Glutathione PEGylated liposomes: pharmacokinetics and delivery of cargo across the blood-brain barrier in rats

J Drug Target. 2014 Jun;22(5):460-7. doi: 10.3109/1061186X.2014.888070. Epub 2014 Feb 14.


Partly due to poor blood-brain barrier drug penetration the treatment options for many brain diseases are limited. To safely enhance drug delivery to the brain, glutathione PEGylated liposomes (G-Technology®) were developed. In this study, in rats, we compared the pharmacokinetics and organ distribution of GSH-PEG liposomes using an autoquenched fluorescent tracer after intraperitoneal administration and intravenous administration. Although the appearance of liposomes in the circulation was much slower after intraperitoneal administration, comparable maximum levels of long circulating liposomes were found between 4 and 24 h after injection. Furthermore, 24 h after injection a similar tissue distribution was found. To investigate the effect of GSH coating on brain delivery in vitro uptake studies in rat brain endothelial cells (RBE4) and an in vivo brain microdialysis study in rats were used. Significantly more fluorescent tracer was found in RBE4 cell homogenates incubated with GSH-PEG liposomes compared to non-targeted PEG liposomes (1.8-fold, p < 0.001). In the microdialysis study 4-fold higher (p < 0.001) brain levels of fluorescent tracer were found after intravenous injection of GSH-PEG liposomes compared with PEG control liposomes. The results support further investigation into the versatility of GSH-PEG liposomes for enhanced drug delivery to the brain within a tolerable therapeutic window.

Keywords: Biodistribution; carboxyfluorescein; drug delivery; drug targeting; microdialysis; stability.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood-Brain Barrier / drug effects*
  • Blood-Brain Barrier / metabolism
  • Cell Line
  • Drug Carriers / administration & dosage
  • Drug Carriers / chemistry*
  • Drug Carriers / pharmacokinetics
  • Drug Stability
  • Endothelial Cells / drug effects
  • Endothelial Cells / metabolism
  • Fluoresceins
  • Fluorescent Dyes
  • Glutathione / administration & dosage
  • Glutathione / chemistry*
  • Glutathione / pharmacokinetics
  • Injections, Intravenous
  • Injections, Spinal
  • Liposomes
  • Microdialysis
  • Particle Size
  • Polyethylene Glycols / administration & dosage
  • Polyethylene Glycols / chemistry*
  • Polyethylene Glycols / pharmacokinetics
  • Rats
  • Rats, Wistar
  • Tissue Distribution


  • Drug Carriers
  • Fluoresceins
  • Fluorescent Dyes
  • Liposomes
  • 6-carboxyfluorescein
  • Polyethylene Glycols
  • Glutathione