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- W2012691454 abstract "Adequate cellular availability of synthetic oligonucleotides is crucial to their success as therapeutic agents. These compounds, however, are not expected to be orally active. This has led to interest in a variety of alternate drug delivery methods, including iontophoretically enhanced transdermal delivery. The purpose of this work is to begin characterizing the structure-activity relationship for iontophoresis of oligonucleotides through the skin. The in vitro permeation of 16 biologically relevant phosphorothioate oligonucleotides across hairless mouse skin was studied. Oligonucleotides with less than 20 bases (n = 10) had a wide range of steady-state flux levels (2.1-26.2 pmol/ cm2 h). A lower flux differential was observed for compounds ranging from 20 to 40 bases long (1.2-2.2 pmol/cm2 h). For the smaller compounds, transport, in general, decreased with increasing size; however, there were several oligonucleotides that did not follow this pattern. These data indicate that factors other than size influence transport and that the impact is greater at shorter lengths. Differential penetration between equal sized oligonucleotides synthesized with identical bases in reversed order indicates that sequences and not simply base composition affects steady-state flux across skin. Molecular structure, therefore, is a key contributor to iontophoretically assisted transport. Further studies are necessary to develop more precise predictions about the relationship between oligonucleotide structure and transdermal delivery." @default.
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- W2012691454 date "1998-01-01" @default.
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- W2012691454 title "Effects of Size and Sequence on the lontophoretic Delivery of Oligonucleotidest" @default.
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- W2012691454 doi "https://doi.org/10.1021/js9701871" @default.
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