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Gary Owens, Melissa Sandahl, Melissa Hernandez, Andres Garcia, Stuart Williams, Tomas Navratil, Rhett Schiffman; Extended Release of anti-VEGF Biologics from Biodegradable Hydrogel Implants for the Treatment of Age Related Macular Degeneration. Invest. Ophthalmol. Vis. Sci. 2016;57(12):527. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Decreasing the frequency of intravitreal injections of standard anti-VEGF therapies by means of an extended release formulations, would not only result in reduced burden to patients but may also result in improved clinical outcomes in the treatment of age-related macular degeneration (AMD), diabetic macular edema (DME), and retinal vein occlusion (RVO). Development of such extended release therapies has proven challenging due to the limited physicochemical stability of anti-VEGF biologics. Herein, we demonstrate the ability to produce extended release intravitreal implants for the release of anti-VEGF biologics by encapsulating solid state protein microparticles in biodegradable, extended release hydrogel matrices.
Micronized solid state protein particles were embedded uniformly throughout the hydrogel implant. Hydrogels with various degradation rates were studied. In-vitro release rate of the biologics from the hydrogel matrix and overall duration of action was monitored in 1X PBS pH 7.4 at 37 C, using total protein assays and a VEGF ELISA. Additional physicochemical characterization of protein released over several months was performed to assess protein stability by size exclusion chromatography and bioactivity by surface plasmon resonance.
In vitro studies demonstrate complete release of protein over several months at therapeutically relevant levels. Physicochemical characterization of ongoing in vitro release studies indicate that the released protein is comparable to initial starting material with respect to functionality, binding kinetics and monomer content. These data support advancing implant formulations in vivo for pharmacokinetic and tolerability evaluation in non-human primates.
We have demonstrated the ability to formulate biodegradable intravitreal implants with tunable, reproducible release kinetics of anti-VEGF biologics. Our in vitro data establishes proof of concept for multi-month extended release of active anti-VEGF biologics, potentially bypassing the need for monthly intravitreal injections.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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