April 2014
Volume 55, Issue 13
ARVO Annual Meeting Abstract  |   April 2014
Sustained Release of Bevacizumab from Hydrogel Depots for Intravitreal Injections
Author Affiliations & Notes
  • Rami F Elhayek
    R&D, Ocular Therapeutix, Bedford, MA
  • Amarpreet Sawhney
    R&D, Ocular Therapeutix, Bedford, MA
  • Peter Jarrett
    R&D, Ocular Therapeutix, Bedford, MA
  • Sarah Guedez
    R&D, Ocular Therapeutix, Bedford, MA
  • Courtney Rosales
    R&D, Ocular Therapeutix, Bedford, MA
  • Footnotes
    Commercial Relationships Rami Elhayek, OCULAR THERAPEUTIX INC (E); Amarpreet Sawhney, OCULAR THERAPEUTIX INC (E); Peter Jarrett, OCULAR THERAPEUTIX INC (E); Sarah Guedez, OCULAR THERAPEUTIX INC (E); Courtney Rosales, OCULAR THERAPEUTIX INC (E)
  • Footnotes
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Investigative Ophthalmology & Visual Science April 2014, Vol.55, 5264. doi:
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    • Get Citation

      Rami F Elhayek, Amarpreet Sawhney, Peter Jarrett, Sarah Guedez, Courtney Rosales; Sustained Release of Bevacizumab from Hydrogel Depots for Intravitreal Injections. Invest. Ophthalmol. Vis. Sci. 2014;55(13):5264.

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

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To evaluate the sustained release of bevacizumab from preformed hydrogel depots for intravitreal injections


Fine particles of bevacizumab were formulated in PEG hydrogels to form injectable depots. The depots were examined in vitro for sustained release under accelerated conditions in TBS (pH 8.0 and 8.5) and real-time conditions in PBS (pH 7.2) at 37°C. Accelerated and real-time in vitro release was explored to determine release profiles and aggregation (by SEC) as a result of the gradual hydrogel degradation. In vivo assessment was conducted in rabbit eyes (8 eyes, 10µl depot volume) for up to 8 weeks using ocular clinical observations and Optical Coherence Tomography (OCT)


Release profiles (Figure 1(a)) show the effect of hydrogel degradation time on sustained release of bevacizumab under accelerated and real-time conditions. The real time in vitro release profile showed a controlled low burst (2.5%) and release up to 4 weeks. The accelerated profile demonstrated a 38x acceleration factor (pH8.5) and 19x (pH8.0), high total percent recovery (>90%) and good correlation of release rate to pH (Figure 1(b)), indicating gel hydrolysis control of drug release. Minimal high molecular weight species were observed, indicating low aggregation. OCT images (Figure 2) for placebo and bevacizumab loaded depots indicate good biocompatibility with vitreal and retinal tissues. No retinal abnormalities or detachments were noted for up to 8 weeks. Clinical ocular observations using the McDonald-Shadduck scoring system were also normal


Monoclonal antibody fragments and fusion proteins have been designed to inhibit vascular endothelial growth factors (VEGF) for treatment of posterior segment diseases such as age-related macular degeneration (AMD) and diabetic macular edema (DME). Although bevacizumab is not approved for ophthalmic use, it has been clinically investigated for safety and efficacy as an affordable alternative to current treatments. The frequency of the intravitreal injections is still the major challenge to overcome in treating posterior ocular diseases to prevent vision loss or even gain visual acuity. The ability to sustain the release of bevacizumab for 4-6 months from hydrogel depots provides a technology platform for use with anti-VEGFs to decrease the frequency of intravitreal injections and reduce the risk of side effects associated with repeated injections

Keywords: 763 vitreous • 748 vascular endothelial growth factor • 412 age-related macular degeneration  

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