In support of ongoing research in the study of corneal and skin wound healing, we sought to improve on previously published results by using iontophoresis to deliver RNA interference-based oligonucleotides. By using a electromechanics-based approach, we were able to devise a two-phase solution that separated the buffering solution from the antisense oligonucleotide (ASO) solution. The separation was obtained by making the drug solution a higher density than the buffer, leading it to sink directly onto the tissue surface. This change immediately decreased the distance that the ASO would have to travel before delivery. The changes enabled delivery into ex vivo skin and corneas in 10 or fewer minutes and into in vivo corneas in 5 min. In vivo studies demonstrated short-term bioavailability of at least 24 h, a lack of chemical or thermal injury, a lack of interference in the healing of a corneal injury, and an antisense effect till at least day 7, but not day 14. The only side-effect observed was postdelivery edema that was not present when the vehicle alone was iontophoresed. This suggests that electro-osmotic flow from the delivery chamber was not the mechanism, but that the delivered solute likely increased the tissue's osmolarity. These results support the continued development and utilization of this ASO delivery approach in research-grade oligonucleotides to probe molecular biological pathways and in support of testing therapeutic ASOs in the skin and cornea.