Drug overdose treatment using long circulating liposomes

COLL 501

Brett A Howell, bahowel2@ufl.edu and Anuj Chauhan, chauhan@che.ufl.edu. Department of Chemical Engineering, University of Florida, PO Box 116005, Gainesville, FL 32611-6005
Tricyclic antidepressants such as amitriptyline are commonly involved in drug overdose cases. We have focused on developing liposomal systems that can be injected intravenously to treat the overdoses. We will report binding isotherms for the drug with plasma proteins and liposomes. Also the binding isotherms will be reported for liposomes in human serum, and effects of lipid type, charge, lipid loading, liposome size, polymer (PEG) inclusion, and storage will be described. The 95:5 DOPG:DPPE-mPEG-2000 liposomes loaded at 1.44 mg lipid/mL are able to reduce the free drug concentration in serum by about 90% over drug concentration range of 1 µM to 20 µM. These are equally effective at binding nortriptyline, which is the main metabolite of amitriptyline. These systems are highly biocompatible, and have reasonably long circulation lives and so these are expected to successfully treat amitriptyline overdoses, and possibly overdose from other drugs.