ESPE Abstracts (2014) 82 FC7.6

Topicon[trade]ThermoMatrix[trade]-Mediated Passive Transdermal Delivery of Human GH (hGH) Across EpidermFT[trade] Full-Thickness Human Skin Equivalent (HSE): Towards an Extended-Wear hGH Patch

Stephen Hsua,b, Carl Mangleburga,b & Hua Yaoa,b

aPrometheon Pharma, LLC, Alachua, Florida, USA; bSid Martin Biotechnology Institute (University of Florida), Alachua, Florida, USA

Background: There is a need for a convenient and affordable alternative to daily s.c. injections for a growing incidence and prevalence of childhood- and adult-onset human GH (hGH) deficiency.

Objective and Hypotheses: We sought to develop a convenient, non-invasive and affordable transdermal patch formulation capable of achieving passive delivery of large molecule drugs such as hGH and insulin for multiple days.

Method: Prescription lyophilized hGH was reconstituted in a Topicon™ThermoMatrix™ formulation that transitions from solid at 25 °C (room temp) to gel at 30–32 °C (skin temp). Formulations containing hGH were applied as 50 μl to EpidermFT® tissue inserts, which are mitotically and metabolically active HSEs when cultured in maintenance medium at 32 °C. Equal volume of medium was sampled and replenished every 12 h. hGH concentrations were measured by Quantikine® ELISA Kit (R&D Systems). Steady-state hGH flux (Jss) was calculated using Fick’s first law.

Results: Topicon™ThermoMatrix™ formulations over the dose range of 0.2–100 μg/06 cm2 hGH achieved and maintained a maximum Jss of 1.0 μg/cm2 per h for 7-days. We observed a dose–response with saturation at 50 μg/06 cm2. Extrapolated to 5 l human blood volume, 50 μg hGH in a <3 cm2 patch would achieve target serum Cmax of 23 or 21 ng/ml within 24 h, as observed in healthy adult male or pediatric volunteers after a single 0.03 mg/kg s.c. injection of Genotropin™ at a concentration of 5.3 mg/ml. MTT assay showed that epidermal cell viability was unaffected.

Conclusion: We report a novel platform technology, the Topicon™ThermoMatrix™TruePatch™, applied to the needleless delivery of hGH (22 kDa). These in vitro studies support the feasibility of developing safe and effective extended-wear hGH Topicon™ThermoMatrix™ patches to eliminate the need for daily injections, while providing constant and consistent drug delivery.

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