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- Title
Liposome-Supported Peritoneal Dialysis for the Treatment of Hyperammonemia-Associated Encephalopathy.
- Authors
Agostoni, Valentina; Lee, Soo Hyeon; Forster, Vincent; Kabbaj, Meriam; Bosoi, Cristina R.; Tremblay, Mélanie; Zadory, Matthias; Rose, Christopher F.; Leroux, Jean‐Christophe
- 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.
- Subjects
PERITONEAL dialysis; LIPOSOMES; HYPERAMMONEMIA; HEPATIC encephalopathy; AMMONIA; COMA; DEATH; LABORATORY rats; THERAPEUTICS
- Publication
Advanced Functional Materials, 2016, Vol 26, Issue 46, p8382
- ISSN
1616-301X
- Publication type
Article
- DOI
10.1002/adfm.201603519