April 2014
Volume 55, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2014
Photocurable Hydrogel Implants for the Extended Release of Bevacizumab for the Treatment of Age Related Macular Degeneration
Author Affiliations & Notes
  • Stuart Williams
    Envisia Therapeutics, Durham, NC
  • Kevin Herlihy
    Envisia Therapeutics, Durham, NC
  • Gary Owens
    Envisia Therapeutics, Durham, NC
  • John Savage
    Envisia Therapeutics, Durham, NC
  • Lindsay Gardner
    Envisia Therapeutics, Durham, NC
  • Janet Tully
    Envisia Therapeutics, Durham, NC
  • Benjamin Maynor
    Envisia Therapeutics, Durham, NC
    Liquidia Technologies, Durham, NC
  • Tomas Navratil
    Envisia Therapeutics, Durham, NC
    Liquidia Technologies, Durham, NC
  • Benjamin R Yerxa
    Envisia Therapeutics, Durham, NC
    Liquidia Technologies, Durham, NC
  • Footnotes
    Commercial Relationships Stuart Williams, Envisia Therapeutics (E); Kevin Herlihy, Envisia Therapeutics (E); Gary Owens, Envisia Therapeutics (E); John Savage, Envisia Therapeutics (E); Lindsay Gardner, Envisia Therapeutics (E); Janet Tully, Envisia Therapeutics (E); Benjamin Maynor, Envisia Therapeutics (E); Tomas Navratil, Envisia Therapeutics (E); Benjamin Yerxa, Envisia Therapeutics (E)
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science April 2014, Vol.55, 471. doi:https://doi.org/
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    • Get Citation

      Stuart Williams, Kevin Herlihy, Gary Owens, John Savage, Lindsay Gardner, Janet Tully, Benjamin Maynor, Tomas Navratil, Benjamin R Yerxa; Photocurable Hydrogel Implants for the Extended Release of Bevacizumab for the Treatment of Age Related Macular Degeneration. Invest. Ophthalmol. Vis. Sci. 2014;55(13):471. doi: https://doi.org/.

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

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Abstract
 
Purpose
 

As a means to improve treatment of RVO, AMD, and DME, one goal of current therapy is to extend the vitreal half-life of anti-VEGF proteins and peptides. Photocurable hydrogel matrices, in particular, are a promising class of materials for extended intravitreal release of proteins. Herein, we demonstrate the ability to produce extended release ocular implants of bevacizumab, an anti-VEGF monoclonal antibody, by embedding solid state protein microparticles into photocurable hydrogel matrices. Release rate was controlled by hydrogel formulation with linear profiles being obtained.

 
Methods
 

1μm x 1μm preformed PRINT cylinders composed of protein and protective excipients were fabricated using the PRINT® process. The PRINT microparticles were then dispersed in a solution of photocurable PEG, water, and photoinitiator. The resulting suspension was photochemically cured to a pre-formed size. The in vitro release rate of protein was monitored in PBS at 37°C using ELISA. The morphology of the implants was characterized with electron microscopy to determine the distribution of protein microparticles within the implants.

 
Results
 

Implant size and shape was controlled using a preformed template. After photochemical curing, the PRINT microparticles were observed to be uniformly distributed in a solid state hydrogel matrix (Fig 1). In vitro release measurements demonstrate near zero-order release of active protein for a period of over 90 days (Fig 1).

 
Conclusions
 

PRINT technology allows for the design of solid state protein microparticles that can be incorporated into hydrogel implants with zero-order release profiles. Protein release can be tuned to be linear and independent of degradation rate. Design and manufacturing of these types of extended-release systems potentially allow reduced-frequency dosing of anti-VEGF therapies for treatment of retinal diseases.

 
 
Figure 1) Bevacizumab PRINT microparticles embedded in a hydrogel implant (left), in-vitro release curve up to day 97 from the hydrogel implants ELISA (right).
 
Figure 1) Bevacizumab PRINT microparticles embedded in a hydrogel implant (left), in-vitro release curve up to day 97 from the hydrogel implants ELISA (right).
 
Keywords: 412 age-related macular degeneration • 748 vascular endothelial growth factor  
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