Sustained release of multiple growth factors from injectable polymeric system as a novel therapeutic approach towards angiogenesis

Pharm Res. 2010 Feb;27(2):264-71. doi: 10.1007/s11095-009-0014-0. Epub 2009 Dec 1.

Abstract

Purpose: 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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Alginates / administration & dosage
  • Alginates / pharmacokinetics
  • Angiogenesis Inhibitors / administration & dosage*
  • Angiogenesis Inhibitors / pharmacokinetics
  • Animals
  • Delayed-Action Preparations
  • Drug Carriers / administration & dosage*
  • Drug Carriers / pharmacokinetics
  • Drug Delivery Systems / methods*
  • Glucuronic Acid / administration & dosage
  • Glucuronic Acid / pharmacokinetics
  • Hexuronic Acids / administration & dosage
  • Hexuronic Acids / pharmacokinetics
  • Hindlimb / blood supply
  • Hindlimb / drug effects
  • Intercellular Signaling Peptides and Proteins / administration & dosage*
  • Intercellular Signaling Peptides and Proteins / pharmacokinetics
  • Ischemia / drug therapy
  • Ischemia / metabolism
  • Male
  • Mice
  • Mice, Knockout
  • Neovascularization, Physiologic / drug effects*
  • Neovascularization, Physiologic / physiology
  • Polyesters / administration & dosage
  • Polyesters / pharmacokinetics
  • Polymers / administration & dosage*
  • Polymers / pharmacokinetics
  • Random Allocation

Substances

  • Alginates
  • Angiogenesis Inhibitors
  • Delayed-Action Preparations
  • Drug Carriers
  • Hexuronic Acids
  • Intercellular Signaling Peptides and Proteins
  • Polyesters
  • Polymers
  • poly(lactide)
  • Glucuronic Acid