ARTÍCULO

Biodegradation and heart retention of polymeric microparticles in a rat model of myocardial ischemia

Autores: Rocha Formiga, Fabio; Garbayo Atienza, Elisa; Díaz Herráez, Paula; Abizanda Sarasa, Gloria María; Simón Yarza, María Teresa; Tamayo Revuelta, Esther; Prósper Cardoso, Felipe Luis; Blanco Prieto, María José
Título de la revista: EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
ISSN: 0939-6411
Volumen: 85
Número: 3
Páginas: 665 - 672
Fecha de publicación: 2013
Resumen:
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¿m 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 3months 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 1week, 1month, and 3months 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.