Antibacterial and antioxidant chitosan nanoparticles improve the preservation effect for donor kidneys in vitro

Abstract

Hypothermic machine perfusion (HMP) is a preferable measure to preserve kidneys from donation after cardiac death (DCD), while the current standard perfusate is imperfect. We synthesized amphiphilic chitosan, N-alkylated-O-(2-hydroxyl) propyl-3-trimethyl ammonium chitosan chloride (N-alkyl-O-HTCC) as additive in the perfusate, which can self-assembly into micelles in water (size 133 ± 8.48 nm) (ζ-potential 43.9 ± 2.06 mV), with good antibacterial activity for Escherichia coli and Staphylococcus aureus. The derivates can also deliver hydrophobic drug Alda-1 into kidneys through HMP, with drug loading ratio (~42.14%). The delivery system specifically activated mitochondrial acetaldehyde dehydrogenase 2 in kidneys and reduced the ischemic injury. What's more, the addition of N-alkyl-O-HTCC in HMP also activated mitochondria superoxide dismutase 2, presented nice antioxidant activity. These all helped to improve the quality of DCD kidneys. This study provides a feasible amphiphilic carrier for hydrophobic drugs, and provides efficient guidance for perfusate improvement.