title: Intradermal delivery of antisense oligonucleotides by the pulse depolarization iontophoretic system.
abstract: The intradermal delivery of an antisense oligonucleotide was examined by iontophoresis. In this experiment, the antisense sequence of [(32)P]-labeled phosphodiester oligonucleotide ([(32)P]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 [(32)P]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 [(32)P]D-oligo were enhanced with the increasing current densities and [(32)P]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 [(32)P]D-oligo, and intact [(32)P]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.
authors.affiliation: School of Pharmacy, Tokyo University of Pharmacy and Life Science, Tokyo, Japan.
authors.forename: Yukihiko
authors.initials: Y
authors.lastname: Aramaki
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Arima
authors.forename: Mamiko
authors.initials: M
authors.lastname: Takahashi
authors.forename: Eriko
authors.initials: E
authors.lastname: Miyazaki
authors.forename: Takatoshi
authors.initials: T
authors.lastname: Sakamoto
authors.forename: Seishi
authors.initials: S
authors.lastname: Tsuchiya
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems / Q000379:methods*; D005260:Female; D066298:In Vitro Techniques; D007271:Injections, Intradermal; D007478:Iontophoresis / Q000379:methods*; D051379:Mice; D008812:Mice, Hairless; D016376:Oligonucleotides, Antisense / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D012867:Skin / Q000187:drug effects / Q000378:metabolism*; D012869:Skin Absorption / Q000187:drug effects / Q000502:physiology
chemical_list: D016376:Oligonucleotides, Antisense