Velentza-Almpani, Angeliki;
Ibeanu, Nkiruka;
Liu, Tianyang;
Redhead, Christopher;
Tee Khaw, Peng;
Brocchini, Steve;
Awwad, Sahar;
(2022)
Effects of Flow Hydrodynamics and Eye Movements on Intraocular Drug Clearance.
Pharmaceutics
, 14
(6)
, Article 1267. 10.3390/pharmaceutics14061267.
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Abstract
New in vitro prototypes (PK-Eye™) were tested with and without eye movement to understand diffusion and convection effects on intraocular clearance. Port placement in front ((i) ciliary inflow model) and behind the model lens ((ii) posterior inflow model) was used to study bevacizumab (1.25 mg/50 µL) and dexamethasone (0.1 mg/100 µL) in phosphate-buffered saline (PBS, pH 7.4) and simulated vitreal fluid (SVF). Dexamethasone was studied in a (iii) retinal-choroid-sclera (RCS) outflow model (with ciliary inflow and two outflow pathways). Ciliary vs. posterior inflow placement did not affect the half-life for dexamethasone at 2.0 µL/min using PBS (4.7 days vs. 4.8 days) and SVF (4.9 days with ciliary inflow), but it did decrease the half-life for bevacizumab in PBS (20.4 days vs. 2.4 days) and SVF (19.2 days vs. 10.8 days). Eye movement only affected the half-life of dexamethasone in both media. Dexamethasone in the RCS model showed approximately 20% and 75% clearance from the RCS and anterior outflows, respectively. The half-life of the protein was comparable to human data in the posterior inflow model. Shorter half-life values for a protein in a ciliary inflow model can be achieved with other eye movements. The RCS flow model with eye movement was comparable to human half-life data for dexamethasone.
| Type: | Article |
|---|---|
| Title: | Effects of Flow Hydrodynamics and Eye Movements on Intraocular Drug Clearance |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.3390/pharmaceutics14061267 |
| Publisher version: | https://doi.org/10.3390/pharmaceutics14061267 |
| Language: | English |
| Additional information: | This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third-party material in this article are included in the Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
| Keywords: | Ocular; pharmacokinetics; pharmaceutical modelling; convection; diffusion; saccades; automation; microfluidics |
| UCL classification: | 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 UCL 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 > Pharmaceutics UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10150657 |
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