title: Induction of angiogenesis by controlled delivery of vascular endothelial growth factor using nanoparticles.
abstract: OBJECTIVE
  The study reports the feasibility and efficiency of vascular endothelial growth factor (VEGF) delivery using nanoparticles synthesized from glycidyl methacrylated dextran (Dex-GMA) and gelatin for therapeutic angiogenesis.
  
  
  METHODS
  The nanoparticles were prepared using phase separation method, and the drug release profile was determined by ELISA study. The bioactivity of VEGF-incorporated nanoparticles (VEGF-NPs) were determined using tube formation assay. A rabbit hind limb ischemia model was employed to evaluate the in vivo therapeutic effect. Blood perfusion was measured by single-photon emission computed tomography (SPECT). Vessel formation was evaluated by contrast angiography and immunohistochemistry.
  
  
  RESULTS
  The nanoparticles synthesized were spherical in shape with evenly distributed size of about 130 ± 3.5 nm. The VEGF encapsulated was released in a biphase manner, with the majority of 69% released over 1-12 days. Tube formation assays showed increased tubular structures by VEGF-NP compared with empty nanoparticles and no treatment. Both free VEGF and VEGF-NP significantly increased blood perfusion compared with empty nanoparticles (both P < 0.001), but it was much higher in VEGF-NP-treated limbs (P < 0.001). Contrast angiography and immunohistological analysis also revealed more significant collateral artery formation and higher capillary density in VEGF-NP-treated limbs.
  
  
  CONCLUSIONS
  Dex-GMA and gelatin-based nanoparticles could provide sustained release of VEGF and may serve as a new way for angiogenesis.
authors.affiliation: Department of Cardiovascular Surgery, Xijing Hospital, The Fourth Military Medical University, Xi'an, China.
authors.forename: Jiaqi
authors.initials: J
authors.lastname: Xie
authors.forename: Haibin
authors.initials: H
authors.lastname: Wang
authors.forename: Yunya
authors.initials: Y
authors.lastname: Wang
authors.forename: Fangping
authors.initials: F
authors.lastname: Ren
authors.forename: Wei
authors.initials: W
authors.lastname: Yi
authors.forename: Kun
authors.initials: K
authors.lastname: Zhao
authors.forename: Zilin
authors.initials: Z
authors.lastname: Li
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhao
authors.forename: Zhenhua
authors.initials: Z
authors.lastname: Liu
authors.forename: Hong
authors.initials: H
authors.lastname: Wu
authors.forename: Chunhu
authors.initials: C
authors.lastname: Gu
authors.forename: Dinghua
authors.initials: D
authors.lastname: Yi
mesh_terms: D000792:Angiography; D000818:Animals; D003911:Dextrans / Q000008:administration & dosage; D005780:Gelatin / Q000008:administration & dosage; D006614:Hindlimb / Q000098:blood supply; D053758:Nanoparticles / Q000008:administration & dosage* / Q000633:toxicity; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D011817:Rabbits; D015899:Tomography, Emission-Computed, Single-Photon; D042461:Vascular Endothelial Growth Factor A / Q000008:administration & dosage*
chemical_list: D003911:Dextrans; D042461:Vascular Endothelial Growth Factor A; D005780:Gelatin