The objectives of this project are (1) to mechanistically quantify the causes of flux variability during conventional constant current DC transdermal iontophoresis and (2) to overcome this problem so constant and precise iontophoretic transport can be achieved and maintained for the treatment of different diseases. Inter-subject and intra-subject variability during conventional constant current direct current (DC) transdermal iontophoresis has been noted in the literature but has not been addressed. The importance of controlling and maintaining a constant transdermal iontophoretic flux (i.e., a constant drug administration rate or constant extraction rate) has also been demonstrated in recent iontophoresis advances. An example is the new non-invasive """"""""reverse"""""""" iontophoresis blood glucose monitoring system for the management of diabetes. This new technology can improve the quality of life of diabetics but suffers from flux variability that results in long equilibration time and frequent finger-stick calibrations. For iontophoretic extraction of compounds from the body in therapeutic monitoring and systemic delivery of drugs having narrow therapeutic windows, flux variability has posed major challenges to pharmaceutical scientists and limited the potential benefit of what transdermal iontophoresis can bring to the health of the public. In the present project, we propose to test the hypothesis that flux variability is a result of the changes in skin electrical resistance accompanying pore size, pore charge, and/or pore pathway alterations during iontophoresis. We will also test a new constant skin electrical resistance approach to overcome this flux variability problem. The information obtained in this project will help pharmaceutical scientists better predict and control transdermal iontophoretic flux in systemic drug delivery and extraction of compounds from the body for the treatment, diagnosis, and monitoring of different diseases. Our results will also advance the knowledge of the transport mechanisms and the barrier properties of the skin pathways during iontophoresis for future strategy development to enhance iontophoretic transport.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
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Study Section
Pharmacology A Study Section (PHRA)
Program Officer
Okita, Richard T
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University of Utah
Schools of Pharmacy
Salt Lake City
United States
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Baswan, Sudhir; Kasting, Gerald B; Li, S Kevin et al. (2017) Understanding the formidable nail barrier: A review of the nail microstructure, composition and diseases. Mycoses 60:284-295
Baswan, Sudhir M; Li, S Kevin; LaCount, Terri D et al. (2016) Size and Charge Dependence of Ion Transport in Human Nail Plate. J Pharm Sci 105:1201-8
Baswan, Sudhir M; Li, S Kevin; Kasting, Gerald B (2016) Diffusion of uncharged solutes through human nail plate. Pharm Dev Technol 21:255-60
Chantasart, Doungdaw; Hao, Jinsong; Li, S Kevin (2013) Evaluation of skin permeation of ?-blockers for topical drug delivery. Pharm Res 30:866-77
Smith, Kelly A; Hao, Jinsong; Li, S Kevin (2011) Effects of organic solvents on the barrier properties of human nail. J Pharm Sci 100:4244-57
Ibrahim, Sarah A; Li, S Kevin (2010) Efficiency of fatty acids as chemical penetration enhancers: mechanisms and structure enhancement relationship. Pharm Res 27:115-25
Smith, Kelly A; Hao, Jinsong; Li, S Kevin (2010) Influence of pH on transungual passive and iontophoretic transport. J Pharm Sci 99:1955-67
Hao, Jinsong; Smith, Kelly A; Li, S Kevin (2010) Time-dependent electrical properties of human nail upon hydration in vivo. J Pharm Sci 99:107-18
Ibrahim, Sarah A; Li, S Kevin (2010) Chemical enhancer solubility in human stratum corneum lipids and enhancer mechanism of action on stratum corneum lipid domain. Int J Pharm 383:89-98
Smith, Kelly A; Hao, Jinsong; Li, S Kevin (2009) Effects of ionic strength on passive and iontophoretic transport of cationic permeant across human nail. Pharm Res 26:1446-55

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