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Nonaqueous Gel for the Transdermal Delivery of a DTPA Penta-ethyl Ester Prodrug

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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.

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ACKNOWLEDGMENTS

The authors thank Dr. Richard Superfine and UNC Center for Computer Integrated Systems for Microscopy and Manipulation at UNC-Chapel Hill for access to the rheometer, which was funded by NIBIB/NIH award number P41-EB002025, and Dr. Joseph DeSimone for access to the differential scanning calorimeter. The authors also thank Mrs. Shraddha Shapariya for her help with pharmacokinetic studies, Dr. Jeremy Cribb for his help with the rheometer measurements, and Ms. Sara White for help with the differential scanning calorimeter. This work was funded in part by the National Institute of Health, US Department of Health and Human Services under contract HHSN266200500045C.

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Authors and Affiliations

  1. Division of Molecular Pharmaceutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, CB# 7362, 120 Mason Farm Rd, Chapel Hill, North Carolina, 27599-7362, USA

    Yong Zhang, Matthew P. Sadgrove, Katsuhiko Sueda, Yu-Tsai Yang, Erik K. Pacyniak, Russell J. Mumper & Michael Jay

  2. UNC Lineberger Comprehensive Cancer Center, Carolina Center for Cancer Nanotechnology Excellence, UNC Institute for Pharmacogenomics and Individualized Therapy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, 27599-7295, USA

    John R. Kagel, Brenda A. Braun & William C. Zamboni

  3. Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, 27599-7569, USA

    William C. Zamboni

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  1. Yong Zhang
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Correspondence to Michael Jay.

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Zhang, Y., Sadgrove, M.P., Sueda, K. et al. Nonaqueous Gel for the Transdermal Delivery of a DTPA Penta-ethyl Ester Prodrug. AAPS J 15, 523–532 (2013). https://doi.org/10.1208/s12248-013-9459-5

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