title: An evaluation of carrier agents for desferoxamine, an up-regulator of vascular endothelial growth factor.
abstract: Avascularity and hypoxia result in avascular necrosis and play a negative role in fracture healing. The FDA-approved iron chelating agent, desferoxamine (DFO) in a liquid form, has been shown to induce angiogenesis and improve fracture healing through upregulation of the vascular endothelial growth factor. We were concerned that local injection of DFO would either fail to adequately deliver sufficient drug to the desired site or lead to undesired delivery to adjacent sites. Therefore, a sustained release delivery system was desirable to direct DFO to the intended site. Calcium sulfate pellets, collagen sponges, and demineralized cortical bone matrix were all evaluated as potentially controlled release systems for DFO using a fetal mouse metatarsal angiogenesis assay. Angiogenesis was analyzed using a vascularity grading scale, by measuring the mean vessel length of the 5 longest vessels, and by counting the mean number of vessels per metatarsal. Although there was some evidence of angiogenesis with all three carriers, DFO loaded CaSO4 pellets increased vascularity grading, the mean length of the five longest vessels, and the mean number of vessels, all by statistically significant margins versus the control. These results suggest that CaSO4 pellets could be used as a viable, nontoxic, controlled release system for DFO in clinical situations where increased angiogenesis and bone growth are desirable.
authors.affiliation: University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA. brian_hertzberg@med.unc.edu
authors.forename: Brian P
authors.initials: BP
authors.lastname: Hertzberg
authors.forename: Joshua B
authors.initials: JB
authors.lastname: Holt
authors.forename: Ronald D
authors.initials: RD
authors.lastname: Graff
authors.forename: Shawn R
authors.initials: SR
authors.lastname: Gilbert
authors.forename: Laurence E
authors.initials: LE
authors.lastname: Dahners
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry; D001857:Bone Matrix / Q000737:chemistry; D002133:Calcium Sulfate / Q000737:chemistry; D003094:Collagen / Q000737:chemistry; D003676:Deferoxamine / Q000008:administration & dosage*; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems; D005260:Female; D017102:Fracture Healing / Q000187:drug effects; D006801:Humans; D051793:Hypoxia-Inducible Factor 1 / Q000378:metabolism; D008422:Materials Testing; D051379:Mice; D008810:Mice, Inbred C57BL; D018919:Neovascularization, Physiologic / Q000187:drug effects; D010020:Osteonecrosis / Q000188:drug therapy / Q000628:therapy; D011247:Pregnancy; D015854:Up-Regulation / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis*
chemical_list: D001672:Biocompatible Materials; D004337:Drug Carriers; D051793:Hypoxia-Inducible Factor 1; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D003094:Collagen; D003676:Deferoxamine; D002133:Calcium Sulfate