[Polymeric nanoparticles with therapeutic gene for gene therapy: I. Preparation and in vivo gene transfer study]

Sheng Wu Yi Xue Gong Cheng Xue Za Zhi. 2005 Jun;22(3):438-42.
[Article in Chinese]

Abstract

VEGF nanoparticle (VEGF-NP) was prepared by a multi-emulsification technique using a biodegradable poly-dl-lactic-co-glycolic (PLGA) as matrix material. The nanoparticles were characterized for size, VEGF loading capacity, and in vitro release. VEGF-NP and naked VEGF plasmid were intramuscularly injected into the ischemia site of the rabbit chronic hindlimb ischemia model and the efficiency of VEGF-NP as gene delivery carrier for gene therapy in animal model was evaluated. Gene therapuetic effect was assessed evaluated by RT-PCR, immunohistochemistry and angiography assay. The average size of VEGF-NP was around 300 nm. The encapsulation efficiency of VEGF was above 96%. Loading amount of VEGF in the nanoparticles was about 4%. In vitro, nanoparticles maintained sustained-release of VEGF for two weeks. Two weeks post gene injection the capillary density in VEGF-NP group (81.22 per mm2) was significantly higher than that in control group (29.54 mm2). RT-PCR results showed greatly higher VEGF expression in VEGF-NP group (31.79au * mm) than that in naked VEGF group (9.15 au * mm). As a carrier system for gene therapy in animal model, VEGF-NP is much better than naked DNA plasmid. The results demonstrate great possibility of using NP carrier in human gene therapy.

MeSH terms

  • Animals
  • Disease Models, Animal
  • Gene Transfer Techniques
  • Genetic Therapy*
  • Genetic Vectors / chemistry
  • Lactic Acid / chemistry*
  • Nanoparticles / chemistry*
  • Plasmids
  • Polyglycolic Acid / chemistry*
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Rabbits
  • Vascular Endothelial Growth Factor A / genetics*

Substances

  • Vascular Endothelial Growth Factor A
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polyglycolic Acid
  • Lactic Acid