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

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.