1998 Fiscal Year Final Research Report Summary
Development of the targetable and fusogenic polyethyleneglycol liposomes for gene delivery
| Project/Area Number |
08672568
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
医薬分子機能学
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| Research Institution | TEIKYO UNlVERSITY |
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Principal Investigator |
MARUYAMA Kazuo TEIKYO UNIVERSITY,School of Pharmaceutical Sciences, Associate Professor, 薬学部, 助教授 (30130040)
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| Project Period (FY) |
1996 – 1998
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| Keywords | DDS / liposome / gene therapy / polyethyleneglycol / membrane fusion / transferrin |
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| Research Abstract |
For the purpose of intracellular targeting carrier by systemic administration, PEG-liposomes conjugating transferrin (TF) at the distal ends of PEG chain were newly prepared. Biodistribution of TF-PEG liposome was examined in the colon 26 bearing mice. TF-PEG liposome were prolonged in the circulation and highly accumulated into the tumor tissue. After extravasation, TF-PEG liposome retains the specific binding ability to tumor cell surface. Uptake of TF-PEG liposome was examined by electron microscopy. TF-PEG liposome was localized at the cell surface, coated pits and endosome. These results show TF-PEG liposome was bound and internalized by endocytosis. Such liposomes should be useful for intracellular targeting carrier at the way of systemic administration.
We prepared a new fusogenic liposomes modified with succinylated poly(glycidol)(sucPG), which is a polyethyleneglycol derivatives with carboxyl groups and alkyl groups. Furthermore, we prepared sucPG immunoliposomes, which were conjugated with TF, to gain the binding and endocytotic internalization to the tumor cells. SucPG liposomes (eggPC : sucPG=4 : 1 w/w) showed fusion ability under acidic condition such as pH4.O.From the fluorescent microscopic observation, it was shown that TF-sucPG irnmunoliposomes bound to colon26 tumor cells and induced endocytosis. These results suggested the occurrence of fusion between sucPG immunoliposomes and endosome membrane. TF-sucPG immunoliposomes have targeting and fusion ability to the Colon26 tumor cells. Thus we have succeeded to develop the targetable and fusogenic liposomes. TF-sucPG immunoliposome could be useful for as a vector in gene therapy.
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