AUTHOR=Liu Guang , Fang Zhiwei , Yuan Minglu , Li Weimin , Yang Yunqi , Jiang Mier , Ouyang Yuanming , Yuan Weien
TITLE=Biodegradable Carriers for Delivery of VEGF Plasmid DNA for the Treatment of Critical Limb Ischemia
JOURNAL=Frontiers in Pharmacology
VOLUME=8
YEAR=2017
URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2017.00528
DOI=10.3389/fphar.2017.00528
ISSN=1663-9812
ABSTRACT=
The safe and efficient delivery of therapeutic nucleic acid is a prerequisite for an effective DNA therapy. In this study, we condensed the low molecular weight polyethylenimine (PEI, 1.8k Da) with 2,6-pyridinedicarboxaldehyde (PDA), both of which are degradable in vivo, to synthesize a biodegradable polycationic material (PDAPEI) to deliver vascular endothelial growth factor (VEGF) plasmid DNA (pDNA). Particle size and zeta potential of this novel degradable PEI derivatives-pDNA nanoparticle were investigated and in vitro cytotoxicity was estimated on human umbilical vein endothelial cells (HUVECs). Using pDNA-encoding VEGF-A and green fluorescence protein (GFP), we also checked transfection efficiency of the vector (PDAPEI) and found its excellent performance at 40 w/w ratio. We successfully established peripheral ischemia animal model on C57/BL6J mice to evaluate the therapeutic effect of PDAPEI/pVEGF-A polyplex system on ischemic disease and a conclusion was made that PDAPEI is a promising gene vector in the treatment of peripheral ischemic artery disease (PAD).