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John Savage, Kevin Patrick Herlihy, Gary Owens, Jeremy Hansen, RiLee Robeson, Benjamin Maynor, Tomas Navratil, Brian C Gilger, Benjamin R Yerxa; Bioerodable Hydrophobic Intravitreal Implants for the Extended Release of Bevacizumab for Age Related Macular Degeneration. Invest. Ophthalmol. Vis. Sci. 2014;55(13):1951.
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Extended release of anti-VEGF drugs for the treatment of Age-Related Macular Degeneration (AMD) from a bioerodable depot is an attractive alternative to currently formulated products. Current products in development employ non-degradable depots which either need to be removed by surgery or remain in situ. We report on the formulation of hydrophobic implants for intravitreal injection containing the solid state protein bevacizumab with tunable drug release profile and implant biodegradability.
Using the PRINT® technology, we fabricated monodisperse micrometer size protein particles (Fig. 1a, inset). PRINT bevacizumab particles were homogeneously embedded into hydrophobic, erodible implants of varying water solubility, size, and shape (Fig. 1a). By using PRINT particles with designed size and shape, a uniform distribution was achieved to further control release of the water soluble protein. Protein content, release, and activity were monitored in vitro with multiple techniques in PBS at 37°C. Safety, tolerability, and release were monitored in vivo.
Micrometer size PRINT protein particles were shown to possess high activity and uniform distributed throughout implants. Using monodisperse protein particles minimized variability in protein content between implants. Extended protein release was obtained for multiple implant formulations with strong dependence on implant composition (Fig. 1b). Increasing hydrophobic content decreased initial burst release and the rate of release over time, while not altering protein activity.
Bioerodible, hydrophobic materials offer the ability to control drug release of implants for intravitreal injection with sustained drug release. We have shown by utilizing the PRINT technology, protein content and distribution within such implants can be tightly controlled. This combination of bioerodible implants with uniformly distributed protein particles offers the possibility of extended release.
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