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Catheter-based Intramyocardial Injection of FGF1 or NRG1-loaded MPs Improves Cardiac Function in a Preclinical Model of Ischemia-Reperfusion.
Garbayo, Elisa; Gavira, Juan José; de Yebenes, Manuel Garcia; Pelacho, Beatriz; Abizanda, Gloria; Lana, Hugo; Blanco-Prieto, María José; Prosper, Felipe.
Afiliación
  • Garbayo E; Department of Pharmacy and Pharmaceutical Technology, School of Pharmacy, University of Navarra, Pamplona, Spain.
  • Gavira JJ; Instituto de Investigacion Sanitaria de Navarra (IDISNA), Pamplona, Spain.
  • de Yebenes MG; Instituto de Investigacion Sanitaria de Navarra (IDISNA), Pamplona, Spain.
  • Pelacho B; Hematology, Cardiology and Cell Therapy, Clínica Universidad de Navarra and Foundation for Applied Medical Research, University of Navarra, Pamplona, Spain.
  • Abizanda G; Instituto de Investigacion Sanitaria de Navarra (IDISNA), Pamplona, Spain.
  • Lana H; Hematology, Cardiology and Cell Therapy, Clínica Universidad de Navarra and Foundation for Applied Medical Research, University of Navarra, Pamplona, Spain.
  • Blanco-Prieto MJ; Instituto de Investigacion Sanitaria de Navarra (IDISNA), Pamplona, Spain.
  • Prosper F; Hematology, Cardiology and Cell Therapy, Clínica Universidad de Navarra and Foundation for Applied Medical Research, University of Navarra, Pamplona, Spain.
Sci Rep ; 6: 25932, 2016 05 17.
Article en En | MEDLINE | ID: mdl-27184924
ABSTRACT
Cardiovascular protein therapeutics such as neuregulin (NRG1) and acidic-fibroblast growth factor (FGF1) requires new formulation strategies that allow for sustained bioavailability of the drug in the infarcted myocardium. However, there is no FDA-approved injectable protein delivery platform due to translational concerns about biomaterial administration through cardiac catheters. We therefore sought to evaluate the efficacy of percutaneous intramyocardial injection of poly(lactic-co-glycolic acid) microparticles (MPs) loaded with NRG1 and FGF1 using the NOGA MYOSTAR injection catheter in a porcine model of ischemia-reperfusion. NRG1- and FGF1-loaded MPs were prepared using a multiple emulsion solvent-evaporation technique. Infarcted pigs were treated one week after ischemia-reperfusion with MPs containing NRG1, FGF1 or non-loaded MPs delivered via clinically-translatable percutaneous transendocardial-injection. Three months post-treatment, echocardiography indicated a significant improvement in systolic and diastolic cardiac function. Moreover, improvement in bipolar voltage and decrease in transmural infarct progression was demonstrated by electromechanical NOGA-mapping. Functional benefit was associated with an increase in myocardial vascularization and remodeling. These findings in a large animal model of ischemia-reperfusion demonstrate the feasibility and efficacy of using MPs as a delivery system for growth factors and provide strong evidence to move forward with clinical studies using therapeutic proteins combined with catheter-compatible biomaterials.
Asunto(s)

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Daño por Reperfusión Miocárdica / Factor 1 de Crecimiento de Fibroblastos / Neurregulina-1 Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Año: 2016 Tipo del documento: Article

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Daño por Reperfusión Miocárdica / Factor 1 de Crecimiento de Fibroblastos / Neurregulina-1 Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Año: 2016 Tipo del documento: Article