title: Biodegradation and heart retention of polymeric microparticles in a rat model of myocardial ischemia.
abstract: Poly-lactide-co-glycolide (PLGA) microparticles emerged as one of the most promising strategies to achieve site-specific drug delivery. Although these microparticles have been demonstrated to be effective in several wound healing models, their potential in cardiac regeneration has not yet been fully assessed. The present work sought to explore PLGA microparticles as cardiac drug delivery systems. PLGA microparticles were prepared by Total Recirculation One-Machine System (TROMS) after the formation of a multiple emulsion. Microparticles of different size were prepared and characterized to select the most suitable size for intramyocardial administration. Next, the potential of PLGA microparticles for administration in the heart was assessed in a MI rat model. Particle biodegradation over time and myocardial tissue reaction were studied by routine staining and confocal microscopy. Results showed that microparticles with a diameter of 5 μm were the most compatible with intramyocardial administration in terms of injectability through a 29-gauge needle and tissue response. Particles were present in the heart tissue for up to 3 months post-implantation and no particle migration toward other solid organs was observed, demonstrating good myocardial retention. CD68 immunolabeling revealed 31%, 47% and below 4% microparticle uptake by macrophages 1 week, 1 month, and 3 months after injection, respectively (P<0.001). Taken together, these findings support the feasibility of the developed PLGA microparticles as vehicles for delivering growth factors in the infarcted myocardium.
authors.affiliation: Department of Pharmacy and Pharmaceutical Technology, School of Pharmacy, University of Navarra, Pamplona, Spain.
authors.forename: F R
authors.initials: FR
authors.lastname: Formiga
authors.forename: E
authors.initials: E
authors.lastname: Garbayo
authors.forename: P
authors.initials: P
authors.lastname: Díaz-Herráez
authors.forename: G
authors.initials: G
authors.lastname: Abizanda
authors.forename: T
authors.initials: T
authors.lastname: Simón-Yarza
authors.forename: E
authors.initials: E
authors.lastname: Tamayo
authors.forename: F
authors.initials: F
authors.lastname: Prósper
authors.forename: M J
authors.initials: MJ
authors.lastname: Blanco-Prieto
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D004655:Emulsions; D005240:Feasibility Studies; D036341:Intercellular Signaling Peptides and Proteins / Q000008:administration & dosage* / Q000493:pharmacokinetics; D019344:Lactic Acid / Q000737:chemistry*; D018613:Microscopy, Confocal; D008863:Microspheres; D017202:Myocardial Ischemia / Q000188:drug therapy* / Q000378:metabolism; D010316:Particle Size; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D051381:Rats; D013997:Time Factors; D014018:Tissue Distribution
chemical_list: D004337:Drug Carriers; D004655:Emulsions; D036341:Intercellular Signaling Peptides and Proteins; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid
keywords: Biocompatibility; Cardiac drug delivery system; Growth factors; Myocardial infarction; PLGA microparticles; Phagocytic uptake; TROMS