No systemic exposure of transtympanic heparin-binding epidermal growth factor like growth factor

Abstract

Context Heparin binding epidermal growth factor like growth factor (HB-EGF) is an emerging therapeutic for the regeneration of the tympanic membrane. 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 trans tympanic injections of 5ug/ml of HB-EGF contained within a previously described novel hydrogel vehicle, while another 12 mice had intravenous delivery of 10ug/kg of HB-EGF. Intravenous blood samples were collected at 0, 3, 24, 168, 288 and 720 hours 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 trans tympanic administration group and no mice in the intravenous administration group were found to have blood level measured above that in the controls. Discussion 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.

Hybrid Hydrogel Composed of Hyaluronic Acid, Gelatin, and Extracellular Cartilage Matrix for Perforated TM Repair

“…Compared with the self-healing group, applying a composite hydrogel scaffold in the perforated TM of rats showed that it can achieve an ideal effect, and the new tissue was well connected with the surrounding natural tissue; on the contrary, the self-healing group did not achieve complete repair and the new tissue was sticky and cloudy. Peter Luke Santa Maria et al (Maria et al, 2016) combined heparin with a growth factor to repair TM defect. Although the repair effect was achieved after 2 months, the recovery of function still needed 1-4 months, and the whole tissue regeneration and function improvement had taken for half year, which was too long.…”