%0 Journal Article %J Pharm Res %D 2005 %T Sustained vascular endothelial growth factor delivery enhances angiogenesis and perfusion in ischemic hind limb %A Sun, Qinghua %A Chen, Ruth R %A Shen, Yuechun %A Mooney, David J %A Rajagopalan, Sanjay %A Grossman, P Michael %K Actins %K Animals %K Antigens, CD31 %K Biocompatible Materials %K Capillaries %K Disease Models, Animal %K Drug Carriers %K Hindlimb %K Humans %K Ischemia %K Lactic Acid %K Laser-Doppler Flowmetry %K Male %K Mice %K Mice, Inbred C57BL %K Muscle, Skeletal %K Neovascularization, Physiologic %K Perfusion %K Polyglycolic Acid %K Polymers %K Vascular Endothelial Growth Factor A %X PURPOSE: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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. %B Pharm Res %V 22 %P 1110-6 %8 2005 Jul %G eng %N 7 %1 http://www.ncbi.nlm.nih.gov/pubmed/16028011?dopt=Abstract %R 10.1007/s11095-005-5644-2