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

• Published in: Carbohydrate polymers Vol. 287; p. 119326
• Main Authors: Zhang, Qiuyan, Tong, Jun, Zhou, Wei, Zhong, Zibiao, Hu, Qianchao, Ma, Qiang, Long, Haitao, Wu, Shuangquan, Shi, Xiaowen, Ye, Qifa
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.07.2022
• Subjects: Amphiphilic chitosan; Anti-Bacterial Agents - pharmacology; Antioxidants - pharmacology; Chitosan - pharmacology; Hypothermic machine perfusion; Kidney; Micelles; Nanoparticles; Organ Preservation; Hypothermic machine perfusion; Amphiphilic chitosan; Organ preservation; Micelles
• ISSN: 0144-8617; 1879-1344
• DOI: 10.1016/j.carbpol.2022.119326

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. The micelles are synthesized on the basis of chitosan, and present good Alda-1 loading capacity. Application of the micelles and Alda-1 in hypothermic machine perfusion brings natural antibacterial and antioxidant properties. The micelles act directly on the mitochondria, reduce the ischemic damage and improve the function of impaired donor kidneys. [Display omitted]