Evaluation of recombinant human vascular endothelial growth factor VEGF121-loaded poly-l-lactide microparticles as a controlled release delivery system

Abstract

Vascular endothelial growth factor A (VEGF-A) is an important growth factor that plays a major role in angiogenesis. Withdifferent isoforms distributed in various tissues, the shortest isoform of VEGF-A is VEGF121, one of the physiologically functional variantsnext to VEGF165. It is well known that VEGF has a shorter half-life, and the stability of the protein must be considered in therapeuticaspects. Poly-l-lactide (PLA) microparticles can release the encapsulated protein in a sustained release mode. In this study, the VEGF121gene was cloned and expressed in a prokaryotic expression system (Escherichia coli). The recombinant VEGF121 was encapsulatedwith PLA microparticles and studied in vitro and ex ovo for the sustained release mechanism. The PLA-VEGF microparticles andthe recombinant VEGF121 were explored for their bioactivity in human umbilical vein endothelial cells (HUVEC). VEGF released invitro from PLA microparticles on days 1, 20, and 30 showed remarkable biological activity compared to PBS-loaded PLA microparticlessuch as the ability of the cells to proliferate, migrate, and form tubes similar to recombinant VEGF121. Besides, PLA-VEGF microparticlesand the recombinant VEGF121 were also tested for their proangiogenic action in embryonated eggs by chicken chorioallantoic membraneassay (CAM), and the effect was observed in both forms. This study suggests that PLA-loaded VEGF microparticles in a sustainablerelease format can be effectively used in proangiogenic therapy and reduce the adverse effects caused due to multiple dosages.