Drug Displacement Strategy for Treatment of Acute Liver Injury with Cyclodextrin-Liposome Nanoassembly

Biofunctional supramolecular assemblies that combine macrocyclic receptors and amphiphiles are potent drug delivery systems, but optimization and implementation challenges remain. We herein describe a cooperative drug displacement strategy exemplified by the use of cyclodextrin-liposome supramolecular nanoassemblies as a therapy for acute liver injury. The hepatoprotective drug silibinin was solubilized in phosphotyramine-modified β-cyclodextrin, and subsequent encapsulation of the silibinin-cyclodextrin complex in phosphatidylcholine liposomes gave uniformly sized and stable nanoassemblies that accumulated preferentially in the liver of mice. Enzymatic cleavage of the phosphate ester of the β-cyclodextrin resulted in rapid release of the encapsulated silibinin. Significantly, silibinin could be readily displaced by cytotoxic bile acids, thus leading to the removal of excess bile acids from the bodies of mice and the recovery of liver function. Our results demonstrate that cyclodextrin-based nanoassemblies with a dual role of solubilizing a drug and removing toxins constitute a promising therapy for hepatic injury.