Liposomes in Antidote Carriers

Introduction

If heavy metals (e.g. lead, plutonium, etc.) enter the body, they can accumulate in the liver and other organs, poisoning the body and thus causing certain diseases. The use of certain chelating compounds, such as EDTA or DTPA, can dissolve metals and treat metal storage diseases. However, these chelating agents do not pass through cell membranes, which affects their effectiveness in the body. Chelating agents can be effectively detoxified if they are formulated as liposome preparations and transported to metal storage cells using the liposomes as carriers.

Characteristic

The main features of liposomes as antidote carriers include.

• In situ capture of toxic compounds, limiting their distribution and enabling their isolation.
• Improving the in vivo stability of antidote drugs and increasing bioavailability.

Application

Bertrand et al. investigated long-circulating liposomes with a pH gradient as a treatment for diltiazem poisoning. The trapping properties of the vesicles for ionisable compounds were used to sequester the drug in the blood and to limit its pharmacological effects. The experimental results show that such liposomes can alter the pharmacokinetics and pharmacodynamics of diltiazem and its metabolites, and confirm their potential for effective detoxification.

Forster et al. developed a liposome-based dialysis medium that improves the effectiveness of peritoneal dialysis in removing excess drugs and metabolites from the body. The experimental results showed that peritoneal dialysis in rats using a liposome preparation as a dialysis medium was able to isolate a variety of exogenous compounds, such as ammonia and verapamil, and concentrate them in the dialysis fluid in the peritoneal cavity. At the end of dialysis, they are drained out of the body for the purpose of toxin removal.

Petrikovics et al. reported an optimized cyanide detoxification system of liposomes co-loaded with the novel sulfur donors DTO and rhodan. It showed a stronger detoxification effect than liposomes encapsulated with DTO or rhodan alone, as a new formulation for effective antagonism of cyanide poisoning, as assessed by prophylaxis and efficacy in an in vivo model in mice.

Alipur et al. found that an IV-acetylcysteine encapsulated liposome formulation (Lipo-NAC) was more effective than conventional NAC in preventing acute acetaminophen overdose induced hepatotoxicity. The short half-life and repeated administration of the original drug as an antidote during treatment was improved.

References

1. Forster V; et al. Liposome-supported peritoneal dialysis for detoxification of drugs and endogenous metabolites. Sci Transl Med. 2014, 6(258): 258ral41.
2. Petrikovics I; et al.Optimization of liposomal lipid composition for a new, reactive sulfur donor, and in vivo efficacy studies on mice to antagonize cyanide intoxication. J Drug Deliv. 2011, 2011: 928626
3. Alipour M; et al.Therapeutic effect of liposomal-N-acetylcysteine against acetaminophen-induced hepatotoxicity. J Drug Target. 2015, 21 (5): 466-473