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.
Sci Transl Med. 2014 Oct 15;6(258):258ra141. doi: 10.1126/scitranslmed.3009135.
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vesicles are able to extract ionizable drugs and toxic metabolites into the peritoneal space and can be easily withdrawn from the body at the end of dialysis.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.
腹膜透析在肾功能不全患者中具有治疗优势，并且已在其他适应证中得到证实有益，例如清除过多的代谢物或过量的药物。然而，它在全球约 10%的透析患者中使用，部分原因是与血液透析相比，其清除率较低。我们开发了一种基于脂质体的透析液，具有跨膜 pH 梯度（碱性或酸性水核），可提高腹膜透析的疗效，特别是用于清除过多的代谢物或过量的药物。这些清除囊泡能够将可离子化的药物和毒性代谢物提取到腹膜腔中，并在透析结束时轻松从体内取出。这种方法成功地从患有高氨血症的大鼠中去除了氨，其提取效率高于传统的腹膜透析，因此可能对治疗严重高氨血症有用。脂质体透析还用于在大鼠的腹膜腔中浓缩外源性化合物，从而可以隔离几种在人群中经常过量使用的药物。特别是，脂质体透析在药物过量的大鼠模型中比对照透析更有效地拮抗心血管药物维拉帕米的降压作用。这些发现强调了这种基于脂质体的方法在紧急透析中的多功能性和优势。
