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Journal of controlled release : official journal of the Controlled Release Society (1)
Nucleic Acids Research (1)
Pharmaceutical Research (1)
Guy, Richard H. (2)
Alberti, Ingo (1)
Carrupt, Pierre-Alain (1)
Delgado-Charro, M. Begoña (1)
Fraenkel, Ernest (1)
Herkenne, Christophe (1)
Kalia, Yogeshvar N. (1)
Kayombya, Guy-Richard (1)
Mathy, François-Xavier (1)
Mudry, Blaise (1)
Naik, Aarti (1)
Préat, Véronique (1)
Romer, Katherine A. (1)
Year of Publication
Quantitative structure-permeation relationship for iontophoretic transport across the skin
Delgado-Charro, M. Begoña
Journal of controlled release : official journal of the Controlled Release Society
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 8Å. 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.
iontophoresis; skin; transport number; conductivity; structure-transport relationship
In Vivo Methods for the Assessment of Topical Drug Bioavailability
Kalia, Yogeshvar N.
This paper reviews some current methods for the in vivo assessment of local cutaneous bioavailability in humans after topical drug application. After an introduction discussing the importance of local drug bioavailability assessment and the limitations of model-based predictions, the focus turns to the relevance of experimental studies. The available techniques are then reviewed in detail, with particular emphasis on the tape stripping and microdialysis methodologies. Other less developed techniques, including the skin biopsy, suction blister, follicle removal and confocal Raman spectroscopy techniques are also described.
cutaneous bioavailability; cutaneous drug concentration; dermatopharmacokinetics; microdialysis; tape stripping
WebMOTIFS: automated discovery, filtering and scoring of DNA sequence motifs using multiple programs and Bayesian approaches
Romer, Katherine A.
Nucleic Acids Research
2007;35(Web Server issue):W217-W220.
WebMOTIFS provides a web interface that facilitates the discovery and analysis of DNA-sequence motifs. Several studies have shown that the accuracy of motif discovery can be significantly improved by using multiple de novo motif discovery programs and using randomized control calculations to identify the most significant motifs or by using Bayesian approaches. WebMOTIFS makes it easy to apply these strategies. Using a single submission form, users can run several motif discovery programs and score, cluster and visualize the results. In addition, the Bayesian motif discovery program THEME can be used to determine the class of transcription factors that is most likely to regulate a set of sequences. Input can be provided as a list of gene or probe identifiers. Used with the default settings, WebMOTIFS accurately identifies biologically relevant motifs from diverse data in several species. WebMOTIFS is freely available at http://fraenkel.mit.edu/webmotifs.
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