cyclodextrin-based cediranib maleate eye drops deliver effective drug concentrations to the retina in rabbits after a single-dose administration. Keywords: cediranib; cyclodextrins; drug delivery; in vivo; neovascularization; pharmacokinetics; topical administration.
DescriptionTo access publisher's full text version of this article click on the hyperlink below
Rights© 2022 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.
- Angiotensin Receptor Blockers in cyclodextrin nanoparticle eye drops: Ocular pharmacokinetics and pharmacologic effect on intraocular pressure.
- Authors: Lorenzo-Soler L, Olafsdottir OB, Garhöfer G, Jansook P, Kristinsdottir IM, Tan A, Loftsson T, Stefansson E
- Issue date: 2021 Jun
- Bio-Distribution and Pharmacokinetics of Topically Administered γ-Cyclodextrin Based Eye Drops in Rabbits.
- Authors: Kallab M, Schuetzenberger K, Hommer N, Schäfer BJ, Schmidl D, Bergmeister H, Zeitlinger M, Tan A, Jansook P, Loftsson T, Stefansson E, Garhöfer G
- Issue date: 2021 May 18
- A Novel Eye Drop Formulation for Potential Treatment of Neovascular Age-Related Macular Degeneration.
- Authors: Huang WC, Cheng F, Chen CC, Kuo PH, Wang YJ, Yin SC, Tu CM, Wu MH, Wang WY, Chen SE
- Issue date: 2021 Dec 1
- Cyclodextrin microparticles for drug delivery to the posterior segment of the eye: aqueous dexamethasone eye drops.
- Authors: Loftsson T, Hreinsdóttir D, Stefánsson E
- Issue date: 2007 May
- Aqueous eye drops containing drug/cyclodextrin nanoparticles deliver therapeutic drug concentrations to both anterior and posterior segment.
- Authors: Loftsson T, Stefánsson E
- Issue date: 2022 Feb