title: Mitotic and antiapoptotic effects of nanoparticles coencapsulating human VEGF and human angiopoietin-1 on vascular endothelial cells.
abstract: BACKGROUND
  Research towards the application of nanoparticles as carrier vehicles for the delivery of therapeutic agents is increasingly gaining importance. The angiogenic growth factors, human vascular endothelial growth factor (VEGF) and human angiopoietin-1 are known to prevent vascular endothelial cell apoptosis and in fact to stimulate human vascular endothelial cell (HUVEC) proliferation. This paper aims to study the combined effect of these bioactive proteins coencapsulated in human serum albumin nanoparticles on HUVECs and to evaluate the potential application of this delivery system towards therapeutic angiogenesis.
  
  
  RESULTS
  The angiogenic proteins, human VEGF and human angiopoietin-1, were coencapsulated in albumin nanoparticles for better controlled delivery of the proteins. The application of a nanoparticle system enabled efficient and extended-release kinetics of the proteins. The size of the nanoparticles crosslinked with glutaraldehyde was 101.0 ± 0.9 nm and the zeta potential was found to be -18 ± 2.9 mV. An optimal concentration of glutaraldehyde for the nanoparticle coating process was determined, and this provided stable and less toxic nanoparticles as protein carriers. The results of the study indicate that nanoparticles crosslinked with glutaraldehyde produced nanoparticles with tolerable toxicity which provided efficient and controlled release of the coencapsulated proteins. The nanoparticles were incubated for two weeks to determine the release profiles of the proteins. At the end of the two-week incubation period, it was observed that 49% ± 1.3% of human angiopoietin-1 and 59% ± 2.1% of human VEGF had been released from the nanoparticles. The proliferation and percent apoptosis of the HUVECs in response to released proteins was observed.
  
  
  CONCLUSIONS
  The results indicate that the released proteins were biologically active and the combined application of both the proteins demonstrated a significant highly proliferative and antiapoptotic effect on HUVECs as compared with the effect demonstrated by the individual proteins released. These studies could serve as a basis to encourage further research into the potential in vivo application of these protein-loaded nanoparticles in the field of therapeutic angiogenesis.
authors.affiliation: Biomedical Technology and Cell Therapy Research Laboratory, Department of Biomedical Engineering Faculty of Medicine, McGill University, 3775 University Street, Montreal, Québec, Canada.
authors.forename: Afshan Afsar
authors.initials: AA
authors.lastname: Khan
authors.forename: Arghya
authors.initials: A
authors.lastname: Paul
authors.forename: Sana
authors.initials: S
authors.lastname: Abbasi
authors.forename: Satya
authors.initials: S
authors.lastname: Prakash
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000008:administration & dosage / Q000737:chemistry; D042683:Angiopoietin-1 / Q000008:administration & dosage* / Q000737:chemistry; D017209:Apoptosis / Q000187:drug effects*; D001672:Biocompatible Materials / Q000737:chemistry; D049109:Cell Proliferation / Q000187:drug effects; D016503:Drug Delivery Systems / Q000379:methods*; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D005976:Glutaral / Q000737:chemistry; D006801:Humans; D008856:Microscopy, Fluorescence; D058726:Nanoconjugates / Q000737:chemistry*; D044968:Regenerative Medicine; D042461:Vascular Endothelial Growth Factor A / Q000008:administration & dosage* / Q000737:chemistry
chemical_list: D043925:Angiogenesis Inducing Agents; D042683:Angiopoietin-1; D001672:Biocompatible Materials; D058726:Nanoconjugates; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D005976:Glutaral