June 2015
Volume 56, Issue 7
ARVO Annual Meeting Abstract  |   June 2015
Author Affiliations & Notes
  • Gary Owens
    Envisia Therapeutics, Durham, NC
  • Stuart Williams
    Envisia Therapeutics, Durham, NC
  • Kevin Herlihy
    Envisia Therapeutics, Durham, NC
  • Janet Tully
    Envisia Therapeutics, Durham, NC
  • Rozemarijn S Verhoeven
    Envisia Therapeutics, Durham, NC
  • Tomas Navratil
    Envisia Therapeutics, Durham, NC
  • Benjamin Maynor
    Envisia Therapeutics, Durham, NC
  • Benjamin Yerxa
    Envisia Therapeutics, Durham, NC
  • Footnotes
    Commercial Relationships Gary Owens, Envisia Therapeutics (E); Stuart Williams, Envisia Therapeutics (E); Kevin Herlihy, Envisia Therapeutics (E); Janet Tully, Envisia Therapeutics (E); Rozemarijn Verhoeven, Envisia Therapeutics (E); Tomas Navratil, Envisia Therapeutics (E); Benjamin Maynor, Envisia Therapeutics (E); Benjamin Yerxa, Envisia Therapeutics (E)
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2015, Vol.56, 236. doi:
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      Gary Owens, Stuart Williams, Kevin Herlihy, Janet Tully, Rozemarijn S Verhoeven, Tomas Navratil, Benjamin Maynor, Benjamin Yerxa; ESTABLISHING IN VIVO TO IN VITRO CORRELATIONS FOR THE RATE OF RELEASE OF BEVACIZUMAB FROM EXTENDED RELEASE FORMULATIONS. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):236.

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

  • Supplements

Extended release of anti-Vascular Endothelial Growth Factor (VEGF) monoclonal antibodies (mAb) represents one of the most coveted future approaches to the treatment of Age-Related Macular Degeneration (AMD), Diabetic Macular Edema (DME), and Retinal Vein Occlusion (RVO). We demonstrate the ability to produce ocular implants for the sustained release of bevacizumab by combining solid state protein micro particles with sustained release hydrogel matrices.


We fabricated size and shape specific PRINT protein particles that are uniformly distributed and embedded in sustained release hydrogel formulations. Solid-state bevacizumab particles were characterized with Scanning Electron Microscopy (SEM) for morphology, Size Exclusion Chromatography (SEC) for monomeric content and VEGF ELISA for activity. Formulations were down-selected based on specific hydrogel parameters and in vitro rate of release was monitored to assess daily rate of release. In vivo, formulation daily rate of release and pharmacokinetics were monitored in Dutch Belted and New Zealand White rabbits and compared to in vitro release data to determine the in vitro / in vivo rate of release relationship


Maximum bevacizumab dose per implant and targeted duration of release was accomplished by optimization of particle formulation and implant loading. Implant formulations characterized by duration of release of 50 days in vitro (i.e. 100% of bevacizumab was released over 50 days) were assed in an in vivo rabbit model. These implants contained 15% of residual bevacizumab at 80 days post injection compared to the starting bevacizumab implant dose. In vitro assays were found to be qualitatively predictive of in vivo rate of release as faster releasing formulations in vitro also released faster in vivo when compared to longer releasing formulations. Active bevacizumab was able to be measured in the vitreous and plasma at select time points.


We have demonstrated a unique formulation approach for sustained release of anti-VEGF agent bevacizumab, combining precision protein particle fabrication with sustained release polymers. These studies indicate that rate of release in vitro is qualitatively predictive of in vivo daily rate of release, allowing one to rationally design bevacizumab formulations to achieve an extended treatment profile for AMD  


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