ESPE Abstracts (2015) 84 FC7.2

ESPE2015 Free Communications Growth-promoting therapies (6 abstracts)

TopiconThermoMatrix™-Mediated Passive Transdermal Delivery of IGF1 Across EpidermFT Full-Thickness Human Skin Equivalent: Towards an Extended-Wear IGF1 Patch

Stephen Hsu , Carl Mangleburg & Hua Yao

Prometheon Pharma, LLC, Alachua, Florida, USA

Background: There is a need for a convenient and affordable alternative to twice daily s.c. injections for children with IGF1 deficiency (IGFD) and growth failure. We report a novel platform technology, TopiconThermoMatrix™, applied to the transdermal delivery of IGF1 (7649 Da).

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 IGF1, insulin, and GH for multiple days.

Method: Lyophilized IGF1 was reconstituted in a TopiconThermoMatrix™ formulation that transitions from solid at 25 °C (room temperature) to gel at 30–32 °C (skin temperature). Formulations containing IGF1 were applied as 50 μl gel to EpidermFT™ tissue inserts, which are barrier-enhanced, full thickness, and metabolically active human skin equivalents (HSEs) when cultured in maintenance medium at 32 °C. Equal volume of medium was sampled and replenished every 24 h. IGF1 concentrations were measured by using a Quantikine® ELISA Kit (R&D Systems). Steady-state IGF1 flux (Jss) was calculated using Fick’s first law of diffusion.

Results: IGF1 TopiconThermoMatrix™ formulations over the dose range of 5–500 μg/0.6 cm2 achieved and maintained a maximum Jss of 0.8 μg/cm2 per h for 7 days. We observed a dose–response effect over the tested dose range, which was non-saturating. The calculated steady-state plasma level in pediatric IGFD patients after twice daily 0.12 mg/kg s.c. injection of Increlex™ is 250 ng/ml. Extrapolated to 7.7 l volume of distribution (30 kg boy) for Increlex (mecasermin), a 64 or 25 cm2 patch containing 500 μg/0.6 cm2 of IGF1 would achieve the target steady-state plasma level of 250 ng/ml in 1.5 or 4.5 days respectively. MTT assays showed that epidermal cell viability was preserved, independent of dose or time.

Conclusion: These rigorous in vitro studies support the feasibility of developing safe and effective extended-wear IGF1 TopiconThermoMatrix™ patches that replace daily injections and provide constant and consistent drug delivery.

Funding: This work was supported by Prometheon Pharma, LLC, which has no formal business, commercial, or other relationship with the manufacturer (Ipsen) of commercially available IGF1 (Increlex).

Article tools

My recent searches

No recent searches.