Gene therapy of endometriosis introduced by polymeric micelles with glycolipid-like structure

Biomaterials. 2012 Jan;33(2):634-43. doi: 10.1016/j.biomaterials.2011.09.077. Epub 2011 Oct 13.

Abstract

To reduce the side effects and improve the lack of clinical treatment countermeasures in endometriosis chemotherapy, a polymeric micelle gene delivery system composed of lipid grafted chitosan micelles (CSO-SA) and the pigment epithelium derived factor (PEDF) was designed. Due to the cationic property, the glycolipid-like micelles could compact the PEDF to form complexes nanoparticles. The complexes nanoparticles with an N/P at 9.6 had 135.6 nm volume average hydrodynamic diameters with a narrow size distribution, and 6.4 ± 0.1 mV surface potential. PEDF can be distributed to endometriotic lesions in a rat model of peritoneal endometriosis mediated by CSO-SA via the intravenous injection. It showed that the CSO-SA/PEDF nanoparticles gene therapy caused decrease in the sizes of the endometriotic lesions and atrophy and degeneration of ectopic endometrium significantly. And it showed no toxicity to the reproductive organs under electron microscope observation. In addition, a reduction in microvessel density labeled by Von Willebrand factor was observed and no decrease in α-Smooth Muscle Actine-positive mature vessels. And the index of apoptotic was increased significantly in endometriotic lesions of CSO-SA/PEDF group. So, glycolipid-like structure micelles mediated PEDF gene delivery system could be used as an effective treatment approach for endometriosis disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Chitosan / chemistry
  • DNA / isolation & purification
  • Disease Models, Animal
  • Endometriosis / therapy*
  • Eye Proteins / chemistry
  • Eye Proteins / pharmacology*
  • Feasibility Studies
  • Female
  • Gene Transfer Techniques
  • Genetic Therapy*
  • Glycolipids / chemistry*
  • Micelles*
  • Microscopy, Electron, Transmission
  • Nerve Growth Factors / chemistry
  • Nerve Growth Factors / pharmacology*
  • Particle Size
  • Plasmids
  • Polymers / chemistry*
  • Rats
  • Rats, Sprague-Dawley
  • Serpins / chemistry
  • Serpins / pharmacology*

Substances

  • Eye Proteins
  • Glycolipids
  • Micelles
  • Nerve Growth Factors
  • Polymers
  • Serpins
  • pigment epithelium-derived factor
  • DNA
  • Chitosan