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vesicles are able to extract ionizable drugs and toxic metabolites into the peritoneal space and can be easily withdrawn from the body at the end of dialysis.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.

Nano-antidotes for drug overdose and poisoning

“…The liposomal formulation was more potent than the commercially available ILEs, with a recovery time more than 30% faster. Intraperitoneal injection of the liposomes allowed efficient sequestration of several drugs (propranolol, amitriptyline, haloperidol, phenobarbital, and verapamil) in the peritoneal cavity prior to removal; in the case of verapamil, peritoneal dialysis with liposomes resulted in a dramatic shortening of recovery time compared with standard peritoneal dialysis (20).…”

“…This response could be problematic in weakened, intoxicated patients, especially at the relatively high doses that are often injected in rescue protocols. One possible solution could be the administration of the antidotal particles intraperitoneally (20), to minimize systemic exposure to the drug scavengers. Another approach, although more invasive, could consist of purifying the blood extracorporally by passing it through a mesh containing the immobilized scavenging nanoparticles (64).…”

Developments in extracorporeal therapy for the poisoned patient

“…Their results showed clearance of ammonia approaching that of hemodialysis. They also successfully removed verapamil and were able to concentrate amitriptyline, propranolol, haloperidol and phenobarbital in the rat peritoneal cavity [65].…”

Increasing the removal of protein‐bound uremic toxins by liposome‐supported hemodialysis

“…The ability of liposomes to encapsulate a wide variety of bioactive agents has led to substantial interest in utilizing liposomes as nanocarriers for the detection and treatment of a variety of diseases (15). Recently, Froster et al (17) developed a dialysis medium based on liposomes with a transmembrane pH gradient (basic or acidic aqueous core) and showed that liposome-supported peritoneal dialysis was able to improve the extraction of endogenous ammonia and ionizable drugs in rat models. For example, Wratten et al (16) reported that adding liposomes containing a-tocopherol (vitamin E) and ascorbic acid (vitamin C) to the dialysate reduced oxidant stress in the in vitro experiments.…”