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


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.

DOI: 10.3109/1061186X.2014.888070

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@inproceedings{Rip2014GlutathionePL, title={Glutathione PEGylated liposomes: pharmacokinetics and delivery of cargo across the blood–brain barrier in rats}, author={Jaap Rip and Linda Chen and Robin Hartman and Angelique van den Heuvel and Arie Reijerkerk and Joan van Kregten and Burt van der Boom and Chantal Appeldoorn and Marco de Boer and David Maussang and Elizabeth C. M. de Lange and Pieter J. Gaillard}, booktitle={Journal of drug targeting}, year={2014} }