ARTÍCULO

Catheter-based intramyocardial injection of FGF1 or NRG1-loaded MPs improves cardiac function in a preclinical model of ischemia-reperfusion

Autores: Garbayo Atienza, Elisa; Gavira Gómez, Juan José; García de Yébenes Castro, Manuel; Pelacho Samper, Beatriz; Abizanda Sarasa, Gloria María; Lana Vega, Hugo; Blanco Prieto, María José; Prósper Cardoso, Felipe Luis
Título de la revista: SCIENTIFIC REPORTS
ISSN: 2045-2322
Volumen: 6
Páginas: 25932
Fecha de publicación: 2016
Lugar: WOS
Resumen:
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.