NDLI: Topical Delivery of Anti-sense Oligonucleotides Using Low-Frequency Sonophoresis

Content Provider	Springer Nature Link
Author	Tezel, Ahmet Dokka, Sujatha Kelly, Susan Hardee, Gregory E. Mitragotri, Samir
Copyright Year	2004
Abstract	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/cm$^{2}$) in delivering therapeutically significant quantities of anti-sense oligonucleotides into skin.Dermal penetration of oligonucleotides penetration was quantified in vitro using radiolabeled oligonucleotides.Estimated concentrations of oligonucleotides (ODNs) in the superficial layers of the skin ranged from ~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.These results show successful delivery of anti-sense oligonucleotides using low-frequency ultrasound.
Starting Page	2219
Ending Page	2225
Page Count	7
File Format	PDF
ISSN	07248741
Journal	Pharmaceutical Research
Volume Number	21
Issue Number	12
e-ISSN	1573904X
Language	English
Publisher	Kluwer Academic Publishers-Plenum Publishers
Publisher Date	2004-12-01
Publisher Place	New York
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	inflammation ODN oligonucleotides sonophoresis topical Pharmacology/Toxicology Pharmacy Biochemistry Medical Law Biomedical Engineering
Content Type	Text
Resource Type	Article
Subject	Organic Chemistry Pharmacology Molecular Medicine Pharmacology (medical) Biotechnology Pharmaceutical Science

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