Catheter-based Intramyocardial Injection of FGF1 or NRG1-loaded MPs Improves Cardiac Function in a Preclinical Model of Ischemia-Reperfusion
Garbayo E (1,2), Gavira JJ (2,3), de Yebenes MG (2,3), Pelacho B (2,3), Abizanda G (2,3), Lana H (1,2), Blanco-Prieto MJ (1,2), Prosper F (2,3).
(1) Department of Pharmacy and Pharmaceutical Technology, School of Pharmacy, University of Navarra, Pamplona, Spain.
(2) Instituto de Investigacion Sanitaria de Navarra (IDISNA), Pamplona, Spain.
(3) Hematology, Cardiology and Cell Therapy, Clínica Universidad de Navarra and Foundation for Applied Medical Research, University of Navarra, Pamplona, Spain.
Magazine: Scientific Reports
Date: May 17, 2016Cell Therapy Area [SP] Cardiology
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.
CITATION Sci Rep. 2016 May 17;6:25932. doi: 10.1038/srep25932
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