Concurrent delivery of dexamethasone and VEGF for localized inflammation control and angiogenesis

J Control Release. 2007 Jan 22;117(1):68-79. doi: 10.1016/j.jconrel.2006.10.013. Epub 2006 Oct 19.

Abstract

Localized elution of corticosteroids has been used in suppressing inflammation and fibrosis associated with implantation and continuous in vivo residence of bio-medical devices. However, these agents also inhibit endogenous growth factors preventing angiogenesis at the local tissue, interface thereby delaying the healing process and negatively impacting device performance. In this work, a combination of dexamethasone and vascular endothelial growth factor (VEGF) was investigated for concurrent localized delivery using PLGA microsphere/PVA hydrogel composites. Pharmacodynamic effects were evaluated by histopathological examination of subcutaneous tissue surrounding implanted composites using a rat model. The hydrogel composites were capable of simultaneously releasing VEGF and dexamethasone with approximately zero order kinetics. Composites were successful in controlling the implant/tissue interface by suppressing inflammation and fibrosis as well as facilitating neo-angiogenesis at a fraction of their typical oral or i.v. bolus doses. Implants containing VEGF showed a significantly higher number of mature blood vessels at the end of the 4 week study irrespective of the presence of dexamethasone. Thus, localized concurrent elution of VEGF and dexamethasone can overcome the anti-angiogenic effects of the corticosteroid and can be used to engineer inflammation-free and well-vascularized tissue in the vicinity of the implant. These PLGA microsphere/PVA hydrogel composites show promise as coatings for implantable bio-medical devices to improve biocompatibility and ensure in vivo performance.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Administration, Oral
  • Animals
  • Anti-Inflammatory Agents / administration & dosage*
  • Anti-Inflammatory Agents / pharmacology*
  • Dexamethasone / administration & dosage*
  • Dexamethasone / pharmacology*
  • Drug Carriers
  • Fibrosis
  • Hydrogels
  • Inflammation / pathology
  • Injections, Intravenous
  • Lactic Acid
  • Microspheres
  • Neovascularization, Physiologic / drug effects*
  • Polyglycolic Acid
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polymers
  • Polyvinyls
  • Rats
  • Serum Albumin
  • Vascular Endothelial Growth Factor A / administration & dosage*
  • Vascular Endothelial Growth Factor A / pharmacology*

Substances

  • Anti-Inflammatory Agents
  • Drug Carriers
  • Hydrogels
  • Polymers
  • Polyvinyls
  • Serum Albumin
  • Vascular Endothelial Growth Factor A
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polyglycolic Acid
  • Lactic Acid
  • Dexamethasone