Transdermal delivery of timolol and atenolol using electroporation and iontophoresis in combination: a mechanistic approach.
OBJECTIVE
The purpose of this work was to study the effect of electroporation on iontophoretic transport of two beta-blockers, timolol (lipophilic) and atenolol (hydrophilic), and to have a better understanding of the mechanism of combination.


METHODS
The transdermal delivery of these beta-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 beta-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.
Denet
Anne-Rose
AR
Unité de Pharmacie Galénique, Université Catholique de Louvain, UCL 7320, 1200 Brussels, Belgium.
Ucakar
Bernard
B
Préat
Véronique
V
D000279:Administration, Cutaneous; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001262:Atenolol / Q000008:administration & dosage* / Q000493:pharmacokinetics; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002851:Chromatography, High Pressure Liquid; D004563:Electrochemistry; D018274:Electroporation; D006801:Humans; D066298:In Vitro Techniques; D007478:Iontophoresis; D008055:Lipids / Q000737:chemistry; D008353:Mannitol / Q000493:pharmacokinetics; D009995:Osmosis; D013056:Spectrophotometry, Ultraviolet; D013999:Timolol / Q000008:administration & dosage* / Q000493:pharmacokinetics
D000319:Adrenergic beta-Antagonists; D008055:Lipids; D008353:Mannitol; D001262:Atenolol; D013999:Timolol