Monday, November 23, 2015

PLGA and PEG-PLGA investigated for release of neuregulin as part of heart-attack treatment

PolySciTech Division of Akina, Inc (www.polyscitech.com) provides a wide array of biodegradable polymers including PLGA and block PEG-PLGA copolymers. Recently, these polymers have been used for development of microparticles which deliver the neuregulin growth factor into damaged heart tissue. It was found that the MPs were able to reside in the cardiac tissue and release active neuregulin for up to three months and that PEGylated PLGA resisted phagocytosis. Read more: Pascual-Gil, S., T. Simón-Yarza, E. Garbayo, F. Prosper, and M. J. Blanco-Prieto. "Tracking the In vivo release of bioactive NRG from PLGA and PEG-PLGA microparticles in infarcted hearts." Journal of Controlled Release (2015). http://www.sciencedirect.com/science/article/pii/S0168365915302236

“Abstract: The growth factor neuregulin (NRG) is one of the most promising candidates in protein therapy as potential treatment for myocardial infarction (MI). In the last few years, biomaterial based delivery systems, such as polymeric microparticles (MPs) made of poly(lactic co glycolic acid) and polyethylene glycol (PLGA and PEG–PLGA MPs), have improved the efficacy of protein therapy in preclinical studies. However, no cardiac treatment based on MPs has yet been commercialized since this is a relatively new field and total characterization of polymeric MPs remains mandatory before they reach the clinical arena. Therefore, the objective of this study was to characterize the in vivo release, bioactivity and biodegradation of PLGA and PEG–PLGA MPs loaded with biotinylated NRG in a rat model of MI. The effect of PEGylation in the clearance of the particles from the cardiac tissue was also evaluated. Interestingly, MPs were detected in the cardiac tissue for up to 12 weeks after administration. In vivo release analysis showed that bNRG was released in a controlled manner throughout the twelve week study. Moreover, the biological cardiomyocyte receptor (ErbB4) for NRG was detected in its activated form only in those animals treated with bNRG loaded MPs. On the other hand, the PEGylation strategy was effective in diminishing phagocytosis of these MPs compared to noncoated MPs in the long term (12 weeks after injection). Taking all this together, we report new evidence in favor of the use of polymeric PLGA and PEG–PLGA MPs as delivery systems for treating MI, which could be soon included in clinical trials. Keywords: Myocardial infarction; Microparticles; Protein therapy; Phagocytosis; Bioactivity; Biotinylation”


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