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

Intercellular adhesion molecule-1 suppression in skin by topical delivery of anti-sense oligonucleotides.
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通过局部递送反义寡核苷酸抑制皮肤中的细胞间粘附分子-1。

DOI:
10.1046/j.1523-1747.2000.00143.x
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发表时间:
2000
期刊:
The Journal of investigative dermatology
影响因子:
--
通讯作者:
G. Hardee
G. Hardee
中科院分区:
--
文献类型:
--
作者:
R. Mehta;K. Stecker;S. Cooper;M. Templin;Y. Tsai;T. Condon;C. Bennett;G. Hardee

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我们局部应用20核苷酸硫代磷酸细胞间粘附分子-1反义寡脱氧核苷酸的乳膏制剂。它有效地抑制肿瘤坏死因子-α诱导的细胞间粘附分子-1在人皮肤移植到严重免疫缺陷小鼠的表达。这些作用是浓度依赖性的,序列特异性的,并且是由于皮肤中细胞间粘附分子-1 mRNA水平的降低。静脉给药未显示药理学作用,可能是由于皮肤中药物浓度不足。然而,局部给药在表皮和真皮中产生了快速和显著更高的寡脱氧核苷酸积累。结果强烈表明,局部应用的反义寡核苷酸可以被递送到皮肤中的靶位点,并且在银屑病和其他炎性皮肤疾病的治疗中可能具有相当大的价值。
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.
DOI: 10.1001/archderm.135.5.546
发表时间: 1999-05-01
影响因子: --
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