الفهرس 
IntrodctionOnly 14 pages are availabe for public view
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Abstract
The field of drug delivery is developing rapidly and gaining the attention of scientists, pharmaceutical researches and industry. The development of effective drug delivery systems that can transport and deliver a drug precisely and safely to its site of action is becoming the main goal of pharmaceutical researchers. Consequently, promising ways of peptides and gene delivery have been devised. The work in this thesis involves pharmaceutical study on the potential use of hydrogel as sustained delivery system for insulin and the use of iontophoresis as a technique for enhancing the transdermal delivery of NF-κB Decoy oligonucleotides. The obtained results revealed that, The -CyD and -CyD PPRX hydrogels were formed by inserting one PEG chain in the -CyD cavity and two PEG chains in the -CyD cavity. The in vitro release study showed that the release rate of insulin from the CyDs PPRX hydrogels decreased in the order of -CyD PPRX hydrogel > -CyD PPRX hydrogel. This decrease was controlled by adjusting the concentration of CyDs in the medium. The serum insulin level after subcutaneous administration of -CyD PPRX hydrogel to rats was significantly prolonged, accompanying with an increase in the area under serum concentration-time curve, which was clearly reflected in the prolonged hypoglycemic effect. Iontophoresis increased the in vitro permeation of FITC-NF-κB decoy ODN through isolated C57BL/6 mice skin to a great extent than that obtained without iontophoresis application. The total permeated amount and the flux values of FITC-NF-κB decoy ODN were enhanced with increasing the current density and NF-κB decoy ODN concentration in the donor solution. In contrast, without iontophoresis, these values were negligible even with increasing the decoy concentration. Intact NF-κB decoy ODN were detected within the skin after 6 h iontophoresis. Fluorescence of FITC-NF-κB decoy ODN were observed at the epidermis and upper dermis by iontophoresis. On the other hand, no fluorescence was observed in the stratum corneum, when no current was applied. In mouse model of skin inflammation, iontophoretic delivery of NF-κB decoy ODN significantly reduced the increase in ear thickness caused by TPA as well as the protein and mRNA expression levels of TNF-α in the mice ears. This is the first report on transdermal delivery of decoy ODN using iontophoresis as well as the suppression of TNF-α expression by NF-κB decoy ODN introduced by iontophoresis into skin.