Abstract 19225: Sustained Release of VEGF via PLGA Nanoparticles Improves Vascularization in vitro and in vivo
Introduction: Vascular endothelial growth factor (VEGF) has a leading role in the angiogenic process and is a promising agent to promote revascularization in the infarcted heart. Several clinical trials with low doses of VEGF failed due to the shorter half-life of VEGF when administered directly to the tissue. However, clinical trials with high VEGF doses showed improvements in cardiac vascularization but leading to severe side effects such as hypotension, retinopathy, or progression of malignant tumors. We hypothesized that encapsulating VEGF in PLGA nanoparticles will preserve the functional properties and improve the half-life of VEGF. Additionally, sustained release of VEGF from the nanoparticles would maintain intracellular VEGF levels avoiding excessive administrations and thus eliminating VEGF-induced side effects.
Methods: VEGF encapsulated PLGA nanoparticles were prepared by a double emulsion (water/oil/water phase) method. Nanoparticle characters such as size and VEGF release profile were studied using NanoSight and human VEGF ELISA kit, respectively. Effect of VEGF on HUVEC cell proliferation was analyzed by MTS.
Results: VEGF nanoparticles of 115 nm average size, a preferred nano-range for drug delivery studies, were successfully prepared. Encapsulation efficiency, another major character that defines the quality of nanoparticles was estimated to be 53.5% corresponding to a loading efficiency of 107.1 ng VEGF per mg of nanoparticles. VEGF in vitro time kinetics showed that 21% of VEGF was released in the first 6 hours increasing up to a 29% of release at 72 hours. Additionally, VEGF nanoparticles increased proliferation of HUVEC cells by 6.7 folds compared to non-treated cell group. At this lower dose, free VEGF did not induce a significant increase in cell proliferation indicating that sustained presence of VEGF is an essential factor for cell proliferation. The in vivo results will be discussed at the meeting.
Conclusions: Our data clearly shows that encapsulating VEGF in PLGA nanoparticles has a potential in enhancing the physiological and therapeutic functions of VEGF. Thus, VEGF-PLGA nanoparticles can be considered as a promising drug delivery system to promote revascularization in the damaged myocardium of cardiac patients.
Author Disclosures: Y. Oduk: None. R. Kannappan: None. W. Zhu: None. J. Zhang: None.
- © 2016 by American Heart Association, Inc.