Therapeutic activity of superoxide dismutase-containing enzymosomes on rat liver ischaemia-reperfusion injury followed by magnetic resonance microscopy

Eur J Pharm Sci. 2017 Nov 15;109:464-471. doi: 10.1016/j.ejps.2017.09.008. Epub 2017 Sep 6.


Liver ischaemia-reperfusion injury (IRI) may occur during hepatic surgery and is unavoidable in liver transplantation. Superoxide dismutase enzymosomes (SOD-enzymosomes), liposomes where SOD is at the liposomal surface expressing enzymatic activity in intact form without the need of liposomal disruption, were developed with the aim of having a better insight into its antioxidant therapeutic outcome in IRI. We also aimed at validating magnetic resonance microscopy (MRM) at 7T as a tool to follow IRI. SOD-enzymosomes were characterized and tested in a rat ischaemia-reperfusion model and the therapeutic outcome was compared with conventional long circulating SOD liposomes and free SOD using biochemical liver injury biomarkers, histology and MRM. MRM results correlated with those obtained using classical biochemical biomarkers of liver injury and liver histology. Moreover, MRM images suggested that the therapeutic efficacy of both SOD liposomal formulations used was related to prevention of peripheral biliary ductular damage and disrupted vascular architecture. Therefore, MRM at 7T is a useful technique to follow IRI. SOD-enzymosomes were more effective than conventional liposomes in reducing liver ischaemia-reperfusion injury and this may be due to a short therapeutic window.

Keywords: Antioxidant therapy; Liver ischaemia/reperfusion; Liver transplant; MRM; Magnetic resonance microscopy; Nanomedicine; PEGylated liposomes; Superoxide dismutase enzymosomes; Targeting.

MeSH terms

  • Alanine Transaminase / blood
  • Animals
  • Aspartate Aminotransferases / blood
  • Liposomes
  • Liver / drug effects
  • Liver / metabolism
  • Liver / pathology
  • Magnetic Resonance Spectroscopy
  • Male
  • Microscopy / methods
  • Rats, Wistar
  • Reperfusion Injury / blood
  • Reperfusion Injury / drug therapy*
  • Reperfusion Injury / metabolism
  • Reperfusion Injury / pathology
  • Superoxide Dismutase / administration & dosage*
  • Superoxide Dismutase / therapeutic use
  • Transcription Factor RelA / metabolism
  • gamma-Glutamyltransferase / blood


  • Liposomes
  • Transcription Factor RelA
  • Superoxide Dismutase
  • gamma-Glutamyltransferase
  • Aspartate Aminotransferases
  • Alanine Transaminase