Enhanced drug delivery systems using pH-responsive peptides and reverse electrodialysis

Abstract

The purpose of this study was to increase the efficacy and safety of drugs in the biosystem. Two methods have been used in my research. First study is giving pH-selectivity to LK peptide which is a cell penetrating peptide composed of leucine (L) and lysine (K) with high cell penetrating ability at 10 nM level. I introduced histidine (H) with a pKa of 6.0 in the sequence of the LK peptide to introduce pH-sensitivity into the peptide. As a result, I have developed a new LH peptide which can be protonated at about pH 6 and represent positive charges for the internalization into cells. The LH peptide could be used as an cancer-targeting drug carrier, because the pH around cancerous tissues is about 5-6. I confirmed that the LH peptide selectively penetrates into the cells depending on the pH. Moreover, I compared the toxicity of the LH peptide at different pH conditions. Secondly, I introduced Reverse Electrodialysis (RED) into transdermal drug delivery system. RED patch could generate the electrical energy from the ion gradient of two salt solution of different concentrations across ion-selective membranes. I used the generated electrical energy for delivering ionic drugs into skin. I confirmed that the ionic drugs were efficiently delivered by the RED system in in vitro penetration test. Finally, through a cooperative research, I examined the in vivo pharmacological effects of risedronate delivered by RED in osteoporosis-induced mouse models. I believed that both studies will be used as effective alternatives for drug delivery with high efficiency and safety in near future.