eprintid: 10070102 rev_number: 19 eprint_status: archive userid: 608 dir: disk0/10/07/01/02 datestamp: 2019-03-12 16:01:31 lastmod: 2021-09-26 22:50:15 status_changed: 2019-03-12 16:01:31 type: article metadata_visibility: show creators_name: Awwad, S creators_name: Lockwood, A creators_name: Brocchini, S creators_name: Khaw, PT title: The PK-Eye: A Novel In Vitro Ocular Flow Model for Use in Preclinical Drug Development ispublished: pub divisions: UCL divisions: B02 divisions: C07 divisions: D08 divisions: C08 divisions: D10 divisions: G08 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 note: 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. 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. date: 2015-10 date_type: published publisher: WILEY-BLACKWELL official_url: https://doi.org/10.1002/jps.24480 oa_status: green full_text_type: pub language: eng primo: open primo_central: open_green article_type_text: Article verified: verified_manual elements_id: 1055204 doi: 10.1002/jps.24480 language_elements: English lyricists_name: Brocchini, Steve lyricists_name: Khaw, Peggy lyricists_name: Khaw, Peng Tee lyricists_name: Lockwood, Alastair lyricists_name: Shiekh Hassan Awwad, Sahar lyricists_id: SBROC55 lyricists_id: PKHAW35 lyricists_id: PTKHA24 lyricists_id: ALOCK61 lyricists_id: SAWWA21 actors_name: Novi, Maya actors_id: MNOVI52 actors_role: owner full_text_status: public publication: Journal of Pharmaceutical Sciences volume: 104 number: 10 pagerange: 3330-3342 pages: 13 issn: 1520-6017 citation: 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 <https://doi.org/10.1002/jps.24480>. Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/10070102/1/AWWAD_1-s2.0-S0022354916301186-main.pdf