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Topical delivery of anti-sense oligonucleotides using low-frequency sonophoresis
Ahmet Tezel1, Sujatha Dokka, Susan Kelly
1Department of Chemical Engineering, University of California Santa Barbara, Santa Barbara, California 93106, USA.
Purpose:
Topical delivery of oligonucleotides, though attractive for the treatment of skin disorders, is limited by the low permeability of the stratum corneum. Herein, we assessed the potential of low-frequency ultrasound (20 kHz, 2.4 W/cm2) in delivering therapeutically significant quantities of anti-sense oligonucleotides into skin.
Methods:
Dermal penetration of oligonucleotides penetration was quantified in vitro using radiolabeled oligonucleotides.
Results:
Estimated concentrations of oligonucleotides (ODNs) in the superficial layers of the skin ranged from approximately 0.5% to 5% of the donor concentration after a 10-min application of ultrasound and ODN. Microscopic evaluations using fluorescently labeled oligonucleotides and sulforhodamine B revealed heterogeneous penetration into the skin. Heterogenous penetration led to the formation of localized transport pathways (LTPs), which occupied about 5% of the total exposed skin area. Immuno-histochemical studies using an oligonucleotide that reacts specifically with an antibody also confirmed penetration of ODNs into LTPs. Histologic studies revealed that no gross structural changes were induced in the skin due to ultrasound application.
Conclusions:
These results show successful delivery of anti-sense oligonucleotides using low-frequency ultrasound.
