Functional benefits of PLGA particulates carrying VEGF and CoQ10 in an animal of myocardial ischemia

Int J Pharm. 2013 Oct 1;454(2):784-90. doi: 10.1016/j.ijpharm.2013.04.015. Epub 2013 Apr 29.

Abstract

Myocardial ischemia (MI) remains one of the leading causes of death worldwide. Angiogenic therapy with the vascular endothelial growth factor (VEGF) is a promising strategy to overcome hypoxia and its consequences. However, from the clinical data it is clear that fulfillment of the potential of VEGF warrants a better delivery strategy. On the other hand, the compelling evidences of the role of oxidative stress in diseases like MI encourage the use of antioxidant agents. Coenzyme Q10 (CoQ10) due to its role in the electron transport chain in the mitochondria seems to be a good candidate to manage MI but is associated with poor biopharmaceutical properties seeking better delivery approaches. The female Sprague Dawley rats were induced MI and were followed up with VEGF microparticles intramyocardially and CoQ10 nanoparticles orally or their combination with appropriate controls. Cardiac function was assessed by measuring ejection fraction before and after three months of therapy. Results demonstrate significant improvement in the ejection fraction after three months with both treatment forms individually; however the combination therapy failed to offer any synergism. In conclusion, VEGF microparticles and CoQ10 nanoparticles can be considered as promising strategies for managing MI.

Keywords: Angiogenesis; CVD; CoQ(10); DCM; DDS; DMSO; EF; HUVEC; MI; MP; Myocardial ischemia; NP; PEG; PLGA; PVA; Protein delivery; TROMS; Tissue engineering; VEGF; cardiovascular disease; coenzyme Q(10); dichloromethane; dimethylsulfoxide; drug delivery system; ejection fraction; human umbilical vein endothelial cell; microparticle; myocardial ischemia; nanoparticle; poly (ethylene glycol); poly (lactic-co-glycolic) acid; poly (vinyl alcohol); total recirculation one machine system; vascular endothelial growth factor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Proliferation / drug effects
  • Coronary Vessels / drug effects
  • Coronary Vessels / physiology
  • Disease Models, Animal
  • Female
  • Human Umbilical Vein Endothelial Cells / cytology
  • Human Umbilical Vein Endothelial Cells / drug effects
  • Humans
  • Lactic Acid / chemistry*
  • Myocardial Ischemia / drug therapy*
  • Myocardial Ischemia / pathology
  • Myocardial Ischemia / physiopathology
  • Myocardium / pathology
  • Nanoparticles / administration & dosage*
  • Nanoparticles / chemistry
  • Neovascularization, Physiologic / drug effects
  • Polyglycolic Acid / chemistry*
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Rats
  • Rats, Sprague-Dawley
  • Recombinant Proteins / administration & dosage*
  • Recombinant Proteins / chemistry
  • Stroke Volume / drug effects
  • Ubiquinone / administration & dosage
  • Ubiquinone / analogs & derivatives*
  • Ubiquinone / chemistry
  • Vascular Endothelial Growth Factor A / administration & dosage*
  • Vascular Endothelial Growth Factor A / chemistry
  • Vascular Endothelial Growth Factor A / genetics

Substances

  • Recombinant Proteins
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Ubiquinone
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polyglycolic Acid
  • Lactic Acid
  • coenzyme Q10