Journal
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
Volume 85, Issue 3, Pages 665-672Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ejpb.2013.02.017
Keywords
Myocardial infarction; PLGA microparticles; Biocompatibility; Phagocytic uptake; Growth factors; TROMS; Cardiac drug delivery system
Categories
Funding
- MICCIN [PLE2009-0116]
- PSE SINBAD [PSS 0100000-2008-1]
- Comunidad de Trabajo de los Pirineos (CTP)
- European Union
- University of Navarra
- Caja Navarra
- UTE project CIMA
- Agencia Espariola de Cooperacion Internacional para el Desarrollo (AECID)
- [ISCIII PI050168]
- [PI10/01621]
- [CP09/00333]
- [ISCIII-RETIC RD06/0014]
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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 mu 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 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 micropartides as vehicles for delivering growth factors in the infarcted myocardium. (C) 2013 Elsevier B.V. All rights reserved.
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