title: Liposome-supported peritoneal dialysis for detoxification of drugs and endogenous metabolites.
abstract: Peritoneal dialysis confers therapeutic advantages in patients with renal insufficiency and has proven beneficial in other indications, such as removal of excess metabolites or overdosed drugs. However, it is used in only about 10% of the dialyzed population worldwide, partly owing to the lower clearance rate compared with hemodialysis. We have developed a dialysis medium based on liposomes with a transmembrane pH gradient (basic or acidic aqueous core) that could improve the efficacy of peritoneal dialysis, specifically for the removal of excess metabolites or overdosed drugs. These scavenging vesicles are able to extract ionizable drugs and toxic metabolites into the peritoneal space and can be easily withdrawn from the body at the end of dialysis. This approach was used to successfully remove ammonia from rats with a greater extraction efficiency than traditional peritoneal dialysis, and may therefore prove useful in the treatment of severe hyperammonemia. Liposomal dialysis was also used to concentrate exogenous compounds in the rat peritoneal cavity, allowing for sequestration of several drugs that are frequently involved in overdose in people. In particular, liposomal dialysis counteracted the hypotensive action of the cardiovascular drug verapamil more efficiently than did control dialysis in a rat model of drug overdose. These findings highlight the versatility and advantage of this liposome-based approach for emergency dialysis.
authors.affiliation: Institute of Pharmaceutical Sciences, Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology, ETH Zurich, Vladimir Prelog Weg 1-5/10, 8093 Zurich, Switzerland.
authors.forename: Vincent
authors.initials: V
authors.lastname: Forster
authors.affiliation: Institute of Pharmaceutical Sciences, Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology, ETH Zurich, Vladimir Prelog Weg 1-5/10, 8093 Zurich, Switzerland.
authors.forename: Rea Deborah
authors.initials: RD
authors.lastname: Signorell
authors.affiliation: Institute of Pharmaceutical Sciences, Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology, ETH Zurich, Vladimir Prelog Weg 1-5/10, 8093 Zurich, Switzerland.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Roveri
authors.affiliation: Institute of Pharmaceutical Sciences, Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology, ETH Zurich, Vladimir Prelog Weg 1-5/10, 8093 Zurich, Switzerland. jleroux@ethz.ch.
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Leroux
mesh_terms: D000143:Acids / Q000378:metabolism; D000641:Ammonia / Q000378:metabolism; D000818:Animals; D062787:Drug Overdose / Q000378:metabolism; D006439:Hemodynamics; D008658:Inactivation, Metabolic; D008081:Liposomes / Q000737:chemistry*; D008297:Male; D055442:Metabolome; D010530:Peritoneal Dialysis / Q000379:methods*; D004364:Pharmaceutical Preparations / Q000737:chemistry / Q000378:metabolism*; D017207:Rats, Sprague-Dawley
chemical_list: D000143:Acids; D008081:Liposomes; D004364:Pharmaceutical Preparations; D000641:Ammonia