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Ben B Muirhead, Heather Sheardown, Emilia Paron; POEGMA Hydrogels as a Posterior Depot for Controlled Release of Protein-Based Therapeutics. Invest. Ophthalmol. Vis. Sci. 2018;59(9):4456.
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© ARVO (1962-2015); The Authors (2016-present)
Less than a decade ago, the goal of treatment for progressive neovascularative pathologies of the retina was, at best, to slow progression of these diseases. New anti-VEGF drugs, including Eylea, have radically improved this landscape, allowing in some cases reversal of these previously blinding diseases. However, the resultant burden placed on the healthcare system is enormous, and every injection comes with a small risk of complication, which compounds due to frequency.A novel, in situ gelling, polymeric hydrogel material designed specifically to entrap proteins and release them over long periods of time has been created. These hydrogels are injected as a liquid and form gels inside the vitreous, creating a drug depot of any size.
Poly (oligo ethylene glycol methacrylate) (POEGMA) polymers were synthesized using free radical co-polymerization of oligo (ethylene glycol) methacrylate monomers, and functional monomers acrylic acid (AA) or N-(2,2 -dimethoxy ethyl) methacrylamide to impart hydrazide or aldehyde functionality.Norway Brown rats are induced with choroidal neovascularisation (CNV) using the Phoneix Micron IV laser CNV system. CNV is characterised using OCT and fluorescein angiography. Elyea is mixed with gel precursors and injected though a 30g syringe into the vitreous. Eylea trapped within the forming gel has shown continuous release for months in vitro. A monthly rechallenge using the CNV laser is used to demonstrate the continued activity of trapped drug over a 6 month time horizon.
In situ gelling hydrogels optimised for the posterior segment protein delivery have been created. These candidate materials have been injected into the vitreous and have shown no deleterious immunological effect. Eylea has been encapsulated within these depots and has shown constant release over 35 days, with no indication of slowing. Using a laser induced rat CNV model, POEGMA gels are evaluated for efficacy in a relevant disease model.
POEGMA hydrogels offer a solution to the difficult problem of protein delivery to the back of the eye. These materials can be fabricated to have zero swelling properties and be optically transparent. The successful implantation of the POEGMA into the vitreous resulted in excellent tolerability. A CNV model has been adapted to test the ability of these implants to release therapeutic concentrations of Eylea over 6 months.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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