title: Sustained release of multiple growth factors from injectable polymeric system as a novel therapeutic approach towards angiogenesis.
abstract: OBJECTIVE
  The aim was to investigate that a bio-degradable alginate and poly lactide-co-glycolide (PLG) system capable of delivering growth factors sequentially would be superior to single growth factor delivery in promoting neovascularization and improving perfusion.
  
  
  METHODS
  Three groups of apoE null mice underwent unilateral hindlimb ischemia surgery and received ischemic limb intramuscular injections of alginate (Blank), alginate containing VEGF(165) (VEGF), or alginate containing VEGF(165) combined with PLG microspheres containing PDGF-BB (VEGF/PDGF). Vascularity in the ischemic hindlimb was assessed by morphologic and immunohistochemical end-points, while changes in blood flow were assessed by Laser Doppler Perfusion Index. Muscle VEGF and PDGF content was assessed at multiple time points.
  
  
  RESULTS
  In the VEGF/PDGF group, local tissue VEGF and PDGF levels peaked at week 2 and 4, respectively, with detectable PDGF levels at week 6. At week 6, mean vessel mean diameter was significantly greater in the VEGF/PDGF group compared to the VEGF or Blank groups with evidence of well-formed smooth muscle-lined arterioles.
  
  
  CONCLUSIONS
  Sequential delivery of VEGF and PDGF using an injectable, biodegradable platform resulted in stable and sustained improvements in perfusion. This sustained, control-released, injectable alginate polymer system is a promising approach for multiple growth factor delivery in clinical application.
authors: Division of Environmental Health Sciences, College of Public Health, The Ohio State University, Columbus, Ohio 43210-1252, USA. sun.224@osu.edu
authors: Qinghua
authors: Q
authors: Sun
authors: Eduardo A
authors: EA
authors: Silva
authors: Aixia
authors: A
authors: Wang
authors: James C
authors: JC
authors: Fritton
authors: David J
authors: DJ
authors: Mooney
authors: Mitchell B
authors: MB
authors: Schaffler
authors: Paul M
authors: PM
authors: Grossman
authors: Sanjay
authors: S
authors: Rajagopalan
mesh_terms: D000464:Alginates / Q000008:administration & dosage / Q000493:pharmacokinetics; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000818:Animals; D003692:Delayed-Action Preparations; D004337:Drug Carriers / Q000008:administration & dosage* / Q000493:pharmacokinetics; D016503:Drug Delivery Systems / Q000379:methods*; D020723:Glucuronic Acid / Q000008:administration & dosage / Q000493:pharmacokinetics; D006603:Hexuronic Acids / Q000008:administration & dosage / Q000493:pharmacokinetics; D006614:Hindlimb / Q000098:blood supply / Q000187:drug effects; D036341:Intercellular Signaling Peptides and Proteins / Q000008:administration & dosage* / Q000493:pharmacokinetics; D007511:Ischemia / Q000188:drug therapy / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D018919:Neovascularization, Physiologic / Q000187:drug effects* / Q000502:physiology; D011091:Polyesters / Q000008:administration & dosage / Q000493:pharmacokinetics; D011108:Polymers / Q000008:administration & dosage* / Q000493:pharmacokinetics; D011897:Random Allocation
chemical_list: D000464:Alginates; D020533:Angiogenesis Inhibitors; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D006603:Hexuronic Acids; D036341:Intercellular Signaling Peptides and Proteins; D011091:Polyesters; D011108:Polymers; C033616:poly(lactide); D020723:Glucuronic Acid