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Iontophoretic delivery of a telomeric oligonucleotide.
Pharm Res. 1996 Jun; 13(6):851-4.PR

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.

Authors+Show Affiliations

Department of Internal Medicine, University of Nebraska Medical Center, Omaha 68198-6260, USA.No affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

8792421

Citation

Brand, R M., and P L. Iversen. "Iontophoretic Delivery of a Telomeric Oligonucleotide." Pharmaceutical Research, vol. 13, no. 6, 1996, pp. 851-4.
Brand RM, Iversen PL. Iontophoretic delivery of a telomeric oligonucleotide. Pharm Res. 1996;13(6):851-4.
Brand, R. M., & Iversen, P. L. (1996). Iontophoretic delivery of a telomeric oligonucleotide. Pharmaceutical Research, 13(6), 851-4.
Brand RM, Iversen PL. Iontophoretic Delivery of a Telomeric Oligonucleotide. Pharm Res. 1996;13(6):851-4. PubMed PMID: 8792421.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Iontophoretic delivery of a telomeric oligonucleotide. AU - Brand,R M, AU - Iversen,P L, PY - 1996/6/1/pubmed PY - 1996/6/1/medline PY - 1996/6/1/entrez SP - 851 EP - 4 JF - Pharmaceutical research JO - Pharm Res VL - 13 IS - 6 N2 - 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. SN - 0724-8741 UR - https://www.unboundmedicine.com/medline/citation/8792421/Iontophoretic_delivery_of_a_telomeric_oligonucleotide_ L2 - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&PAGE=linkout&SEARCH=8792421.ui DB - PRIME DP - Unbound Medicine ER -