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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.
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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.
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.
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.
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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