| Project/Area Number |
15310093
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Nanomaterials/Nanobioscience
|
|---|
| Research Institution | Osaka University |
|---|
Principal Investigator |
NAKAGAWA Shinsaku Osaka University, Graduate School of Pharmaceutical Sciences, Associate Professor, 薬学研究科, 助教授 (70207728)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
TSUTSUMI Yasuo National Institute of Health Sciences, Osaka Branch Fundamental Research Laboratories, Project Leader, 大阪支所・医薬基盤研究施設第二プロジェクトチーム, 副プロジェクト長 (50263306)
|
|---|
| Project Period (FY) |
2003 – 2004
|
| Project Status |
Completed (Fiscal Year 2004)
|
| Budget Amount *help |
¥13,100,000 (Direct Cost: ¥13,100,000)
Fiscal Year 2004: ¥6,300,000 (Direct Cost: ¥6,300,000)
Fiscal Year 2003: ¥6,800,000 (Direct Cost: ¥6,800,000)
|
|---|
| Keywords | intracellular controlled release / nanoparticles / fusogenic liposomes / drug delivery system / oligonucleotide / confocal laser microscope / gene therapy / FACS / 共焦点レーザー顕微鏡 |
|---|
| Research Abstract |
Therapeutic agents based on DNA or RNA oligonucleotides (e.g., antisense DNA oligonucleotide, small interfering RNA) require a regulation of their kinetics in cytoplasm to maintain an optimal concentration during the treatment period. In this respect, delivery of functional nanoparticles containing the drugs into cytoplasm is thought to have a potential for the cytosolic controlled gene release. In this study, we establish a protocol for the encapsulation of nanoparticles into liposome, which is further fused with ultra violet-inactivated Sendai virus to compose fusogenic liposomes. When nanoparticles were encapsulated in conventional liposomes, endocytosis-mediated inefficient uptake of nanoparticles was observed. In contrast, nanoparticles were delivered directly and effectively into the cytoplasm by fusogenic liposome, which was mediated by a fusion-dependent but endocytosis-independent pathway. Additionally, fusogenic liposome showed a high ability to deliver nanoparticles containing DNA oligonucleotides into cytoplasm, where the oligonucleotides were gradually released from the nanoparticles. These results indicate that this combinatorial nanotechnology using fusogenic liposome and nanoparticle is valuable system for regulating the intracellular pharmacokinetics of gene-based drugs.
|
