Sustained vascular endothelial growth factor delivery enhances angiogenesis and perfusion in ischemic hind limb

• Published in: Pharmaceutical research Vol. 22; no. 7; pp. 1110 - 1116
• Main Authors: Sun, Qinghua, Chen, Ruth R, Shen, Yuechun, Mooney, David J, Rajagopalan, Sanjay, Grossman, P Michael
• Format: Journal Article
• Language: English
• Published: United States Springer Nature B.V 01.07.2005
• Subjects: Actins - metabolism; Angiogenesis; Animals; Biocompatible Materials - administration & dosage; Capillaries - growth & development; Disease Models, Animal; Drug Carriers; Drug delivery systems; Hindlimb - blood supply; Hindlimb - physiopathology; Humans; Ischemia; Ischemia - drug therapy; Ischemia - physiopathology; Laboratory animals; Lactic Acid - administration & dosage; Laser-Doppler Flowmetry; Male; Mice; Mice, Inbred C57BL; Muscle, Skeletal - blood supply; Muscle, Skeletal - physiopathology; Neovascularization, Physiologic - drug effects; Perfusion; Platelet Endothelial Cell Adhesion Molecule-1 - metabolism; Polyglycolic Acid - administration & dosage; Polymers; Polymers - administration & dosage; Smooth muscle; Surgery; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A - administration & dosage; Veins & arteries; Ann Arbor Michigan; United States > US; Michigan
• ISSN: 0724-8741; 1573-904X
• DOI: 10.1007/s11095-005-5644-2

We hypothesized that sustained delivery of vascular endothelial growth factor (VEGF) using a polymer [85:15 poly(lactide-co-glycolide) (PLG)] would enhance angiogenesis and improve perfusion of ischemic tissue. C57BL/6J mice (n = 20/group) underwent unilateral hind limb ischemia surgery and were randomized to groups of no scaffold implantation (0-Implant), unloaded scaffold implantation (Empty-PLG), or implantation of scaffolds incorporating 3 microg of VEGF165 (PLG-VEGF). Endpoints included laser Doppler perfusion imaging (LDPI, ischemic/nonischemic limb, %), local vessel counts, immunohistochemistry for CD31, and alpha-smooth muscle actin. In vitro release kinetics of VEGF from PLG was also measured. PLG-VEGF resulted in improved lower extremity perfusion vs. controls as measured by LDPI% at 7, 14, 21, and 28 days (p < 0.05). PLG-VEGF was associated with significantly greater percentage of vessels staining for CD31 and alpha-smooth muscle actin compared to the Empty-PLG or 0-Implant (p < 0.05 for both). The PLG-VEGF scaffolds resulted in sustained VEGF delivery, improved tissue perfusion, greater capillary density, and more mature vasculature compared to the controls. The sustained-release PLG polymer vehicle is a promising delivery system for therapeutic neovascularization applications.