Polyethyleneimine-anchored liposomes as scavengers for improving the efficiency of protein-bound uremic toxin clearance during dialysis

Abstract

Protein-bound uremic toxins (PBUTs) are significant toxins that are closely related to the prognosis of chronic kidney disease. They cannot be effectively removed by conventional dialysis therapies due to their high albumin binding affinity. Our previous research revealed that cationic liposomes (i.e., polyethyleneimine [PEI]-decorated liposomes) could enhance the clearance of PBUTs via electrostatic interactions. However, the poor biocompatibility (hemolysis) restricted their applications in clinical dialysis treatment. Herein, we produced PEI-anchored, linoleic acid-decorated liposomes (CP-LA liposomes) via the conjugation of PEI to cholesterol chloroformate (Chol-PEI, CP), and linoleic acid (LA) was added to provide liposomal colloidal stability. The CP-LA liposomes outperformed the plain liposomes, demonstrating significantly higher PBUT binding rates and removal rates. In addition, in vitro dialysis simulation verified that the CP-LA liposomes had a better capacity for PBUT clearance than the plain liposomes, especially for PBUTs with a strong negative net charge. Hemolysis and cytotoxicity tests revealed that the biocompatibility of the CP-LA liposomes was better than that of the physically-decorated PEI-liposome. CP-LA liposomes possess great potential for PBUT clearance in clinical dialysis therapy.