Nonaqueous Gel for the Transdermal Delivery of a DTPA Penta-ethyl Ester Prodrug
Journal Title: The AAPS Journal - Year 2013, Vol 15, Issue 2
Abstract
Diethylenetriamine pentaacetic acid penta-ethyl ester, designated as C2E5, was successfully incorporated into a nonaqueous gel for transdermal delivery. The thermal and rheological properties of a formulation containing 40% C2E5, 20% ethyl cellulose, and 40% Miglyol 840® prepared using the solvent evaporation method demonstrated that the gel had acceptable content uniformity and flow properties. In vitro studies showed that C2E5 was steadily released from the gel at a rate suitable for transdermal delivery. Topical application of the gel at a 200 mg C2E5/kg dose level in rats achieved significantly higher plasma exposures of several active metabolites compared with neat C2E5 oil at the same dose level. The results suggest that transdermal delivery of a chelator prodrug is an effective radionuclide decorporation strategy by delivering chelators to the circulation with a pharmacokinetic profile that is more consistent with the biokinetic profile of transuranic elements in contaminated individuals.
Authors and Affiliations
Yong Zhang, Matthew P. Sadgrove, Katsuhiko Sueda, Yu-Tsai Yang, Erik K. Pacyniak, John R. Kagel, Brenda A. Braun, William C. Zamboni, Russell J. Mumper, Michael Jay
Keywords
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