Osmotic Release of Bioactive VEGF from Biodegradable Elastomer Monoliths is the Same In Vivo As In Vitro

Abstract

The feasibility of generating an extended period of linear release of therapeutic proteins from photo-cross-linked, biodegradable elastomer monolithic devices in vitro has been previously demonstrated. The release is driven primarily by the osmotic pressure generated upon the dissolution of the encapsulated particles within the polymer. The osmotic pressure is provided by co-incorporation into the particle of trehalose as an osmotigen. Herein, we demonstrate that the release rate of a therapeutic protein, vascular endothelial growth factor (VEGF), by this osmotic pressure mechanism is the same in vivo as found in vitro. (125) I-VEGF was colyophilized with trehalose and serum albumin and distributed as particles throughout a photo-cross-linked elastomer composed of trimethylene carbonate, ε-caprolactone, and d,l-lactide. The release of VEGF from the device was monitored by measuring the decrease in radioactivity within the devices in vitro and within explanted devices that had been implanted subcutaneously in the dorsal area of Wistar rats. The released VEGF remained bioactive in vivo, inducing the formation of blood vessels that contained red blood cells. Furthermore, the released trehalose was well tolerated by the surrounding tissue.