Pharmaceutical Research

, Volume 22, Issue 7, pp 1110–1116

Sustained Vascular Endothelial Growth Factor Delivery Enhances Angiogenesis and Perfusion in Ischemic Hind Limb

Authors

  • Qinghua Sun
    • Division of Cardiovascular Medicine, Department of Internal MedicineUniversity of Michigan Hospitals and Health System
  • Ruth R. Chen
    • Department of Biologic and Materials SciencesUniversity of Michigan
  • Yuechun Shen
    • Division of Cardiovascular Medicine, Department of Internal MedicineUniversity of Michigan Hospitals and Health System
  • David J. Mooney
    • Department of Biologic and Materials SciencesUniversity of Michigan
  • Sanjay Rajagopalan
    • Division of Cardiovascular Medicine, Department of Internal MedicineUniversity of Michigan Hospitals and Health System
    • Division of Cardiovascular Medicine, Department of Internal MedicineUniversity of Michigan Hospitals and Health System
Research Paper

DOI: 10.1007/s11095-005-5644-2

Cite this article as:
Sun, Q., Chen, R.R., Shen, Y. et al. Pharm Res (2005) 22: 1110. doi:10.1007/s11095-005-5644-2

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 (∅-Implant), unloaded scaffold implantation (Empty-PLG), or implantation of scaffolds incorporating 3 μg of VEGF165 (PLG-VEGF). Endpoints included laser Doppler perfusion imaging (LDPI, ischemic/nonischemic limb, %), local vessel counts, immunohistochemistry for CD31, and α-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 α-smooth muscle actin compared to the Empty-PLG or ∅-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.

Key Words

angiogenesisischemiapolymervascular endothelial growth factor

Abbreviations

Empty-PLG

PLG polymer not loaded with growth factor

∅-Implant

hind limb surgery performed with no PLG polymer implanted

PAD

peripheral arterial disease

PLG

poly(lactide-co-glycolide)

PLG-VEGF

PLG polymer loaded with 3 μg of VEGF165

SMA

smooth muscle actin

VEGF

vascular endothelial growth factor

Copyright information

© Springer Science + Business Media, Inc. 2005