Iontophoretic delivery of a telomeric oligonucleotide.
OBJECTIVE
To evaluate the feasibility of iontophoretically enhanced transdermal delivery of a phosphorothioate oligonucleotide across hairless mouse skin.


METHODS
The phosphorothioate sequence, 5'-d(TTAGGG)-3' (TAG-6) which mimics the repeat sequence of the telomere was used as a model compound. Iontophoresis was performed on hairless mouse skin using as in vitro flow-through diffusion system. Both 5'-FITC and uniformly 35S labeled oligonucleotide were used to monitor transdermal flux.


RESULTS
Cathodal delivery of TAG-6 resulted in substantial oligonucleotide flux. The molecular label did not alter transport properties. No flux was measured with either anodal or passive delivery. The oligonucleotide was not degraded as it crossed the skin. Molecular transport was donor condition dependent, with pH and salt concentration both having significant effects. Pre-treating the skin with ethanol reduced iontophoretic transport.


CONCLUSIONS
These data demonstrate that iontophoresis can enhance transdermal flux of an intact phosphorothioate oligonucleotide and that this penetration is donor condition dependent. Furthermore, iontophoretically enhanced transdermal delivery is a feasible approach to the administration of phosphorothioate oligonucleotides.
Brand
R M
RM
Department of Internal Medicine, University of Nebraska Medical Center, Omaha 68198-6260, USA.
Iversen
P L
PL
D000279:Administration, Cutaneous; D000818:Animals; D016650:Fluorescein-5-isothiocyanate; D006863:Hydrogen-Ion Concentration; D007478:Iontophoresis; D008297:Male; D051379:Mice; D008812:Mice, Hairless; D009841:Oligonucleotides / Q000008:administration & dosage*; D009994:Osmolar Concentration; D010592:Pharmaceutic Aids; D016615:Telomere
D009841:Oligonucleotides; D010592:Pharmaceutic Aids; D016650:Fluorescein-5-isothiocyanate