R M Brand1, P L Iversen. 1. Department of Internal Medicine, University of Nebraska Medical Center, Omaha 68198-6260, USA.
Abstract
PURPOSE: 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.
PURPOSE: 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.
Authors: J Feng; W D Funk; S S Wang; S L Weinrich; A A Avilion; C P Chiu; R R Adams; E Chang; R C Allsopp; J Yu Journal: Science Date: 1995-09-01 Impact factor: 47.728