G-Technology

The G-Technology® offers the safest possibility to enhance the delivery of drugs that do not readily reach the brain within a favorable therapeutic window. Realistically, this technology is not a magic bullet that delivers drug exclusively to the brain; however, the ability of the PEGylated liposomes to encapsulate hydrophilic as well as lipophilic compounds, ranging from small molecules to biologics, gives a versatility that is an important benefit additional to the safety of this brain drug delivery platform.

Features of the G-Technology

  • safest technology to date, as all components are already used in clinical practice. The first product based on the G-Technology has successfully completed preclinical development and has now entered the clinical development phase
  • a liposomal drug delivery system
    • able to carry a range of compounds, from small molecules to biologics, from hydrophilic to lipophilic and even low soluble drugs
    • protects the body from side effects caused by peak concentrations of the drug
    • addition of PEG shields the liposome to ensure a long circulation time in the blood stream
  • glutathione (often abbreviated as GSH) is conjugated to the tips of PEG for enhanced drug delivery to the brain
    • glutathione is an endogenous anti-oxidant tripeptide involved in cellular detoxifying mechanisms, and is specifically and actively taken up by specialized transporters at the blood-brain barrier
    • glutathione is used as supportive therapy in cancer, HIV and Parkinson's Disease (in high intravenous doses) and as a food supplement. It has FDA GRAS (generally regarded as safe) status
    • the G-Technology uses GSH levels well below the endogenous GSH levels and the GSH transporter capacity, thereby ruling out potential interference with the endogenous function of GSH in the brain
    • enhanced brain delivery through endogenous GSH transporters keep the neuroprotective blood-brain barrier function completely intact, which is essential for brain functioning; blood-brain barrier opening or disruption is simply not clinically acceptable for the delicate (diseased) brain

The G-Technology in practice

to-BBB, together with its collaborators, has investigated the safety, efficacy and mechanism of the G-Technology.

  • the G-Technology loaded with peptides and small molecules exerted a superior effect in models for pain, brain tumorsviral encephalitis, and neuroinflammation when compared to non-targeted liposomes and free drugs
  • a technologic and mechanistic validation assay using microdialysis has shown that the delivery of free drug to the extracellular fluid of the brain was specifically enhanced by the G-Technology; increasing the amount of glutathione on the outside of the liposomes resulted up to a 5 times higher free drug concentration compared to non-targeted liposomes
  • cell-based assays have further demonstrated a glutathione specific and active endocytotic uptake mechanism for the G-Technology
  • on another note, independent research groups have employed glutathione-conjugation directly to drugs or to nanoparticles and reported similar enhanced uptake data

Origin of the G-Technology

Based on literature findings and on previous unpublished validation results from the drug delivery department of Dr. Maggie Lu at the Industrial Technology Research Institute (ITRI) in Hsin-Chu, Taiwan R.O.C., ITRI was the first in 2005 to file patents describing glutathione-mediated drug delivery to the brain. In 2008, to-BBB technologies BV obtained the exclusive worldwide rights to commercialize these patents for the targeted delivery of drugs to the brain.

Literature on glutathione transporters at the blood-brain barrier:

Kannan, 2000.; Brain Res

Kannan, 1990; J Clin Invest

Zlokovic, 1994; Biochem Biophys Res Commun