UNASSIGNED: @entity63 is a major clinical problem. Despite rigorous treatment regimes, there has been only modest success in reducing the rate of amputations in affected @entity1 . Reduced level of blood flow and enhanced @entity32 are the two major pathophysiological changes that occur in the @entity63 tissue. The objective of this study was to develop a controlled dual gene delivery system capable of delivering therapeutic plasmid eNOS and @entity688 in a temporal manner. In order to deliver multiple therapeutic genes, an @entity20043 ( @entity20043 ) based injectable system was designed. The injectable system was comprised of hollow spheres and an in situ-forming gel scaffold of @entity20043 capable of carrying gene complexes, with an extended manner release profile. In addition, the @entity20043 based injectable system was used to deliver @entity1 eNOS and @entity688 therapeutic genes in  vivo. A subcutaneous dose response study showed enhanced blood vessel density in the treatment groups of @entity688 (10   g)/eNOS (20   g) and reduced @entity32 with @entity688 (10   g) alone. Next, we carried out a hind- @entity63 model comparing the efficacy of the following interventions; Saline; @entity688 , eNOS and @entity688 /eNOS. The selected dose of eNOS, exhibited enhanced angiogenesis. @entity688 treatment groups showed reduction in the level of inflammatory cells. Furthermore, we demonstrated that eNOS up-regulated major proangiogenic growth factors such as vascular endothelial growth factors, platelet derived growth factor B, and @entity6898 , which may explain the mechanism of this approach. These factors help in formation of a stable vascular network. Thus, @entity20043 injectable system mediating non-viral delivery of @entity1 @entity688 -eNOS is a promising therapy towards treating @entity63 .

An injectable elastin-based gene delivery platform for dose-dependent modulation of angiogenesis and XXXX for critical @entity63 .

@entity1 :: ('9606', 'Species') :: ['patients', 'human'] @entity32 :: ('MESH:D007249', 'Disease') :: ['inflammation'] @entity63 :: ('MESH:D007511', 'Disease') :: ['Critical limb ischemia', 'ischemic', 'limb ischemia'] @entity20043 :: ('2516', 'Gene') :: ['elastin-like polypeptide', 'ELP'] @entity6898 :: ('2246', 'Gene') :: ['fibroblast growth factor 1'] @entity688 :: ('3586', 'Gene') :: ['IL10', 'eNOS (20   g) and IL-10', 'IL-10']
@entity32 :: (MESH:D007249,Disease) :: ['inflammation']
