2002 Fiscal Year Final Research Report Summary
Design of novel nanocapsules with target-specificity using dendrimers
| Project/Area Number |
12680839
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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 |
Biomedical engineering/Biological material science
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| Research Institution | Osaka Prefecture University |
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Principal Investigator |
KONO Kenji Osaka Prefecture University, Graduate School of Engineering, Professor, 工学研究科, 教授 (90215187)
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| Co-Investigator(Kenkyū-buntansha) |
MARUYAMA Kazuo Teikyo University, School of Pharmacy, Professor, 薬学部, 教授 (30130040)
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| Project Period (FY) |
2000 – 2002
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| Keywords | dendrimer / nanocapsule / drug delivery system / nanobiotechnology / nanomaterials / targeting / biomaterials / nanocarrier |
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| Research Abstract |
We designed and synthesized novel nanocapsules, which deliver anticancer drugs and bioactive molecules to a specific site of the body, using dendrimers. Polyamidoamine dendrimers having poly(ethylene glycol) (PEG) at every chain end were prepared and their ability to encapsulate anticancer drugs, such as adriamycin and methotrexate. We found that the PEG-modified dendrimers could encapsulate these drugs in their interior. To improve their encapsulation ability, next, we prepared PEG-modified dendrimers with a shell consisting of hydrophobic amino acid residues. These dendrimers having a hydrophobic shell showed enhanced ability for the retention of a small guest molecule rose bengal, which is used as photosensitizer for photodynamic therapy. We also prepared PEG-modified dendrimers having cysteine residues, which have thiol groups on their side chains. The cysteine-bearing dendrimer adsorbed rose bengal more strongly in a reductive environment than in an oxidative environment, because crosslink of chain ends via disulfide bond between the cysteine residues generates a shell which reduces access of rose bengal molecules into the interior of the dendrimer. This dendrimer can be used as a nanocapsule, which releases drugs in the interior of a cell, since the inside of a cell is known to be a reductive environment. In addition, we synthesized amphiphilic dendrimers which consist of the polyamidoamine dendron and two long alkyl chains as a carrier for genes. We found that the amphiphilic dendrimer could form a complex with plasmid DNA through electrostatic interaction and deliver it into mammalian cells. Because their transfection activity was higher than a widely-used cationic liposomes for this purpose, these dendrimers may be useful as a nonviral vector for gene therapy.
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