Local and sustained vascular endothelial growth factor delivery for angiogenesis using an injectable system.
OBJECTIVE
We hypothesize that a microsphere/hydrogel combination system could be useful for the local and sustained delivery of recombinant human vascular endothelial growth factor (rhVEGF) to enhance angiogenesis in vivo.


METHODS
Poly(D,L-lactide-co-glycolide) (PLGA) microspheres containing rhVEGF were loaded into alginate gels by ionic cross-linking. The rhVEGF release from the system was monitored and bioactivity was tested in vitro. The combination system was subcutaneously injected into mice using a syringe, and new blood vessel formation was evaluated.


RESULTS
Sustained rhVEGF release from the combination system was observed for 3 weeks, and the released rhVEGF remained bioactive. Endothelial cell proliferation was significantly enhanced when cells were cultured with the rhVEGF-releasing combination system in vitro. When the combination system was implanted, the granulation tissue layer was thicker with more newly formed blood vessels than that with a single dose VEGF injection.


CONCLUSIONS
The rhVEGF release was controlled by varying relative portions of microspheres and hydrogels in combination delivery systems, which efficiently promoted new blood vessel formation in vivo. This combination system could be a promising delivery vehicle for therapeutic angiogenesis.
Lee
Jangwook
J
Department of Bioengineering, Hanyang University, Seoul 133-791, Republic of Korea.
Lee
Kuen Yong
KY
D000464:Alginates / Q000737:chemistry*; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003432:Cross-Linking Reagents; D016503:Drug Delivery Systems / Q000379:methods*; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D006801:Humans; D020100:Hydrogels / Q000737:chemistry*; D055104:Infusions, Subcutaneous; D019344:Lactic Acid; D051379:Mice; D008863:Microspheres; D018919:Neovascularization, Physiologic / Q000187:drug effects; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000235:genetics / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A / Q000008:administration & dosage* / Q000235:genetics / Q000494:pharmacology*
D000464:Alginates; D003432:Cross-Linking Reagents; D006603:Hexuronic Acids; D020100:Hydrogels; D011994:Recombinant Proteins; D042461:Vascular Endothelial Growth Factor A; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D020723:Glucuronic Acid