Enhanced drug delivery systems using pH-responsive peptides and reverse electrodialysis
pH-응답성 펩타이드와 역전기투석을 이용한 향상된 약물 전달 시스템
- 자연과학대학 화학부
- Issue Date
- 서울대학교 대학원
- pH-selectivity; Cell penetrating peptide; Reverse electrodialysis(RED); Transdermal drug delivery; Iontophoresis; Osteoporosis; Risedronate
- 학위논문 (석사)-- 서울대학교 대학원 자연과학대학 화학부, 2017. 8. 이연.
- 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.