Brain disease treatment has been hampered by a highly selective semipermeable barrier called the blood-brain barrier (BBB). The BBB protects the brain by restricting the entry of endogenous and exogenous toxins. Most therapeutics are prevented from passing through the BBB resulting in a treatment failure of brain diseases. <br/><br/>Various transporters and receptors are located in the BBB helping transport needed substances to the brain such as nutrients, amino acids, and peptides or interacting with a ligand to play a cellular function. Ligands for some of these transporters or receptors have been used as brain-targeting agents to improve drug delivery to the brain. Glutathione (GSH) is an endogenous tripeptide. It enters the brain by a sodium-dependent GSH transporter that is highly distributed over the BBB. GSH has been found to be a good brain-targeting ligand. <br/><br/>In this poster, we would like to present the design, synthesis, and characterization of GUNW-3 as a brain targeting agent. GUNW-3 was synthesized in 4 steps in an overall 60% yield. The brain-targeting ability of GUNW-3 was demonstrated by its ability to deliver effectively liposomes and micelles to the brain. The preparation and characterization of GUNW-3 liposomes and GUNW-3 micelles will be presented. Our preliminary studies with mice through in vivo bioimaging technique using near-infrared dye DiR revealed that the GUNW-3 liposomes improved the brain delivery of liposomes by 21 folds. More impressively, GUNW-3 micelles demonstrated an even better and lasting brain-targeting effect than GUNW-3 liposomes with a minimal distribution in the liver. GUNW-3 is a promising brain-targeting agent.

Design, synthesis, and evaluation of GUNW-3 as a brain-targeting agent

2019 Fall National Meeting

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