June 2015
Volume 56, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2015
Pharmacokinetics of Bevacizumab Sustained Release from Intravitreal Hydrogel Depots in a Rabbit Model Compared to a single Avastin Dose
Author Affiliations & Notes
  • Rami F Elhayek
    R&D, Ocular Therapeutix, Bedford, MA
  • Peter K Jarrett
    R&D, Ocular Therapeutix, Bedford, MA
  • Amar Sawhney
    R&D, Ocular Therapeutix, Bedford, MA
  • Arthur Driscoll
    R&D, Ocular Therapeutix, Bedford, MA
  • Timothy S. Jarrett
    R&D, Ocular Therapeutix, Bedford, MA
  • Courtney Rosales
    R&D, Ocular Therapeutix, Bedford, MA
  • Andrew Vanslette
    R&D, Ocular Therapeutix, Bedford, MA
  • Charles D Blizzard
    R&D, Ocular Therapeutix, Bedford, MA
  • sarah guedez
    R&D, Ocular Therapeutix, Bedford, MA
  • Footnotes
    Commercial Relationships Rami Elhayek, OCULAR THERAPEUTIX INC (E); Peter Jarrett, OCULAR THERAPEUTIX (E); Amar Sawhney, OCULAR THERAPEUTIX (E); Arthur Driscoll, OCULAR THERAPEUTIX (E); Timothy Jarrett, OCULAR THERAPEUTIX (E); Courtney Rosales, OCULAR THERAPEUTIX (E); Andrew Vanslette, OCULAR THERAPEUTIX (E); Charles Blizzard, OCULAR THERAPEUTIX (E); sarah guedez, OCULAR THERAPEUTIX (E)
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2015, Vol.56, 1522. doi:
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      Rami F Elhayek, Peter K Jarrett, Amar Sawhney, Arthur Driscoll, Timothy S. Jarrett, Courtney Rosales, Andrew Vanslette, Charles D Blizzard, sarah guedez; Pharmacokinetics of Bevacizumab Sustained Release from Intravitreal Hydrogel Depots in a Rabbit Model Compared to a single Avastin Dose. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):1522.

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

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Abstract
 
Purpose
 

To determine the pharmacokinetics profile of a sustained release bevacizumab (bev) intravitreal (IVT) hydrogel depot (OTX-BI) compared to a single dose Avastin IVT injection

 
Methods
 

Fine particles of bevacizumab were formulated to form OTX-BI hydrogel depots. Sustained release OTX-BI depots (50ul; 2.5mg bev) were intravitreally injected (27G ½ in. needle) in rabbit eyes to compare tissue concentrations (Plasma, vitreous humor, retina and choroid) with rabbit eyes injected with a single Avastin injection (50ul; 1.25mg ). Rabbits were sacrificed at several time points and tissues were harvested, separated then analyzed by ELISA (200-800-AVG) assay after kit qualification in blank matrices spiked with Avastin. In vivo assessment of tissue level and IOP was conducted at each time point (1, 14 and 28 days; n=6)

 
Results
 

All eyes were clinically examined (McDonald-Shadduck) and noted to be normal during the course of the study with no signs of inflammation or changes in intraocular pressure (Table 1). Tissue concentrations in plasma, vitreous humor, retina and choroid were determined using ELISA. Results reported in Table 2 indicated that while Avastin tissue levels decreased over time, OTX-BI exhibited sustained tissue levels through 28 days

 
Conclusions
 

Sustained release of bevacizumab was successfully demonstrated in an intravitreal rabbit model. Tissue levels were sustained through 28 days from OTX-BI depot. By contrast, tissue level from a single Avastin injection quickly decayed to undetectable levels by 28 days. The OTX-BI depot is designed to sustain the release of bevacizumab for 4-6 months. These findings provide a new technology platform to sustain the release of bevacizumab from biocompatible, bioresorbable intravitreal hydrogel depots. Sustained anti-VEGF release may decrease the frequency of intravitreal injections and reduce the risk of side effects. 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  

 

 
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