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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