Liposome‐Supported Peritoneal Dialysis for the Treatment of Hyperammonemia‐Associated Encephalopathy

Abstract

Hyperammonemia can lead to cerebral dysfunction, encephalopathy, coma, and death if not treated adequately. The poor prognosis associated with this condition reflects the unmet medical need for effective ammonia‐lowering treatments. Here, the translational potential of liposome‐supported peritoneal dialysis (LSPD), a recently‐developed detoxification strategy for the removal of small ionizable molecules like ammonia, is described. Dialysis fluids supplemented with micrometer‐sized, transmembrane pH‐gradient liposomes are prepared via an innovative, osmotic shock‐based method overcoming sterilization and long‐term stability issues. LSPD is able to sequester ammonia in healthy rats in relation to the injected dose, buffering capacity of the liposomal core, and membrane composition. In a rat model of cirrhosis, LSPD outperforms conventional peritoneal dialysis in lowering plasmatic ammonia levels and attenuating brain edema. LSPD does not trigger any hypersensitive reaction in pigs, a side effect commonly observed upon the injection of colloids in this animal model and in humans. These findings support the development of LSPD for the treatment of hyperammonemia‐induced encephalopathy.