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
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.