A novel PEG-haloperidol conjugate with a non-degradable linker shows the feasibility of using polymer-drug conjugates in a non-prodrug fashion

Abstract

A PEG-haloperidol conjugate containing a non-biodegradable linker was synthesised. Incubation with rat plasma demonstrated excellent linker stability, and competition radioligand binding assays demonstrated retained binding to the D2-receptor. In silico studies predicted that the conjugate will not cross the blood-brain barrier (BBB), thus potentially restricting haloperidol action to one side of the BBB.