title: Cytokine-loaded PLGA and PEG-PLGA microparticles showed similar heart regeneration in a rat myocardial infarction model.
abstract: Neuregulin (NRG1) and fibroblast growth factor (FGF1) are well known growth factors implicated in cardiomyocyte proliferation and survival, as well as in angiogenesis, the development of adult heart and the maintenance of cardiac function. NRG1 and FGF1 have become promising therapeutic agents to treat myocardial infarction (MI) disorder. Unfortunately, clinical trials performed so far reported negative efficacy results, because growth factors are rapidly degraded and eliminated from the biological tissues once administered. In order to increase their bioavailability and favour their therapeutic effects, they have been combined with poly(lactic-co-glycolic acid) and polyethylene glycol microparticles (PLGA MPs and PEG-PLGA MPs). Here we compare both types of microparticles loaded with NRG1 or FGF1 in terms of efficacy in a rat MI model. Our results showed that intramyocardial injection of NRG1 or FGF1-loaded PLGA and PEG-PLGA MPs brought about similar improvements in the ejection fraction, angiogenesis and arteriogenesis after administration into the infarcted hearts. PEG coating did not add any effect regarding MP efficacy. Both PLGA and PEG-PLGA MPs were equally phagocyted in the heart. To our knowledge, this is the first study analysing the opsonisation process in heart tissue. The results allow us to conclude that the opsonisation process is different in heart tissue compared to blood.
authors.affiliation: Pharmacy and Pharmaceutical Technology Department, School of Pharmacy, Universidad de Navarra, Pamplona, C/Irunlarrea 1, E-31080, Spain; Instituto de Investigación Sanitaria de Navarra, IdiSNA, Pamplona, C/Irunlarrea 3, E-31008 Pamplona, Spain.
authors.forename: Simon
authors.initials: S
authors.lastname: Pascual-Gil
authors.affiliation: Pharmacy and Pharmaceutical Technology Department, School of Pharmacy, Universidad de Navarra, Pamplona, C/Irunlarrea 1, E-31080, Spain.
authors.forename: Teresa
authors.initials: T
authors.lastname: Simón-Yarza
authors.affiliation: Pharmacy and Pharmaceutical Technology Department, School of Pharmacy, Universidad de Navarra, Pamplona, C/Irunlarrea 1, E-31080, Spain; Instituto de Investigación Sanitaria de Navarra, IdiSNA, Pamplona, C/Irunlarrea 3, E-31008 Pamplona, Spain.
authors.forename: Elisa
authors.initials: E
authors.lastname: Garbayo
authors.affiliation: Instituto de Investigación Sanitaria de Navarra, IdiSNA, Pamplona, C/Irunlarrea 3, E-31008 Pamplona, Spain; Hematology Service and Area of Cell Therapy, Clínica Universidad de Navarra, Foundation for Applied Medical Research, Universidad de Navarra, Pamplona, C/Irunlarrea 1, E-31080, Spain.
authors.forename: Felipe
authors.initials: F
authors.lastname: Prósper
authors.affiliation: Pharmacy and Pharmaceutical Technology Department, School of Pharmacy, Universidad de Navarra, Pamplona, C/Irunlarrea 1, E-31080, Spain; Instituto de Investigación Sanitaria de Navarra, IdiSNA, Pamplona, C/Irunlarrea 3, E-31008 Pamplona, Spain. Electronic address: mjblanco@unav.es.
authors.forename: María J
authors.initials: MJ
authors.lastname: Blanco-Prieto
mesh_terms: D000818:Animals; D016207:Cytokines; D016220:Fibroblast Growth Factor 1 / Q000008:administration & dosage*; D006321:Heart / Q000503:physiopathology; D019344:Lactic Acid / Q000737:chemistry*; D009203:Myocardial Infarction / Q000628:therapy*; D009206:Myocardium / Q000473:pathology*; D020890:Neuregulin-1 / Q000008:administration & dosage*; D011091:Polyesters / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D051381:Rats; D017207:Rats, Sprague-Dawley; D012038:Regeneration
chemical_list: D016207:Cytokines; D020890:Neuregulin-1; D011091:Polyesters; C000589473:polyethylene glycol-poly(lactide-co-glycolide); D016220:Fibroblast Growth Factor 1; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D011092:Polyethylene Glycols
keywords: Controlled release; Efficacy; Microparticles; Myocardial infarction; PEGylation; Protein therapy