Drug and Gene Delivery System Based on Study of Polymeric Carrier for Disease Therapy

다국어 초록 (Multilingual Abstract)

In the present study, a targeted gene carrier for αvβ3 integrin-overexpressed tumor cells was designed with widely applied materials containing water soluble chitosan(WSC), RGD peptide, and polyethyleneimine(PEI). A study of the endocytic mechanism resulted in the microtubule-dependent macropinocytosis and clathrin-mediated endocytosis. In addition, the PEI/WSC copolymer with dendrimer RGD peptide (four-branched RGD moiety) as a targeting moiety suppressed the growth of a solid tumor mass in an in vivo mouse xenograft model with PC3 cells, prostate tumor cells, by silencing BCL-2 mRNA. This result provides a good candidate with a simple and biocompatible gene carrier. On the other hand, the development of drug delivery system (DDS) for antibiotic therapy may be essential to reduce cytotoxicity and side effects of drug, and to overcome drug-resistant fungal strains. Until now, many researches have been reported to improve the therapeutic index of AmB in PEG-based, lipid-based, and polymer-based AmB formulations. However, their high cost and side effects is mainly limiting factor in public use. The aim of this study was to prove another function of the antifungal peptide as a novel ligand which targets fungal pathogens specifically in infected animal model and to investigate a synergistic action between antifungal peptide and agent. In addition, we proposed a minimum dose of antifungal agent in clinical application via pH-responsive and redox-sensitive drug carrier.