Hart Kevin, Harvey Martyn, Tang Mingtan, Wu Zimei, Cave Grant
Intensive Care Unit, Hawkes Bay District Health Board, Hastings 9014, New Zealand.
Waikato Hospital Emergency Department, Waikato District Health Board, Hamilton 3240, New Zealand.
Pharmaceutics. 2021 Mar 16;13(3):395. doi: 10.3390/pharmaceutics13030395.
In recent years, a number of groups have been investigating the use of "empty" liposomes with no drug loaded as scavengers both for exogenous intoxicants and endogenous toxic molecules. Preclinical trials have demonstrated that repurposing liposomes to sequester such compounds may prove clinically useful. The use of such "empty" liposomes in the dialysate during dialysis avoids recognition by complement surveillance, allowing high doses of liposomes to be used. The "reach" of dialysis may also be increased to molecules that are not traditionally dialysable. We aim to review the current literature in this area with the aims of increasing awareness and informing further research. A structured literature search identified thirteen papers which met the inclusion criteria. Augmenting the extraction of ammonia in hepatic failure with pH-gradient liposomes with acidic centres in peritoneal dialysis is the most studied area, with work progressing toward phase one trials. Liposomes used to augment the removal of exogenous intoxicants and protein-bound uraemic and hepatic toxins that accumulate in these organ failures and liposome-supported enzymatic dialysis have also been studied. It is conceivable that liposomes will be repurposed from the role of pharmaceutical vectors to gain further indications as clinically useful nanomedical antidotes/treatments within the next decade.
近年来,一些研究团队一直在研究将未装载药物的“空”脂质体用作清除剂,以清除外源性毒物和内源性毒性分子。临床前试验表明,将脂质体重新用于隔离此类化合物可能具有临床应用价值。在透析过程中,在透析液中使用此类“空”脂质体可避免补体监测的识别,从而能够使用高剂量的脂质体。透析的“作用范围”还可能扩大到传统上不可透析的分子。我们旨在综述该领域的现有文献,以提高认识并为进一步研究提供信息。一项结构化文献检索确定了13篇符合纳入标准的论文。在腹膜透析中,使用具有酸性中心的pH梯度脂质体增强肝衰竭时氨的清除是研究最多的领域,相关研究正在朝着一期试验推进。用于增强清除在这些器官衰竭中蓄积的外源性毒物以及与蛋白质结合的尿毒症和肝毒素的脂质体,以及脂质体支持的酶促透析也已得到研究。可以想象,在未来十年内,脂质体将从药物载体的角色转变,获得更多作为临床有用的纳米医学解毒剂/治疗方法的适应证。