Biodegradable Particulate Delivery of Vascular Endothelial Growth Factor Plasmid from Polycaprolactone/Polyethylenimine Electrospun Nanofibers for the Treatment of Myocardial Infarction

Abstract

In this study, we present nanofiber-mediated gene delivery for myocardial infarction (MI). Branched polyethylenimine cross-linked via disulfide bonds (ssPEI) complexed with vascular endothelial growth factor (VEGF) were immobilized on electrospun polycaprolactone (PCL)/polyethylenimine (PEI) nanofibers for the local expression of VEGF angiogenic factor. We studied whether the production of VEGF from myoblast cells adhering on the nanofibers has therapeutic potential for MI. In this method, the non-specific adsorption of VEGF nanoparticles to the nanofibers occurred uniformly over all of the surface area of the nanofibers, resulting in increased transgene uptake and expression in a great number of cells. The amount of DNA required for transfection was also minimal compared to bolus delivery, because the adhered DNA was directly available in the cell microenvironment, which also helps in localized delivery. Reporter genes luciferase (Luc), red fluorescence protein (RFP), and therapeutic gene VEGF were tested to evaluate the transfection efficiency of ssPEI nanoparticles immobilized on the nanofiber surface. Our results demonstrated that the delivery of therapeutic genes from biodegradable nanoparticles immobilized on the nanofiber represented minimal cytotoxicity of H9C2 myoblasts than branched PEI 25 kDa did. According to Luc assay, fluorescence microscope analysis, and reverse transcription polymerase chain reaction (RT-PCR), this vector showed high transgene expression efficiency to the reporter gene and VEGF gene. The surface-mediated delivery of the DNA nanoparticles did not adversely affect cell growth, and facilitated the transgene expression inside the cells.