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Quantitative structure-permeation relationship for iontophoretic transport across the skin

Mudry, B.
Delgado-Charro, M. B.
Published in Journal of controlled release. 2007, vol. 122, no. 2, p. 165-172
Abstract The objective was to relate the efficiency of a charged drug to carry current across the skin during iontophoresis to its structural and/or physicochemical properties. The corollary was the establishment of a predictive relationship useful to predict the feasibility of iontophoretic drug delivery, and for the selection and optimization of drug candidates for this route of administration. A dataset of 16 cations, for which iontophoretic fluxes have been measured under identical conditions, with no competition from exogenous co-ions, was compiled. Maximum transport numbers correlated with ion mobilities and decreased with ionic size, the dependence indicating that the electromigration mechanism of iontophoresis would become negligible for drugs of hydrodynamic radius greater than about 8 A. Validation of the model was demonstrated by successfully predicting the transport numbers of three structurally distinct dipeptides, the iontophoretic data for which had been determined under distinctly different experimental conditions. Finally, for the "training" set of cations, a strong linear dependence between their transport numbers in skin and those in aqueous solution was demonstrated; the former were larger by approximately a factor of 1.4 consistent with skin's cation permselectivity. In conclusion, this research offers a practical contribution to the development of a predictive structure-transport model of iontophoresis.
Keywords Administration, CutaneousAnimalsCations/chemistry/*metabolismComputer SimulationDiffusionDiffusion Chambers, CultureDipeptides/administration & dosage/chemistry/*metabolismDrug Delivery Systems/*methodsElectric ConductivityFeasibility StudiesIontophoresisModels, BiologicalModels, ChemicalMolecular WeightPermeabilityProtein ConformationQuantitative Structure-Activity RelationshipReproducibility of ResultsSkin/*metabolismSkin AbsorptionSwine
PMID: 17707106
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MUDRY, B. et al. Quantitative structure-permeation relationship for iontophoretic transport across the skin. In: Journal of controlled release, 2007, vol. 122, n° 2, p. 165-172. doi: 10.1016/j.jconrel.2007.07.004 https://archive-ouverte.unige.ch/unige:10614

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Deposited on : 2010-08-06

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