The long-term objective is to develop and optimize a novel, noninvasive, iontophoretic approach for clinical monitoring via the skin. The low-level current density drives both charged and highly polar (yet neutral) compounds across the skin at rates much greater than passive diffusion. As the skin offers a uniquely accessible body surface across which information can be extracted, we hypothesize that truly noninvasive and highly sensitive devices, which exploit uniquely paired flows of at least two substances, can be developed for iontophoretic monitoring applications. The research strategy will optimize iontophoretic and sensing technology to satisfy three key criteria for success: (a) fundamental understanding of electrotransport across the skin; (b) reproducible enhancement of transdermal permeability to identify clinical monitoring opportunities via the skin; and (c) characterization and validation of simple, user-friendly devices for sample collection coupled with sensitive and specific analytical tools.
The specific aims of the project are:- [1] To refine understanding of electrotransport across the skin; to exploit the interactions (and independence) of solute and ion flows in the presence of an applied electric field. [2] To demonstrate that the simultaneous, 'reverse iontophoretic' extraction of a target analyte, together with an endogenous substance of essentially constant concentration within the body, can offer truly noninvasive, clinical monitoring. [3] To engineer simple, elegant, prototypical devices, of small volume (100 mu-L or less), into which reverse iontophoretically extracted samples may be efficiently collected. [4] To couple these systems to highly sensitive and specific chromatographic and electrochemical analytical tools both off-line and, eventually, on-line, in situ. Proof-of-principle targets three analytes of significant interest: glucose, phenylalanine and lithium. Furthermore, the bioengineering and analytical chemistry advances envisaged will allow broad, 'mass-screening' of the substances extracted (and extractable) by reverse iontophoresis revealing additional opportunities for the approach. In summary, this project aims to evaluate iontophoretic bioengineering technology in vivo in man; specifically, applications with respect to clinical chemistry and therapeutic drug monitoring are foreseen.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Research Project (R01)
Project #
5R01EB001420-03
Application #
6948579
Study Section
Pharmacology A Study Section (PHRA)
Program Officer
Korte, Brenda
Project Start
2003-08-15
Project End
2008-07-31
Budget Start
2005-08-01
Budget End
2008-07-31
Support Year
3
Fiscal Year
2005
Total Cost
$243,000
Indirect Cost
Name
University of Bath
Department
Type
DUNS #
424400661
City
Bath
State
Country
United Kingdom
Zip Code
BA2 7-AY
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Bouissou, Camille C; Sylvestre, Jean-Philippe; Guy, Richard H et al. (2009) Reverse iontophoresis of amino acids: identification and separation of stratum corneum and subdermal sources in vitro. Pharm Res 26:2630-8
Sylvestre, Jean-Philippe; Guy, Richard H; Delgado-Charro, M Begona (2008) In vitro optimization of dexamethasone phosphate delivery by iontophoresis. Phys Ther 88:1177-85
Sylvestre, J-P; Diaz-Marin, C; Delgado-Charro, M B et al. (2008) Iontophoresis of dexamethasone phosphate: competition with chloride ions. J Control Release 131:41-6
Sieg, Anke; Jeanneret, Fabienne; Fathi, Marc et al. (2008) Extraction of amino acids by reverse iontophoresis: simulation of therapeutic monitoring in vitro. Eur J Pharm Biopharm 70:908-13
Russell, Lisa M; Wiedersberg, Sandra; Delgado-Charro, M Begona (2008) The determination of stratum corneum thickness: an alternative approach. Eur J Pharm Biopharm 69:861-70
Mudry, Blaise; Carrupt, Pierre-Alain; Guy, Richard H et al. (2007) Quantitative structure-permeation relationship for iontophoretic transport across the skin. J Control Release 122:165-72
Nixon, Susan; Sieg, Anke; Delgado-Charro, M B et al. (2007) Reverse iontophoresis of L-lactate: in vitro and in vivo studies. J Pharm Sci 96:3457-65
Wascotte, Valentine; Caspers, Peter; de Sterke, Johanna et al. (2007) Assessment of the ""skin reservoir"" of urea by confocal Raman microspectroscopy and reverse iontophoresis in vivo. Pharm Res 24:1897-901
Wascotte, Valentine; Delgado-Charro, M Begona; Rozet, Eric et al. (2007) Monitoring of urea and potassium by reverse iontophoresis in vitro. Pharm Res 24:1131-7

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