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Injectable polymer-nanoparticle hydrogel for the sustained intravitreal delivery of bimatoprost

View ORCID ProfileEmily L. Meany, View ORCID ProfileRoxanne Andaya, Shijia Tang, View ORCID ProfileCatherine M. Kasse, View ORCID ProfileReina N. Fuji, View ORCID ProfileAbigail K. Grosskopf, View ORCID ProfileAndrea l. d’Aquino, Joshua T. Bartoe, Ryan Ybarra, Amy Shelton, Zachary Pederson, Chloe Hu, Dennis Leung, Karthik Nagapudi, Savita Ubhayakar, Matthew Wright, Chun-Wan Yen, View ORCID ProfileEric A. Appel
doi: https://doi.org/10.1101/2022.09.08.507193
Emily L. Meany
1Department of Bioengineering, Stanford University, Stanford, CA 94305, USA
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Roxanne Andaya
2Genentech, Inc., 1 DNA Way, South San Francisco CA 94080 USA
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Shijia Tang
2Genentech, Inc., 1 DNA Way, South San Francisco CA 94080 USA
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Catherine M. Kasse
3Department of Materials Science & Engineering, Stanford University, Stanford, CA 94305, USA
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Reina N. Fuji
2Genentech, Inc., 1 DNA Way, South San Francisco CA 94080 USA
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Abigail K. Grosskopf
5Department of Chemical Engineering, Stanford University, Stanford, CA 94305, USA
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Andrea l. d’Aquino
3Department of Materials Science & Engineering, Stanford University, Stanford, CA 94305, USA
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Joshua T. Bartoe
4Northern Biomedical Research, Inc., 1210 Pontaluna Rd, Norton Shores, MI 49456, USA
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Ryan Ybarra
2Genentech, Inc., 1 DNA Way, South San Francisco CA 94080 USA
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Amy Shelton
2Genentech, Inc., 1 DNA Way, South San Francisco CA 94080 USA
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Zachary Pederson
2Genentech, Inc., 1 DNA Way, South San Francisco CA 94080 USA
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Chloe Hu
2Genentech, Inc., 1 DNA Way, South San Francisco CA 94080 USA
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Dennis Leung
2Genentech, Inc., 1 DNA Way, South San Francisco CA 94080 USA
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Karthik Nagapudi
2Genentech, Inc., 1 DNA Way, South San Francisco CA 94080 USA
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Savita Ubhayakar
2Genentech, Inc., 1 DNA Way, South San Francisco CA 94080 USA
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Matthew Wright
2Genentech, Inc., 1 DNA Way, South San Francisco CA 94080 USA
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Chun-Wan Yen
2Genentech, Inc., 1 DNA Way, South San Francisco CA 94080 USA
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  • For correspondence: eappel@stanford.edu yenc3@gene.com
Eric A. Appel
1Department of Bioengineering, Stanford University, Stanford, CA 94305, USA
3Department of Materials Science & Engineering, Stanford University, Stanford, CA 94305, USA
6ChEM-H Insitute, Stanford School of Medicine, Stanford, CA 94305, USA
7Woods Institute for the Environment, Stanford University, Stanford, CA 94305, USA
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  • For correspondence: eappel@stanford.edu yenc3@gene.com
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Abstract

Vision impairment resulting from chronic eye diseases, such as macular degeneration and glaucoma, severely impacts patients’ quality of life and poses an immense global financial burden. Current standard of care for such diseases includes daily eye drops or frequent intravitreal (ITV) injections, which are burdensome treatment modalities resulting in low patient compliance. There remains a growing need for easily administered long-acting delivery technologies for prolonging exposure of ocular therapeutics with each administration. Here, we deploy a supramolecular polymer-nanoparticle (PNP) hydrogel for ITV delivery of the glaucoma drug bimatoprost. PNP hydrogels are shear-thinning and self-healing, key properties for injectability, and enable slow release of molecular cargo in vitreous humor (VH) mimics. An in vivo study in New Zealand white rabbits demonstrated intravitreally injected PNP hydrogels form depots that degrade slowly over time, maintaining detectable levels of bimatoprost in the VH up to eight weeks following injection. Ophthalmic examinations and histopathology identified a mild foreign body response (FBR) to the hydrogel, characterized by rare clusters of foamy macrophages and giant cells associated with minimal, patchy fibroplasia. This work shows that PNP hydrogels exhibit numerous desirable traits for sustained drug delivery and further work will be necessary to optimize tolerability in the eye.

Competing Interest Statement

The authors have declared no competing interest.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted September 12, 2022.
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Injectable polymer-nanoparticle hydrogel for the sustained intravitreal delivery of bimatoprost
Emily L. Meany, Roxanne Andaya, Shijia Tang, Catherine M. Kasse, Reina N. Fuji, Abigail K. Grosskopf, Andrea l. d’Aquino, Joshua T. Bartoe, Ryan Ybarra, Amy Shelton, Zachary Pederson, Chloe Hu, Dennis Leung, Karthik Nagapudi, Savita Ubhayakar, Matthew Wright, Chun-Wan Yen, Eric A. Appel
bioRxiv 2022.09.08.507193; doi: https://doi.org/10.1101/2022.09.08.507193
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Injectable polymer-nanoparticle hydrogel for the sustained intravitreal delivery of bimatoprost
Emily L. Meany, Roxanne Andaya, Shijia Tang, Catherine M. Kasse, Reina N. Fuji, Abigail K. Grosskopf, Andrea l. d’Aquino, Joshua T. Bartoe, Ryan Ybarra, Amy Shelton, Zachary Pederson, Chloe Hu, Dennis Leung, Karthik Nagapudi, Savita Ubhayakar, Matthew Wright, Chun-Wan Yen, Eric A. Appel
bioRxiv 2022.09.08.507193; doi: https://doi.org/10.1101/2022.09.08.507193

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