title: No systemic exposure of transtympanic heparin-binding epidermal growth factor like growth factor.
abstract: BACKGROUND
  Heparin-binding epidermal growth factor like growth factor (HB-EGF) is an emerging therapeutic for the regeneration of the tympanic membrane (TM).
  
  
  OBJECTIVE
  Our aim was to determine whether the doses of HB-EGF delivered in a sustained release hydrogel into a middle ear mouse model, would be measurable in the systemic circulation. We also aimed to observe, in the scenario that the intended dose was absorbed directly into the circulation, whether these levels could be measured above the background levels of HB-EGF in the circulation.
  
  
  METHODS
  A total of 12 mice had transtympanic injections of 5 μg/ml of HB-EGF contained within a previously described novel hydrogel vehicle, while another 12 mice had intravenous delivery of 10 μg/kg of HB-EGF. Intravenous blood samples were collected at 0-, 3-, 24-, 168-, 288- and 720-h post-injection. A double-antibody sandwich one-step process enzyme-linked immunosorbent assay (ELISA) was used to determine the level of HB-EGF in the serum.
  
  
  RESULTS
  No mice in the transtympanic administration group and no mice in the intravenous administration group were found to have blood level measured above that in the controls.
  
  
  CONCLUSIONS
  The inability of the positive control to measure levels above background, suggest the total dose used in our studies, even if 100% absorbed into the system circulation is insignificant.
  
  
  CONCLUSIONS
  HB-EGF at the doses and delivery method proposed for treatment of chronic TM perforation in a mouse model are likely to have no measurable systemic effect.
authors.affiliation: a Department of Otolaryngology , Head and Neck Surgery, Stanford University , Stanford , CA , USA .
authors.forename: Peter Luke
authors.initials: PL
authors.lastname: Santa Maria
authors.affiliation: b Department of Orthopedic Surgery , Stanford University , Stanford , CA , USA .
authors.forename: Sungwoo
authors.initials: S
authors.lastname: Kim
authors.affiliation: b Department of Orthopedic Surgery , Stanford University , Stanford , CA , USA .|c Department of Materials Science and Engineering , Stanford University , Stanford , CA , USA , and.|d Department of Bioengineering , Stanford University , Stanford , CA , USA.
authors.forename: Yunzhi Peter
authors.initials: YP
authors.lastname: Yang
mesh_terms: D000818:Animals; D004337:Drug Carriers / Q000737:chemistry; D004797:Enzyme-Linked Immunosorbent Assay; D066257:Heparin-binding EGF-like Growth Factor / Q000008:administration & dosage* / Q000097:blood*; D020100:Hydrogels / Q000737:chemistry; D000069555:Injection, Intratympanic; D007275:Injections, Intravenous; D008297:Male; D008808:Mice, Inbred CBA; D014018:Tissue Distribution; D014432:Tympanic Membrane / Q000187:drug effects*
chemical_list: D004337:Drug Carriers; C587884:Hbegf protein, mouse; D066257:Heparin-binding EGF-like Growth Factor; D020100:Hydrogels
keywords: Tympanic membrane; regeneration; tympanic perforation