1989 Fiscal Year Final Research Report Summary
Synthesis and Evaluation of Polymer-Antibody Hybrid with Pharmacologically Active Domains
| Project/Area Number |
63550692
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
高分子合成
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| Research Institution | Science University of Tokyo (1989)
Tokyo Women's Medical University (1988) |
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Principal Investigator |
KATAOKA Kazunori Science University of Tokyo, Department of Materials Science, Associate Professor, 基礎工学部, 助教授 (00130245)
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| Co-Investigator(Kenkyū-buntansha) |
SAKURAI Yasuhisa Tokyo Women's Medical College, Institute of Biomedical Engineering, Professor, 医用工学研究施設, 教授 (20010027)
INOUE Shohei University of Tokyo, Department of Synthetic Chemistry, Professor, 工学部, 教授 (20010762)
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| Project Period (FY) |
1988 – 1989
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| Keywords | Missile drug / Antibody / Drug delivery system / Poly(amino acid) / Poly(ethylene glycol) / Block copolymer / Adriamycin / Polymer micelle |
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| Research Abstract |
"Missile drug" is a technique to deliver drugs selectively to the organs or tissues where a medical treatment is needed, and as a result, to inhibit the side effects of drugs. One of the most promising types of missile drug is a conjugate of antibody with drugs via intermediate carrier polymer. In a conjugate of this type, intermediate carrier polymer plays a role in connecting as much drug as possible to antibody by minimum connecting points with antibody, and consequently a highly active conjugate with minimum decrease in antigen binding capacity of antibody is obtained. We consider that molecular design of intermediate carrier polymer is critically important to obtain the best quality of this type of missile drug. From this point of view, poly(ethylene glycol)-poly(aspartic acid) block copolymer is used as an intermediate carrier polymer. Poly(ethylene glycol) chain is considered to decrease antigenicity af missile drug, and to increase water- solubility and stability in blood stream. Poly(aspartic acid) chain carriers anti-cancer drug (adriamycin) with covalent bond and is expected to be degraded after the uptake by target cells. In this research, synthesis of a novel conjugate of anti-cancer drug adriamycin, poly(ethylene glycol)-block-poly(aspartic acid), and immunoglobulin G is conducted. Poly(ethylene glycol)-block-poly(aspartic acid), binding adriamycin on the poly( aspartic acid) chain, showed an excellent water-solubility despite the introduction of a large amount of strongly hydrophobic adriamycin, and was found to form a micellar structure in aqueous salution. Efficient coupling between poly(ethylene glycol)-block-poly( aspartic acid) binding adriamycin and immunaglobulin G was achieved via disulfide linkages.
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