Transdermal Delivery of Antisense Oligonucleotides

Transdermal delivery is an appealing method of introducing therapeutic agents because it allows medication to bypass the gastrointestinal (GI) tract. This reduces degradation by the acid and proteolytic enzymes in the gastric environment (1 ), as well hepatic first-pass elimination (2 ) and incomplete absorption due to GI motility disorders (3 ). Transdermal delivery also provides steady-state drug levels and improves patient compliance because of its extended duration. Another beneficial use of this technique is the treatment of skin disorders using local delivery of chemicals. Careful chemical design and formulation can modulate whether topically applied medications will reside within the skin or penetrate transdermally to achieve therapeutic systemic levels. The disadvantages of transdermal delivery include limited numbers of potential drug candidates due to their inability to penetrate the skin in sufficient levels, and potential irritation at the application site (4 ).