Encapsulation of VEGF₁₆₅ into magnetic PLGA nanocapsules for potential local delivery and bioactivity in human brain endothelial cells

Angiogenesis is an important repairing mechanism in response to ischemia. The administration of proangiogenic proteins is an attractive therapeutic strategy to enhance angiogenesis after an ischemic event. Their labile structures and short circulation times in vivo are the main obstacles that reduce the bioactivity and dosage of such proteins at the target site. We report on poly(D,L-lactic-co-glycolic acid)(PLGA) nanocapsules (diameter < 200 nm) containing bioactive vascular endothelial growth factor-165 (VEGF165) in the inner core and superparamagnetic iron oxide nanoparticles (SPIONs) embedded in the polymeric shell. The system showed good encapsulation efficiencies for both VEGF165 and SPIONs and a sustained protein release over 14 days. In vitro studies confirmed protein bioactivity in the form of significantly increased proliferation in human microvascular brain endothelial cell cultures once the protein was released. Through magnetic resonance imaging (MRI) measurements we demonstrated excellent T2 contrast image properties with r2 values as high as 213 mM-1 s-1. In addition, magnetic VEGF165-loaded PLGA nanocapsules could be displaced and accumulated under an external magnetic field for guiding and retention purposes. We therefore suggest that using VEGF165-loaded magnetic PLGA nanocapsules may become a new targeted protein-delivery strategy in the development of future pro-angiogenic treatments, as for instance those directed to neurorepair after an ischemic event