Potential use of iontophoresis for transdermal delivery of NF-kappaB decoy oligonucleotides.
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.
Hashim
Irhan Ibrahim Abu
II
Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Kumamoto 862-0973, Japan.
Motoyama
Keiichi
K
Abd-Elgawad
Abd-Elgawad Helmy
AE
El-Shabouri
Mohamed H
MH
Borg
Thanaa Mohamed
TM
Arima
Hidetoshi
H
D000279:Administration, Cutaneous; D000818:Animals; D003872:Dermatitis / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D015194:Diffusion Chambers, Culture; D004195:Disease Models, Animal; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D007478:Iontophoresis; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000235:genetics* / Q000378:metabolism; D009841:Oligonucleotides / Q000008:administration & dosage* / Q000378:metabolism; D010539:Permeability; D012333:RNA, Messenger / Q000378:metabolism; D012867:Skin / Q000378:metabolism* / Q000473:pathology; D013755:Tetradecanoylphorbol Acetate; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D016328:NF-kappa B; D009841:Oligonucleotides; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D013755:Tetradecanoylphorbol Acetate