June 2015
Volume 56, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2015
In-Vitro Release of Bevacizumab from Hydrogel-based Drug Delivery Systems
Author Affiliations & Notes
  • Janet Tully
    Envisia Therapeutics, Morrisville, NC
  • Stuart Williams
    Envisia Therapeutics, Morrisville, NC
  • Kevin Herlihy
    Envisia Therapeutics, Morrisville, NC
  • Gary Owens
    Envisia Therapeutics, Morrisville, NC
  • Gabe Fawcett
    Envisia Therapeutics, Morrisville, NC
  • Nicole Meyer
    Envisia Therapeutics, Morrisville, NC
  • Tomas Navratil
    Envisia Therapeutics, Morrisville, NC
  • Benjamin Maynor
    Envisia Therapeutics, Morrisville, NC
  • Benjamin Yerxa
    Envisia Therapeutics, Morrisville, NC
  • Footnotes
    Commercial Relationships Janet Tully, Envisia Therapeutics (E); Stuart Williams, Envisia Th (E); Kevin Herlihy, Envisia Therapeutics (E); Gary Owens, Envisia Therapeutics (E); Gabe Fawcett, Envisia Therapeutics (E); Nicole Meyer, Envisia Therapeutics (E); Tomas Navratil, Envisia Therapeutics (E), Liquidia Technologies (E); Benjamin Maynor, Envisia Therapeutics (E); Benjamin Yerxa, Envisia Therapeutics (E)
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2015, Vol.56, 222. doi:https://doi.org/
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      Janet Tully, Stuart Williams, Kevin Herlihy, Gary Owens, Gabe Fawcett, Nicole Meyer, Tomas Navratil, Benjamin Maynor, Benjamin Yerxa; In-Vitro Release of Bevacizumab from Hydrogel-based Drug Delivery Systems. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):222. 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 Retinal Vein Occlusion (RVO), Age-related Macular Degeneration (AMD), and Diabetic Macular Edema (DME), one goal of current therapy is to extend the therapeutically relevant vitreous concentrations of anti-Vascular Endothelial Growth Factor (anti-VEGF) proteins and peptides. Hydrogel matrices, in particular, are a promising class of materials for the extended intravitreal release of proteins. Herein, we demonstrate the ability to produce extended release ocular implants containing bevacizumab, an anti-VEGF monoclonal antibody, by embedding solid state protein microparticles in hydrogel matrices.

 
Methods
 

Protein was encapsulated into sustained release PRINT® implants by fabricating solid state particles containing bevacizumab. 1 µm x 1 µm preformed cylinders composed of protein and protective excipients were fabricated using the PRINT process. The microparticles were then dispersed in a solution of PEG that was chemically cross-linked to form solid state gels embedded with protein microparticles. Bevacizumab release was characterized in vitro in 1X PBS pH 7.4 at 37˚C, using total protein assays and a VEGF ELISA.

 
Results
 

Multi-month release of active bevacizumab was achieved from the implant drug delivery system. Using hydrogel blends we successfully controlled the rate of release of bevacizumab with total release of bevacizumab varying from 25 to greater than 200 days. Maximum dose and delivery time was accomplished by optimization of particle formulation and implant loading.

 
Conclusions
 

We have demonstrated a unique formulation approach for sustained release, combining precision protein particle fabrication with sustained release polymers. Our in vitro data establishes proof of concept for multi-month release of active anti-VEGF biologics.  

 
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