Simvastatin-loaded polymeric micelles are more effective and less toxic than conventional statins in a pre-clinical model of advanced chronic liver disease.

Jul 20, 2020

Contributor: Diana Hide,Mar Gil,Fernanda Andrade,Diana Rafael,Imma Raurell,Miren Bravo,Aurora Barberá,Jordi Gracia-Sancho,Víctor Vargas,Salvador Augustin,Joan Genescà,Simo Schwartz,Maria Martell

Simvastatin-loaded polymeric micelles are more effective and less toxic than conventional statins in a pre-clinical model of advanced chronic liver disease.

Chronic liver disease (CLD) has no effective treatments apart from reducing its complications. Simvastatin has been tested as vasoprotective drug in experimental models of CLD showing promising results, but also limiting adverse effects. Two types of Pluronic® carriers loading simvastatin (PM108-simv and PM127-simv) as a drug delivery system were developed to avoid these toxicities while increasing the therapeutic window of simvastatin. PM127-simv showed the highest rates of cell internalization in rat liver sinusoidal endothelial cells (LSEC) and significant lower toxicity than free simvastatin, improving cell phenotype. The in vivo biodistribution was mainly hepatic with 50% of the injected PM found in the liver. Remarkably, after one week of administration in a model of CLD, PM127-simv demonstrated superior effect than free simvastatin in reducing portal hypertension. Moreover, no signs of toxicity of PM127-simv were detected. Our results indicate that simvastatin targeted delivery to LSEC is a promising therapeutic approach for CLD.
Copyright © 2020. Published by Elsevier Inc.

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About The Expert

Diana Hide

Liver Unit, Department of Medicine, Hospital Universitari Vall d’Hebron, Vall d’Hebron Institut Recerca (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Instituto de Salud Carlos III, Madrid, Spain. Electronic address: diana.hide@vhir.org.

Mar Gil

Liver Unit, Department of Medicine, Hospital Universitari Vall d’Hebron, Vall d’Hebron Institut Recerca (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain. Electronic address: mar.gil@vhir.org.

Fernanda Andrade

Drug Delivery and Targeting group, CIBBIM-Nanomedicine, Vall d’Hebron Institut Recerca (VHIR), Barcelona, Spain. Electronic address: fernanda.silva@vhir.org.

Diana Rafael

Drug Delivery and Targeting group, CIBBIM-Nanomedicine, Vall d’Hebron Institut Recerca (VHIR), Barcelona, Spain; Centro de Investigación Biomédica en Red de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Instituto de Salud Carlos III, Madrid, Spain. Electronic address: diana.fernandes_de_so@vhir.org.

Imma Raurell

Liver Unit, Department of Medicine, Hospital Universitari Vall d’Hebron, Vall d’Hebron Institut Recerca (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Instituto de Salud Carlos III, Madrid, Spain. Electronic address: imma.raurell@vhir.org.

Miren Bravo

Liver Unit, Department of Medicine, Hospital Universitari Vall d’Hebron, Vall d’Hebron Institut Recerca (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Instituto de Salud Carlos III, Madrid, Spain. Electronic address: miren.bravo@vhir.org.

Aurora Barberá

Liver Unit, Department of Medicine, Hospital Universitari Vall d’Hebron, Vall d’Hebron Institut Recerca (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain. Electronic address: aurora.barbera@vhir.org.

Jordi Gracia-Sancho

Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Instituto de Salud Carlos III, Madrid, Spain; Liver Vascular Biology Research Group, IDIBAPS, Hospital Clínic, Barcelona, Spain.. Electronic address: jordi.gracia@idibaps.org.

Víctor Vargas

Liver Unit, Department of Medicine, Hospital Universitari Vall d’Hebron, Vall d’Hebron Institut Recerca (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Instituto de Salud Carlos III, Madrid, Spain. Electronic address: vvargas@vhebron.net.

Salvador Augustin

Liver Unit, Department of Medicine, Hospital Universitari Vall d’Hebron, Vall d’Hebron Institut Recerca (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Instituto de Salud Carlos III, Madrid, Spain. Electronic address: saugustin@vhebron.net.

Joan Genescà

Liver Unit, Department of Medicine, Hospital Universitari Vall d’Hebron, Vall d’Hebron Institut Recerca (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Instituto de Salud Carlos III, Madrid, Spain. Electronic address: jgenesca@vhebron.net.

Simo Schwartz

Drug Delivery and Targeting group, CIBBIM-Nanomedicine, Vall d’Hebron Institut Recerca (VHIR), Barcelona, Spain; Centro de Investigación Biomédica en Red de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Instituto de Salud Carlos III, Madrid, Spain. Electronic address: simo.schwart@vhir.org.

Maria Martell

Liver Unit, Department of Medicine, Hospital Universitari Vall d’Hebron, Vall d’Hebron Institut Recerca (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Instituto de Salud Carlos III, Madrid, Spain. Electronic address: maria.martell@vhir.org.

References

PubMed