Effect of Nanoparticle with VEGF in Mouse Ischemic Hindlimb Model

ABSTRACT

PURPOSE: Vascular endothelial growth factor (VEGF) is one of the factors regulating angiogenesis. For angiogenesis, the local concentration of VEGF has to be maintained. Because of its short half-life, VEGF has been conjugated with nanoparticles. Some nanoparticles, such as poly (lactic-co-glycolic acid (PLGA)) or polyethylenimine (PEI) are commonly used in this field, but have weak points such as faster release than expected and cell toxicity. We investigated the effect of core/shell nanoparticles including lecithin lipid cores in the ischemic hindlimb model. METHODS: Mice were anesthetized and a region of the common femoral artery and vein was ligated and excised. Hindlimb ischemic mice (n=28) were divided randomly into four groups: Control group (normal saline, n=7), mouse VEGF group (mVEGF, n=7), nanoparticle including mVEGF group (N-mVEGF, n=7), and nanoparticle/hydrogel mouse VEGF group (NH-mVEGF, n=7). The drug was injected postoperatively into the thigh muscle of the ischemic limb. Perfusion, capillary number and H&E stain were assessed 28 d after treatment. RESULTS: The capillary number increased in N-mVEGF and mVEGF group (P=0.026). Improvements of ischemic limb perfusion were inferior in N-mVEGF, NH-mVEGF groups (P=0.006) compared to other groups. Mice received N-mVEGF, NH-mVEGF treatment showed significant inflammation in the H&E staining. CONCLUSION: Sustained VEGF delivery via core/shell nanoparticle with lecithin core did not show improved perfusion rate despite an increase in capillary number. Furthermore, vacuolization and induction of inflammation requiring a different composition of nanoparticle should be tested.