2-(2-Cholesteroxyethoxyl)ethyl-3′-S-glutathionylpropionate (COXP) for brain-targeting liposomes

Abstract

The blood-brain barrier (BBB) prevents a drug from reaching its therapeutic concentration in the brain resulting in a failure for the treatment of most brain diseases. Various approaches have been explored to develop brain-targeting agents that can help a drug or a drug delivery system to cross the BBB to reach the brain. A ligand or ligand analog of a BBB transporter or BBB receptor has been commonly employed to develop a brain targeting agent. We reported early 2-(2-cholesteroxyethoxyl)ethyl-3′-S-glutathionylpropionate (COXP) as a novel glutathione (GSH) transporter-mediated brain targeting agent based on the over-expression of GSH transporters at the BBB. COXP was obtained by connecting a molecule of GSH with a molecule of cholesterol via a two-ethylene glycol unit. COXP can self-assemble resulting in the formation of brain targeting micelles. Since cholesterol is one of the major components of liposomes, this work was designed to investigate if COXP could be used as a component of liposomes to prepare brain-targeting liposomes (COXP liposomes). Our results demonstrated that COXP liposomes effectively delivered DiR, a fluorescence tracking agent, to the brain of a mouse. The whole-body imaging of mice showed that the fluorescence intensity of DiR in the brain could reach 11 times higher for DiR delivered by COXP liposomes than that delivered by a cationic liposome which served as a control. The results show COXP's potential for developing novel brain-targeting liposomes.