title: Catheter-based Intramyocardial Injection of FGF1 or NRG1-loaded MPs Improves Cardiac Function in a Preclinical Model of Ischemia-Reperfusion.
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.
authors.affiliation: Department of Pharmacy and Pharmaceutical Technology, School of Pharmacy, University of Navarra, Pamplona, Spain.|Instituto de Investigacion Sanitaria de Navarra (IDISNA), Pamplona, Spain.
authors.forename: Elisa
authors.initials: E
authors.lastname: Garbayo
authors.affiliation: Instituto de Investigacion Sanitaria de Navarra (IDISNA), Pamplona, Spain.|Hematology, Cardiology and Cell Therapy, Clínica Universidad de Navarra and Foundation for Applied Medical Research, University of Navarra, Pamplona, Spain.
authors.forename: Juan José
authors.initials: JJ
authors.lastname: Gavira
authors.affiliation: Instituto de Investigacion Sanitaria de Navarra (IDISNA), Pamplona, Spain.|Hematology, Cardiology and Cell Therapy, Clínica Universidad de Navarra and Foundation for Applied Medical Research, University of Navarra, Pamplona, Spain.
authors.forename: Manuel Garcia
authors.initials: MG
authors.lastname: de Yebenes
authors.affiliation: Instituto de Investigacion Sanitaria de Navarra (IDISNA), Pamplona, Spain.|Hematology, Cardiology and Cell Therapy, Clínica Universidad de Navarra and Foundation for Applied Medical Research, University of Navarra, Pamplona, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Pelacho
authors.affiliation: Instituto de Investigacion Sanitaria de Navarra (IDISNA), Pamplona, Spain.|Hematology, Cardiology and Cell Therapy, Clínica Universidad de Navarra and Foundation for Applied Medical Research, University of Navarra, Pamplona, Spain.
authors.forename: Gloria
authors.initials: G
authors.lastname: Abizanda
authors.affiliation: Department of Pharmacy and Pharmaceutical Technology, School of Pharmacy, University of Navarra, Pamplona, Spain.|Instituto de Investigacion Sanitaria de Navarra (IDISNA), Pamplona, Spain.
authors.forename: Hugo
authors.initials: H
authors.lastname: Lana
authors.affiliation: Department of Pharmacy and Pharmaceutical Technology, School of Pharmacy, University of Navarra, Pamplona, Spain.|Instituto de Investigacion Sanitaria de Navarra (IDISNA), Pamplona, Spain.
authors.forename: María José
authors.initials: MJ
authors.lastname: Blanco-Prieto
authors.affiliation: Instituto de Investigacion Sanitaria de Navarra (IDISNA), Pamplona, Spain.|Hematology, Cardiology and Cell Therapy, Clínica Universidad de Navarra and Foundation for Applied Medical Research, University of Navarra, Pamplona, Spain.
authors.forename: Felipe
authors.initials: F
authors.lastname: Prosper
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D002460:Cell Line; D004195:Disease Models, Animal; D005260:Female; D016220:Fibroblast Growth Factor 1 / Q000008:administration & dosage*; D006334:Heart Function Tests / Q000187:drug effects; D007267:Injections; D019344:Lactic Acid; D008297:Male; D051379:Mice; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000503:physiopathology*; D020890:Neuregulin-1 / Q000008:administration & dosage*; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D013552:Swine; D013556:Swine, Miniature; D016896:Treatment Outcome
chemical_list: D020890:Neuregulin-1; D016220:Fibroblast Growth Factor 1; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid