title: Co-delivery of vascular endothelial growth factor and angiopoietin-1 using injectable microsphere/hydrogel hybrid systems for therapeutic angiogenesis.
abstract: OBJECTIVE
  We hypothesized that combined delivery of vascular endothelial growth factor (VEGF) and angiopoietin-1 (Ang-1) using microsphere/hydrogel hybrid systems could enhance mature vessel formation compared with administration of each factor alone.
  
  
  METHODS
  Hybrid delivery systems composed of alginate hydrogels and poly(D,L-lactic-co-glycolic acid) (PLGA) microspheres containing angiogenic factors were prepared. The release behavior of angiogenic factors from hybrid systems was monitored in vitro. The hybrid systems were injected into an ischemic rodent model, and blood vessel formation at the ischemic site was evaluated.
  
  
  RESULTS
  The sustained release over 4 weeks of both VEGF and Ang-1 from hybrid systems was achieved in vitro. Co-delivery of VEGF and Ang-1 was advantageous to retain muscle tissues and significantly induced vessel enlargement at the ischemic site, compared to mice treated with either VEGF or Ang-1 alone.
  
  
  CONCLUSIONS
  Sustained and combined delivery of VEGF and Ang-1 significantly enhances vessel enlargement at the ischemic site, compared with sustained delivery of either factor alone. Microsphere/hydrogel hybrid systems may be a promising vehicle for delivery of multiple drugs for many therapeutic applications.
authors.affiliation: Department of Bioengineering, Hanyang University, Seoul 133-791, Republic of Korea.
authors.forename: Seung-Hwa
authors.initials: SH
authors.lastname: Shin
authors.forename: Jangwook
authors.initials: J
authors.lastname: Lee
authors.forename: Dong-Gyun
authors.initials: DG
authors.lastname: Ahn
authors.forename: Kuen Yong
authors.initials: KY
authors.lastname: Lee
mesh_terms: D000464:Alginates / Q000737:chemistry; D042683:Angiopoietin-1 / Q000008:administration & dosage*; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D003692:Delayed-Action Preparations / Q000737:chemistry*; D005260:Female; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D006614:Hindlimb / Q000098:blood supply / Q000187:drug effects; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry*; D019344:Lactic Acid / Q000737:chemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008863:Microspheres; D018919:Neovascularization, Physiologic / Q000187:drug effects; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D042461:Vascular Endothelial Growth Factor A / Q000008:administration & dosage*
chemical_list: D000464:Alginates; D042683:Angiopoietin-1; D003692:Delayed-Action Preparations; D006603:Hexuronic Acids; D042461:Vascular Endothelial Growth Factor A; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D011100:Polyglycolic Acid; D019344:Lactic Acid; D020723:Glucuronic Acid