Liposomes to Augment Dialysis in Preclinical Models: A Structured Review

Abstract

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.

Removal of Uremic Solutes from Dialysate by Activated Carbon

“…It may also be possible to reduce solute binding to albumin by changing plasma pH or ionic strength (31,32). We have described adding powdered activated carbon to the dialysate, and others have explored adding liposomes (33,34). A potential advantage of partial regeneration of dialysate by passage through carbon block is that integration into existing dialysis circuits would be relatively simple.…”

Phosphate-Trapping Liposomes for Long-Term Management of Hyperphosphatemia

“…Several recent studies have shown use of empty liposomes (with no encapsulated drug) to passively increase extraction of endogenous toxins, in order to augment dialysis in preclinical models [ 31 ]. These include liposomes with an acidic core for extracting ammonia in hepatic failure, or cationic, linoleic acid-based, or soy-phospholipid-based liposomes for improving removal of protein-bound endogenous toxins in renal failure.…”

Liposome Formulation and In Vitro Testing in Non-Physiological Conditions Addressed to Ex Vivo Kidney Perfusion

“…The microfluidic device consists of a Y-junction, known as a staggered herringbone, followed by a staggered mixing region. The staggered herringbone structures induce rapid mixing by chaotic advection [ 30 ]. Channel 1 was loaded with PBS (pH 7.4) or BSA solution in PBS (10 mg/mL) or Myo solution in PBS buffer (0.15 mg/mL), while DSPC:Chol 50:50 ethanol solution was loaded in channel 2 (see Figure 8 b).…”