Local gene delivery via endovascular stents coated with dodecylated chitosan–plasmid DNA nanoparticles

Development of efficacious therapeutic strategies to prevent and inhibit the occurrences of restenosis after percutaneous transluminal coronary angioplasty is critical for the treatment of cardiovascular diseases. In this study, the feasibility and efficiency of stents coated with dodecylated chitosan–plasmid DNA nanoparticles (DCDNPs) were evaluated as scaffolds for localized and prolonged delivery of reporter genes into the diseased blood vessel wall. Dodecylated chitosan–plasmid DNA complexes formed stable positive charged nanospheres with mean diameter of approximately 90–180 nm and zeta potential of +28 ± 3 mV. As prepared DCDNPs were spray-coated on stents, a thin layer of dense DCDNPs was successfully distributed onto the metal struts of the endovascular stents as demonstrated by scanning electron microscopy. The DCDNP stents were characterized for the release kinetics of plasmid DNA, and further evaluated for gene delivery and expression both in vitro and in vivo. In cell culture, DCDNP stents containing plasmid EGFP-C1 exhibited high level of GFP expression in cells grown on the stent surface and along the adjacent area. In animal studies, reporter gene activity was observed in the region of the artery in contact with the DCDNP stents, but not in adjacent arterial segments or distal organs. The DCDNP stent provides a very promising strategy for cardiovascular gene therapy

Characterization of poly(L-lactic acid) fibers produced by melt spinning

ABSTRACT: Biodegradable poly(L-lactic acid) (PLLA) fibers were processed by a twostep melt-spinning method (melt extrusion and hot draw) from PLLA with three different viscosity-average molecular weights (494,600, 304,700, and 262,800). Before spinning, the polymer flakes were first milled into powders and dried under vacuum. Viscosity-average molecular weight of PLLA following the fabrication process was monitored. Tensile properties of as-spun and hot-drawn fibers were investigated. Morphology of the PLLA fibers was viewed under a scanning electron microscope. Crystallinity of these fibers was assessed by thermogram analysis of differential scanning calorimetry. Results showed that the extent of decrease in the viscosity-average molecular weight of PLLA dropped sharply by 13.1-19.5% during pulverization and by 39.0 -69.0% during melt-extrusion. The hot-draw process in this study had a little effect on the viscosity-average molecular weight of PLLA. Smoother fibers could be obtained for the die temperature at least 230°C for raw materials with higher crystallinity (more than 75%) and at least 220°C for raw materials with lower crystallinity (about 60%). The as-spun fibers showed crystallinity of 16.5-22.8% and the value increased to 50.3-63.7% after hot draw. Tensile moduli of the as-spun fibers were in the range of 1.2-2.4 GPa, which were raised to 3.6 -5.4 GPa after hot draw. The final PLLA fibers with 110 -160 m diameters showed tensile strengths of 300 -600 MPa