Intercellular adhesion molecule-1 suppression in skin by topical delivery of anti-sense oligonucleotides

被引：40

作者：

Mehta, RC ^{[1
]}

Stecker, KK ^{[1
]}

Cooper, SR ^{[1
]}

Templin, MV ^{[1
]}

Tsai, YJ ^{[1
]}

Condon, TP ^{[1
]}

Bennett, CF ^{[1
]}

Hardee, GE ^{[1
]}

机构：

[1] ISIS Pharmaceut, Carlsbad, CA 92008 USA

来源：

JOURNAL OF INVESTIGATIVE DERMATOLOGY | 2000年 / 115卷 / 05期

关键词：

drug delivery; psoriasis;

D O I：

10.1046/j.1523-1747.2000.00143.x

中图分类号：

R75 [皮肤病学与性病学];

学科分类号：

100206 ;

摘要：

We topically applied 20 nucleotide phosphorothioate intercellular adhesion molecule-1 anti-sense oligodeoxynucleotide in a cream formulation. It effectively inhibited tumor necrosis factor-alpha -induced expression of intercellular adhesion molecule-1 in human skin transplanted on severe compromised immunodeficient mice. The effects were concentration dependent, sequence specific, and resulted from reduction of intercellular adhesion molecule-1 mRNA levels in the skin. Intravenous administration of the drug did not show pharmacologic effects, probably due to insufficient drug concentrations in skin. Topical delivery, however, produced a rapid and a significantly higher accumulation of oligodeoxynucleotide in the epidermis and dermis. The results strongly suggest that topically applied anti-sense oligonucleotides can be delivered to target sites in the skin and may be of considerable value in the treatment of psoriasis and other inflammatory skin disorders.

引用

页码：805 / 812

页数：8

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