Sequential delivery of dexamethasone and VEGF to control local tissue response for carbon nanotube fluorescence based micro-capillary implantable sensors.
In this study, we examined the in vivo pharmacological effects of the sequential delivery of dexamethasone (DX) followed by vascular endothelial growth factor (VEGF) on the immune response and localized vascular network formation around a hydrogel-coated, micro-capillary implant for single-walled carbon nanotube based fluorescence sensors. We demonstrate, for the first time, imaging of an SWNT fluorescence device implanted subcutaneously in a rat. For tissue response studies, the chick embryo chorioallantoic membrane (CAM) was used as a tissue-model for an 8-day implantation period. The average vascular density of the tissue surrounding a hydrogel-coated microdialysis capillary sensor with simultaneous, sequential, or no delivery of DX and VEGF was 1.24+/-0.35x10(-3)vessels/microm(2), 1.15+/-0.30x10(-3)vessels/microm(2) and 0.71+/-0.20x10(-3)vessels/microm(2), respectively. Calculation of the therapeutic index (vasculature/inflammation ratio), which reflects promotion of angiogenesis versus the host immune response, demonstrates that sequential DX/VEGF delivery was 60.3% and 139.3% higher than that of VEGF and DX release alone, respectively, and was also 32.1% higher when compared to simultaneous administration, proving to be a more effective strategy in utilizing the pharmacological impact of DX and VEGF around the biosensor-model implant.
Sung
Jaeyun
J
Department of Chemical and Biomolecular Engineering, University of Illinois Urbana-Champaign, 600 S. Mathews Avenue, Urbana, IL 61801, USA.
Barone
Paul W
PW
Kong
Hyunjoon
H
Strano
Michael S
MS
D000199:Actins / Q000378:metabolism; D000818:Animals; D015374:Biosensing Techniques; D001807:Blood Vessel Prosthesis; D002196:Capillaries / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002642:Chick Embryo; D049033:Chorioallantoic Membrane / Q000098:blood supply* / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D004247:DNA / Q000378:metabolism; D003907:Dexamethasone / Q000008:administration & dosage* / Q000494:pharmacology; D016503:Drug Delivery Systems / Q000379:methods*; D005453:Fluorescence; D007109:Immunity / Q000187:drug effects; D007249:Inflammation; D037742:Nanotubes, Carbon; D018919:Neovascularization, Physiologic / Q000187:drug effects; D011092:Polyethylene Glycols; D051381:Rats; D042461:Vascular Endothelial Growth Factor A / Q000008:administration & dosage* / Q000494:pharmacology
D000199:Actins; D037742:Nanotubes, Carbon; D042461:Vascular Endothelial Growth Factor A; D011092:Polyethylene Glycols; D003907:Dexamethasone; D004247:DNA