Liposome‐Supported Peritoneal Dialysis for the Treatment of Hyperammonemia‐Associated Encephalopathy. (18th October 2016)

• Record Type: Journal Article
• Authors: Agostoni, Valentina; Lee, Soo Hyeon; Forster, Vincent; Kabbaj, Meriam; Bosoi, Cristina R.; Tremblay, Mélanie; Zadory, Matthias; Rose, Christopher F.; Leroux, Jean‐Christophe
• Is Part Of: Advanced functional materials. Volume 26:Number 46(2016)
• Page Start: 8382
• Page End: 8389
• Publication Date: 2016-10-18
• Subjects: detoxification -- hepatic encephalopathy -- hyperammonemia -- liposomes -- peritoneal dialysis; Materials -- Periodicals; Chemical vapor deposition -- Periodicals; 620.11
• DOI: 10.1002/adfm.201603519
• Languages: English
• ISSNs: 1616-301X

Abstract

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. Abstract : Liposome‐supported peritoneal dialysis appears as an effective, safe, and easy‐to‐implement ammonia detoxification therapy . Transmembrane pH‐gradient liposomes (acidic core) efficiently scavenge ammonia in the peritoneal space, outperforming conventional peritoneal dialysis, and significantly attenuating brain edema in cirrhotic rats. This study spans from the development of a manufacturing procedure suitable for clinical implementation to efficacy and safety assessment in appropriate animal models.