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The PK-Eye: A Novel In Vitro Ocular Flow Model for Use in Preclinical Drug Development

Awwad, S; Lockwood, A; Brocchini, S; Khaw, PT; (2015) The PK-Eye: A Novel In Vitro Ocular Flow Model for Use in Preclinical Drug Development. Journal of Pharmaceutical Sciences , 104 (10) pp. 3330-3342. 10.1002/jps.24480. Green open access

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Abstract

A 2-compartment in vitro eye flow model has been developed to estimate ocular drug clearance by the anterior aqueous outflow pathway. The model is designed to accelerate the development of longer-acting ophthalmic therapeutics. Dye studies show aqueous flow is necessary for a molecule injected into the vitreous cavity to clear from the model. The clearance times of proteins can be estimated by collecting the aqueous outflow, which was first conducted with bevacizumab using phosphate-buffered saline in the vitreous cavity. A simulated vitreous solution was then used and ranibizumab (0.5 mg) displayed a clearance time of 8.1 ± 3.1 days, which is comparable to that observed in humans. The model can estimate drug release from implants or the dissolution of suspensions as a first step in their clearance mechanism, which will be the rate-limiting step for the overall resident time of a candidate dosage form in the vitreous. A suspension of triamcinolone acetonide (Kenalog®) (4.0 mg) displayed clearance times spanning 26–28 days. These results indicate that the model can be used to determine in vitro-in vivo correlations in preclinical studies to develop long-lasting therapeutics to treat blinding diseases at the back of the eye.

Type: Article
Title: The PK-Eye: A Novel In Vitro Ocular Flow Model for Use in Preclinical Drug Development
Open access status: An open access version is available from UCL Discovery
DOI: 10.1002/jps.24480
Publisher version: https://doi.org/10.1002/jps.24480
Language: English
Additional information: This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
Keywords: Intraocular fluid flow, in vitro/in vivo correlations (IVIVC), in vitro model, pharmacokinetics, proteins, protein delivery, intraocular drug suspension, ocular drug delivery, intravitreal injection
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy > Pharmaceutics
URI: https://discovery.ucl.ac.uk/id/eprint/10070102
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