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

Citation
Rc. Mehta et al., Intercellular adhesion molecule-1 suppression in skin by topical delivery of anti-sense oligonucleotides, J INVES DER, 115(5), 2000, pp. 805-812
Citations number
47
Categorie Soggetti
Dermatology,"da verificare
Journal title
JOURNAL OF INVESTIGATIVE DERMATOLOGY
ISSN journal
0022202X → ACNP
Volume
115
Issue
5
Year of publication
2000
Pages
805 - 812
Database
ISI
SICI code
0022-202X(200011)115:5<805:IAMSIS>2.0.ZU;2-X
Abstract
We topically applied 20 nucleotide phosphorothioate intercellular adhesion molecule-1 anti-sense oligodeoxynucleotide in a cream formulation. It effec tively inhibited tumor necrosis factor-alpha -induced expression of interce llular adhesion molecule-1 in human skin transplanted on severe compromised immunodeficient mice. The effects were concentration dependent, sequence s pecific, and resulted from reduction of intercellular adhesion molecule-1 m RNA 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 high er accumulation of oligodeoxynucleotide in the epidermis and dermis. The re sults strongly suggest that topically applied anti-sense oligonucleotides c an be delivered to target sites in the skin and may be of considerable valu e in the treatment of psoriasis and other inflammatory skin disorders.