April 2014
Volume 55, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2014
Extended Release of Microfabricated Protein Particles from Biodegradable Hydrogel Implants for the Treatment of Age Related Macular Degeneration
Author Affiliations & Notes
  • Kevin Patrick Herlihy
    Envisia Therapeutics, Morrisville, NC
  • Stuart Williams
    Envisia Therapeutics, Morrisville, NC
  • Gary Owens
    Envisia Therapeutics, Morrisville, NC
  • John Savage
    Envisia Therapeutics, Morrisville, NC
  • Lindsay Gardner
    Envisia Therapeutics, Morrisville, NC
  • RiLee Robeson
    Envisia Therapeutics, Morrisville, NC
  • Benjamin Maynor
    Envisia Therapeutics, Morrisville, NC
  • Tomas Navratil
    Envisia Therapeutics, Morrisville, NC
  • Brian C Gilger
    Envisia Therapeutics, Morrisville, NC
  • Benjamin R Yerxa
    Envisia Therapeutics, Morrisville, NC
  • Footnotes
    Commercial Relationships Kevin Herlihy, Envisia Therapeutics (E); Stuart Williams, Envisia Therapeutics (E); Gary Owens, Envisia Therapeutics (E); John Savage, Envisia Therapeutics (E); Lindsay Gardner, Envisia Therapeutics (E); RiLee Robeson, Envisia Therapeutics (E); Benjamin Maynor, Envisia Therapeutics (E); Tomas Navratil, Envisia Therapeutics (E); Brian Gilger, Envisia Therapeutics (E); Benjamin Yerxa, Envisia Therapeutics (E)
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science April 2014, Vol.55, 1960. doi:
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      Kevin Patrick Herlihy, Stuart Williams, Gary Owens, John Savage, Lindsay Gardner, RiLee Robeson, Benjamin Maynor, Tomas Navratil, Brian C Gilger, Benjamin R Yerxa; Extended Release of Microfabricated Protein Particles from Biodegradable Hydrogel Implants for the Treatment of Age Related Macular Degeneration. Invest. Ophthalmol. Vis. Sci. 2014;55(13):1960.

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

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Abstract
 
Purpose
 

Extended release implants of anti-VEGF therapies may reduce burden on patients, but development of such therapies is a challenge due to fragile nature of anti-VEGF biologics. Biodegradable hydrogel matrices are a promising class of release matrix for proteins. Herein, we demonstrate the ability to produce extended release ocular implants of bevacizumab by combining solid state protein microparticles formulated using PRINT® technology with extended release hydrogel matrices.

 
Methods
 

Monodisperse 1μm PRINT cylinders composed of excipients and protein were created using the PRINT process. Microparticles were uniformly dispersed throughout the hydrogel implant. Hydrogels with various structures and degradation rates were studied. Physicochemical characterization of the implants was performed to evaluate the overall mass uniformity, content uniformity, and protein binding activity across individual implants. In vitro release of protein from the implants in PBS at 37°C was observed. Safety, tolerability, and release were monitored in vivo.

 
Results
 

Envisia’s PRINT technology provides the unique ability to impart control over size and shape (Figure 1) of protein particles, with retention of biological activity. Monodisperse bevacizumab particles allowed for uniform distribution of protein-rich microphases within hydrogel implants. Parameters such as hydrogel mesh size and degradation kinetics were also demonstrated to change bevacizumab release rate. In vitro release studies demonstrate near 100% release of active protein with complete release ranging from 1 day to greater than 25 days.

 
Conclusions
 

PRINT technology allows for the design of solid state protein microparticles of uniform size and shape that can be incorporated into a variety of hydrogel implants with tunable, reproducible release kinetics. Design and manufacturing of these types of extended-release systems will potentially allow reduced-frequency dosing of anti-VEGF therapies for treatment of AMD.

 
 
Figure 1) Bevacizumab PRINT microparticles created using PRINT technology (left), in vitro release curves from two implant formulations (right).
 
Figure 1) Bevacizumab PRINT microparticles created using PRINT technology (left), in vitro release curves from two implant formulations (right).
 
Keywords: 412 age-related macular degeneration • 748 vascular endothelial growth factor • 763 vitreous  
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