Sustained Proangiogenic Activity of Vascular Endothelial Growth Factor Following Encapsulation in Nanoparticles

The success of proangiogenic growth factors for therapeutic angiogenesis in the treatment of ischemic diseases is currently hindered, in part, due to the lack of an optimal drug delivery system that can provide sustained therapeutic doses of these agents selectively in the diseased tissue. The objective of this study was to investigate the efficacy of sustained release biodegradable nanoparticles, formulated with poly (D,L-lactide-co-glycolide) polymer, for the delivery of vascular endothelial growth factor protein (VEGF), a potent proangiogenic agent. The hypothesis was that nanoparticles would protect the growth factor from degradation and release it slowly thereby sustaining and enhancing its proangiogenic effect. Nanoparticles encapsulating VEGF, which were formulated using a water-in-oil-in-water solvent evaporation technique, demonstrated sustained release of the growth factor in bioactive form. Further, the growth factor encapsulated in nanoparticles demonstrated greater and more sustained effect than when used as a solution on endothelial cell proliferation, migration, and morphogenesis, the key elements of angiogenesis. The greater efficacy of the growth factor encapsulated in nanoparticles was due to the ability of nanoparticles to maintain the growth factor level in culture for a sustained period of time. The data thus suggest that nanoparticles can be used as an effective delivery system for growth factors to induce therapeutic angiogenesis.