바이오의약 전달시스템 개발에 관한 연구

Abstract

Various drugs including biologically-active anticancer agents, recombinant proteins, and therapeutic genes have been developed for the treatment of diseases with high lethality such as cancers, ischemic heart diseases, or brain stroke. Though recent advances in biotechnology have proposed a wide variety of biological drugs and improved the therapeutic efficacy and bioavailability of conventional drugs, there are still limitations in the use of those candidates. Poor solubility in water and side effects in normal tissues are main problems for the anticancer agents, and long-term stability remains to overcome for the use of protein therapeutics, and transfection efficiency and stability in blood are challenges in the case of gene therapy. Drug delivery systems have been considered as a solution to overcome the obstacles. Polymeric micelles or nanoparticles are well-known carriers for the delivery of therapeutic proteins or anticancer agents and cationic polymers are most studied in the field of gene delivery. In the present study, self-assembled nanoparticles, injectable thermo-reversible gel/micelle combination system, reducible cationic peptides, and injectable hydrogel were developed for the delivery of anticancer agents, 17-AAG and docetaxel, reporter luciferase gene or siRNA against vascular endothelial growth factor (VEGF), and a fusion protein of PTD-heat shock protein 27, respectively. Biophysical characteristics of the formulations were investigated and their therapeutic efficacies were evaluated in vitro as well as in vivo. Despite further challenges regarding immunogenicity, toxicity, stability of those carriers in blood, the present data will promote future applications of those drug delivery systems proposed here for versatile anticancer agents, therapeutic proteins, DNA, and siRNA.