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Transdermal Delivery Of Timolol And Atenolol Using Electroporation And Iontophoresis In Combination: A Mechanistic Approach

Anne-Rose Denet, B. Ucakar, V. Préat
Published 2004 · Chemistry, Medicine

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AbstractPurpose. The purpose of this work was to study the effect of electroporation on iontophoretic transport of two β-blockers, timolol (lipophilic) and atenolol (hydrophilic), and to have a better understanding of the mechanism of combination. Methods. The transdermal delivery of these β-blockers through human stratum corneum was studied in three-compartment diffusion cells. The transport of mannitol was evaluated to assess the electroosmotic flow. Results. The iontophoretic transport of timolol was decreased by electroporation because the high accumulation of the lipophilic cation timolol in the stratum corneum resulted in a decrease of electroosmosis. In contrast, electroosmosis was not affected by atenolol, and the iontophoretic transport of atenolol was increased by electroporation. Conclusions. Using two different β-blockers, we showed that lipophilicity and positive charges affect the electrotransport of drugs. Understanding the effect of the physicochemical properties of the drug, as well as the electrical parameters, is thus essential for the optimization of transdermal drug delivery by a combination of electroporation and iontophoresis.
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