title: Glutathione PEGylated liposomes: pharmacokinetics and delivery of cargo across the blood-brain barrier in rats.
abstract: 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.
authors: to-BBB technologies BV , Leiden , The Netherlands and.
authors: Jaap
authors: J
authors: Rip
authors: Linda
authors: L
authors: Chen
authors: Robin
authors: R
authors: Hartman
authors: Angelique
authors: A
authors: van den Heuvel
authors: Arie
authors: A
authors: Reijerkerk
authors: Joan
authors: J
authors: van Kregten
authors: Burt
authors: B
authors: van der Boom
authors: Chantal
authors: C
authors: Appeldoorn
authors: Marco
authors: M
authors: de Boer
authors: David
authors: D
authors: Maussang
authors: Elizabeth C M
authors: EC
authors: de Lange
authors: Pieter J
authors: PJ
authors: Gaillard
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000378:metabolism; D002460:Cell Line; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D004355:Drug Stability; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D005452:Fluoresceins; D005456:Fluorescent Dyes; D005978:Glutathione / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D007275:Injections, Intravenous; D007278:Injections, Spinal; D008081:Liposomes; D017551:Microdialysis; D010316:Particle Size; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution
chemical_list: D004337:Drug Carriers; D005452:Fluoresceins; D005456:Fluorescent Dyes; D008081:Liposomes; C024098:6-carboxyfluorescein; D011092:Polyethylene Glycols; D005978:Glutathione
keywords: Biodistribution; carboxyfluorescein; drug delivery; drug targeting; microdialysis; stability