Potential use of iontophoresis for transdermal delivery of NF-kappaB decoy oligonucleotides.

Abstract

Topical application of nuclear factor-kappaB (NF-kappaB) decoy appears to provide a novel therapeutic potency in the treatment of inflammation and atopic dermatitis. However, it is difficult to deliver NF-kappaB decoy oligonucleotides (ODN) into the skin by conventional methods based on passive diffusion because of its hydrophilicity and high molecular weight. In this study, we evaluated the in vitro transdermal delivery of fluorescein isothiocyanate (FITC)-NF-kappaB decoy ODN using a pulse depolarization (PDP) iontophoresis. In vitro iontophoretic experiments were performed on isolated C57BL/6 mice skin using a horizontal diffusion cell. The apparent flux values of FITC-NF-kappaB decoy ODN were enhanced with increasing the current density and NF-kappaB decoy ODN concentration by iontophoresis. Accumulation of FITC-NF-kappaB decoy ODN was observed at the epidermis and upper dermis by iontophoresis. In mouse model of skin inflammation, iontophoretic delivery of NF-kappaB decoy ODN significantly reduced the increase in ear thickness caused by phorbol ester as well as the protein and mRNA expression levels of tumor necrosis factor-alpha (TNF-alpha) in the mice ears. These results suggest that iontophoresis is a useful and promising enhancement technique for transdermal delivery of NF-kappaB decoy ODN.

• Authors: Irhan Ibrahim Abu Hashim, Keiichi Motoyama, Abd-Elgawad Helmy Abd-Elgawad, Mohamed H El-Shabouri, Thanaa Mohamed Borg, Hidetoshi Arima
• Journal: International journal of pharmaceutics (Int J Pharm) Vol. 393 Issue 1-2 Pg. 127-34 (Jun 30 2010) ISSN: 1873-3476 [Electronic] Netherlands
• PMID: 20417264 (Publication Type: Journal Article)
• Copyright: 2010 Elsevier B.V. All rights reserved.

Chemical References

• NF-kappa B
• Oligonucleotides
• RNA, Messenger
• Tumor Necrosis Factor-alpha
• Tetradecanoylphorbol Acetate

Topics

• Administration, Cutaneous
• Animals
• Dermatitis (genetics, metabolism, pathology, therapy)
• Diffusion Chambers, Culture
• Disease Models, Animal
• Female
• Genetic Therapy (methods)
• Iontophoresis
• Male
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• NF-kappa B (genetics, metabolism)
• Oligonucleotides (administration & dosage, metabolism)
• Permeability
• RNA, Messenger (metabolism)
• Skin (metabolism, pathology)
• Tetradecanoylphorbol Acetate
• Time Factors
• Tumor Necrosis Factor-alpha (metabolism)