2003 Fiscal Year Final Research Report Summary
Development of intracellular controlled release system for optimization of gene therapy
| Project/Area Number |
13470515
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
応用薬理学・医療系薬学
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| Research Institution | Osaka University |
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Principal Investigator |
MAYUMI Tadanori Osaka University, Graduate School of Pharmaceutical Sciences, Professor, 薬学研究科, 教授 (00098485)
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| Co-Investigator(Kenkyū-buntansha) |
TSUTSUMI Yasuo Osaka University, Graduate School of Pharmaceutical Sciences, Research Associate, 薬学研究科, 助手 (50263306)
NAKAGAWA Shinsaku Osaka University, Graduate School of Pharmaceutical Sciences, Associate Professor, 薬学研究科, 助教授 (70207728)
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| Project Period (FY) |
2001 – 2003
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| Keywords | intracellular controlled release / nanoparticles / fusogenic liposomes / drug delivery system / oligonucleotide / confocal laser microscope / gene therapy |
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| Research Abstract |
In recent years, sustained or controlled drug-release system using nanospheres or microspheres is noticed in systemic pharmacokinetics. However, in the near future, not only "systemic pharmacokinetics" but also "intracellular pharmacokinetics seems to be important in Drug Delivery System research. Technology for delivering sustained release particles such as nanospheres into cytoplasm is indispensable to control the intracellular pharmacokinetics. Although some systems have been already achieved to deliver soluble drugs into cytoplasm, no system has been successful in delivering nanoparticles into cytoplasm for further sustained regulation of drug release in intracellular compartments. In this study, we established a protocol to encapsulate nanoparticles into liposomes. Additionally, the, liposomes were fur.ther fused with ultraviolet-inactivated Sendai virus in order to make fusogenic liposomes. We demonstrated that fusogenic liposomes could deliver the encapsulated nanoparticless into cytoplasm via fusion-dependent manner rather thanrendocytosis. Also nanoparticles were introduced in 94% of the 105 cells treated with fusogenic liposomes encapsulating nanoparticles. The mean number of nanoparticles introduced into cytoplasm was about 10 particles / ce11. Additionally, to evaluate intracellular slow release of drugs, nanoparticles that had adsorbed FITC-labeled oligonucleotide was introduced into the cytoplasm by fusogenic liposome. FITC-labeled oligonucleotide was confirmed to be released gradually into the cytoplasm for more than 7 days. We conclude that the technology, which can be used for the encapsulation of any functional nanoparticles, is valuable for regulation of intracellular pharmacokinetics.
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