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Novel polymer for gene and stem cell delivery
8th International Conference and Exhibition on Pharmaceutics & Novel Drug Delivery Systems
March 07-09, 2016 Madrid, Spain
Sung Wan Kim
University of Utah, USA
Posters & Accepted Abstracts: Pharm Anal Acta
Abstract:
The disulfide-linked bioreducible polymer poly (cystaminebisacrylamide-diaminohexane) [CBA-DAH] was synthesized. Primary rat skeletal myoblasts were transfected with poly (CBA-DAH)/pCMV-VEGF165. MRI analysis of the treatment groups reveled a significant recovery of ejection fraction in the VEGF myoblast treatment over myoblasts only and ligation control. Apoptotic cell population reveled a significant attenuation of apoptosis in the myoblast only group but a higher attenuation in the VEGF myoblast group compared to ligation controls. This indicated that while myoblast implantation alone limits apoptosis in the myocardium, the VEGF myoblast group is producing a significantly higher protective effect. The work demonstrates that bioreducible polymers can successfully be used to transfect skeletal myoblasts with angiogenic factors. We proposed that the hMSCs delivered by our PLGA/PEI 1.8k (PPP) microparticles produce in-vivo cardioprotective effects on post-infarct cardiac remodeling. We demonstrated that intramyocardial delivery of hMSCs by porous PPP particles in infarcted rats preserved engraftment of hMSCs in infarcted myocardium, cardiac geometry, and left ventricular systolic function. In addition, hMSCs-loaded PPP delivery augmented blood flow to coronary artery. The reduced infarct size of hMSC-loaded PPP delivery was followed by a decrease in fibrosis, protection from cardiomyocyte loss, and down-regulation of apoptotic activity. Furthermore, the increased angiogenesis and decreased myofibroblast density in the border zone of the infarct support the beneficial effects of hMSC-loaded PPP administration. These results of hMSC therapy delivered by PPP particles provide insight into the hMSC therapy translation in the treatment of acute myocardial infarct to human trials.
Biography :
Email: SW.Kim@pharm.utah.edu