Intradermal Delivery of Antisense Oligonucleotides by the Pulse Depolarization Iontophoretic System

The intradermal delivery of an antisense oligonucleotide was examined by iontophoresis. In this experiment, the antisense sequence of [32P]-labeled phosphodiester oligonucleotide ([32P]D-oligo, 18-mer) hybridizing to mouse interleukin 10 (IL-10) mRNA was used as a model D-oligo. In in vitro iontopho...

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Bibliographic Details
Published in:Biological & Pharmaceutical Bulletin 2003, Vol.26(10), pp.1461-1466
Main Authors: Aramaki, Yukihiko, Arima, Hidetoshi, Takahashi, Mamiko, Miyazaki, Eriko, Sakamoto, Takatoshi, Tsuchiya, Seishi
Format: Article
Language:English
Subjects:
Animals
antisense oligonucleotide
Biological and medical sciences
Dose-Response Relationship, Drug
Drug Delivery Systems - methods
Female
General pharmacology
hairless mouse skin
In Vitro Techniques
Injections, Intradermal
intradermal delivery
iontophoresis
Iontophoresis - methods
Medical sciences
Mice
Mice, Hairless
Oligonucleotides, Antisense - administration & dosage
Oligonucleotides, Antisense - pharmacokinetics
Pharmacokinetics. Pharmacogenetics. Drug-receptor interactions
Pharmacology. Drug treatments
Skin - drug effects
Skin - metabolism
Skin Absorption - drug effects
Skin Absorption - physiology
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Summary:The intradermal delivery of an antisense oligonucleotide was examined by iontophoresis. In this experiment, the antisense sequence of [32P]-labeled phosphodiester oligonucleotide ([32P]D-oligo, 18-mer) hybridizing to mouse interleukin 10 (IL-10) mRNA was used as a model D-oligo. In in vitro iontophoretic experiments, isolated hairless mouse skin was used with a horizontal diffusion cell. The enhancing effect of pulse depolarization (PDP) iontophoresis on the [32P]D-oligo permeation through the skin was better, and the skin irritation was less, than those of constant direct current (CDC) iontophoresis. The apparent fluxes of [32P]D-oligo were enhanced with the increasing current densities and [32P]D-oligo concentrations in the donor solution, whereas the enhanced flux decreased with the increasing NaCl concentrations in the donor solution. An optimum electric current was observed for the intradermal delivery of [32P]D-oligo, and intact [32P]D-oligo was detected within the skin after iontophoresis for 6 h. These results suggest that PDP iontophoresis may be useful for the intradermal delivery of antisense oligonucleotides.
ISSN:0918-6158
1347-5215
DOI:10.1248/bpb.26.1461