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

P. Marcelino, H.S. Marinho, M.C. Campos, A.R. Neves, C. Real, F.S. Fontes, A. Carvalho, G. Feio, M.B.F. Martins, M.L. Corvo

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

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 7 T 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 7 T 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. © 2017
Original languageEnglish
Pages (from-to)464-471
Number of pages8
JournalEuropean Journal Of Pharmaceutical Sciences
Volume109
Early online date6 Sep 2017
DOIs
Publication statusPublished - 15 Nov 2017

Fingerprint

Reperfusion Injury
Superoxide Dismutase
Microscopy
Magnetic Resonance Spectroscopy
Liver
Liposomes
Histology
Therapeutics
Biomarkers
Wounds and Injuries
Liver Transplantation
Reperfusion
Blood Vessels
Ischemia
Antioxidants

Keywords

  • Antioxidant therapy
  • Liver ischaemia/reperfusion
  • Liver transplant
  • Magnetic resonance microscopy
  • MRM
  • Nanomedicine
  • PEGylated liposomes
  • Superoxide dismutase enzymosomes
  • Targeting

Cite this

Marcelino, P. ; Marinho, H.S. ; Campos, M.C. ; Neves, A.R. ; Real, C. ; Fontes, F.S. ; Carvalho, A. ; Feio, G. ; Martins, M.B.F. ; Corvo, M.L. / Therapeutic activity of superoxide dismutase-containing enzymosomes on rat liver ischaemia-reperfusion injury followed by magnetic resonance microscopy. In: European Journal Of Pharmaceutical Sciences. 2017 ; Vol. 109. pp. 464-471.
@article{ac4b9569f4454eceb01e1260b099093c,
title = "Therapeutic activity of superoxide dismutase-containing enzymosomes on rat liver ischaemia-reperfusion injury followed by magnetic resonance microscopy",
abstract = "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 7 T 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 7 T 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. {\circledC} 2017",
keywords = "Antioxidant therapy, Liver ischaemia/reperfusion, Liver transplant, Magnetic resonance microscopy, MRM, Nanomedicine, PEGylated liposomes, Superoxide dismutase enzymosomes, Targeting",
author = "P. Marcelino and H.S. Marinho and M.C. Campos and A.R. Neves and C. Real and F.S. Fontes and A. Carvalho and G. Feio and M.B.F. Martins and M.L. Corvo",
year = "2017",
month = "11",
day = "15",
doi = "10.1016/j.ejps.2017.09.008",
language = "English",
volume = "109",
pages = "464--471",
journal = "European Journal Of Pharmaceutical Sciences",
issn = "0928-0987",
publisher = "Elsevier B.V.",

}

Therapeutic activity of superoxide dismutase-containing enzymosomes on rat liver ischaemia-reperfusion injury followed by magnetic resonance microscopy. / Marcelino, P.; Marinho, H.S.; Campos, M.C.; Neves, A.R.; Real, C.; Fontes, F.S.; Carvalho, A.; Feio, G.; Martins, M.B.F.; Corvo, M.L.

In: European Journal Of Pharmaceutical Sciences, Vol. 109, 15.11.2017, p. 464-471.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Therapeutic activity of superoxide dismutase-containing enzymosomes on rat liver ischaemia-reperfusion injury followed by magnetic resonance microscopy

AU - Marcelino, P.

AU - Marinho, H.S.

AU - Campos, M.C.

AU - Neves, A.R.

AU - Real, C.

AU - Fontes, F.S.

AU - Carvalho, A.

AU - Feio, G.

AU - Martins, M.B.F.

AU - Corvo, M.L.

PY - 2017/11/15

Y1 - 2017/11/15

N2 - 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 7 T 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 7 T 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. © 2017

AB - 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 7 T 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 7 T 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. © 2017

KW - Antioxidant therapy

KW - Liver ischaemia/reperfusion

KW - Liver transplant

KW - Magnetic resonance microscopy

KW - MRM

KW - Nanomedicine

KW - PEGylated liposomes

KW - Superoxide dismutase enzymosomes

KW - Targeting

U2 - 10.1016/j.ejps.2017.09.008

DO - 10.1016/j.ejps.2017.09.008

M3 - Article

VL - 109

SP - 464

EP - 471

JO - European Journal Of Pharmaceutical Sciences

JF - European Journal Of Pharmaceutical Sciences

SN - 0928-0987

ER -