July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
Poly (oligo ethylene glycol methacrylate) hydrogels for controlled release of protein-based therapeutics
Author Affiliations & Notes
  • Ben B Muirhead
    Chemical Engineering, McMaster University, Hamilton, Ontario, Canada
  • Emily Anne Hicks
    Chemical Engineering, McMaster University, Hamilton, Ontario, Canada
  • Heather Sheardown
    Chemical Engineering, McMaster University, Hamilton, Ontario, Canada
  • Footnotes
    Commercial Relationships   Ben Muirhead, None; Emily Anne Hicks, None; Heather Sheardown, None
  • Footnotes
    Support  none
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 3381. doi:
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      Ben B Muirhead, Emily Anne Hicks, Heather Sheardown; Poly (oligo ethylene glycol methacrylate) hydrogels for controlled release of protein-based therapeutics. Invest. Ophthalmol. Vis. Sci. 2019;60(9):3381.

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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose : Collectively, neovascularative pathologies of the retina represent a leading cause of vision impairment and blindness. Protein-based anti-VEGF drugs have radically improved this clinical landscape. 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. This hydrogel is injected as a liquid and form a gel inside the vitreous, creating a minimally invasive drug depot designed to deliver anti-VEGF drugs.

Methods : Poly (oligo ethylene glycol methacrylate) (POEGMA) polymers were synthesized using free radical co-polymerization of various lengths 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. Avastin 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 more than 6 months in vitro. A monthly challenge using the CNV laser is used to demonstrate the continued activity of trapped drug over a 6 month time horizon.

Results : 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. Avastin has been encapsulated within these depots and has demonstrated clinically useful release kinetics over more than 6 months. Using a laser induced rat CNV model, POEGMA gels were evaluated for efficacy in a CNV disease model and showed significantly smaller lesions after laser challenges when Avastin-loaded POEGMA gels were present.

Conclusions : POEGMA hydrogels offer a solution to the difficult problem of protein delivery to the back of the eye. The implantation of POEGMA into the vitreous resulted in excellent tolerability and biocompatibility. A CNV model has been adapted to test the ability of these implants to release therapeutic concentrations of Avasin over at least 6 months.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.



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