1993 Fiscal Year Final Research Report Summary
Membrane Permeability and Its Improvement in Intestinal Absorption of Macromolecular Drugs
| Project/Area Number |
03671103
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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 |
応用薬理学・医療系薬学
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| Research Institution | Faculty of Pharmaceutical Sciences, Science University of Tokyo (1992-1993)
Tokyo University of Pharmacy and Life Science (1991) |
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Principal Investigator |
HAYASHI Masahiro Faculty of Pharmaceutical Sciences, Sci.Univ.of Tokyo Professor, 薬学部, 教授 (20012669)
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| Co-Investigator(Kenkyū-buntansha) |
MIZUMA Takashi Faculty of Pharmaceutical Sciences, Tokyo Coll.of Pharmacy (Associate Professor), 薬学部, 講師 (80229715)
HORIE Toshiharu Faculty of Pharmaceutical Sciences, Chiba Univ. Professor, 薬学部, 教授 (90120154)
TOMITA Mikio Faculty of Pharmaceutical Sciences, Tokyo Coll.of Pharmacy (Research Associate), 薬学部, 助手 (60207610)
KAIHO Fusao Faculty of Pharmaceutical Sciences, Sci.Univ.of Tokyo (Research Associate), 薬学部, 助手 (10120180)
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| Project Period (FY) |
1991 – 1993
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| Keywords | Absorption Enhancer / Paracellular Pathway / Polypeptide / Actomyosin / Caco-2 Cells / Caprate / Peyer's Patches / Adsorptive Endocytosis |
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| Research Abstract |
To improve the absorbability of macromolecular compounds such as polypeptides, enhancement of the paracellular transport by absorption enhancer was examined. In rat jejunum and colon, caprate (C10) induced reduction of junctional resistance and increase in menmbrane capacitance, and increased FD4K permeability, indicating C10 to be an effective paracellular enhancer. The C10 effect was inhibited by calmodulin inhibitor W7, suggesting that the effect relates to calmodulin-dependent contraction of perijunctional actomyosin. The above effects were also observed in human colon carcinoma cell lines (Caco-2). In Caco-2 cells, C10 also increased the intracellular Ca^<2+> level and W7 suppressed the increasing effect, suggesting that increase in Ca^<2+> level relates to contraction of actomyosin. Absorption of peptides across Peyer's patches (PP) was examined. More bovine serum albumin (BSA) and concanavalin A (ConA) were transported across PP than jejunal epithelium. Especially, ConA was suggested to bind to mannose binding sites on membrane surface of M cell in PP and then tranported by adsorptive endocytosis. When BSA is conjugated with ConA, the transport was observed to be increased. Preparation of PP-target microspheres including BSA or ConA is now under investigation.
In summary, in this study, useful information on the improvement of intestinal absorption of macromolecule compounds was obtained from effective application of C10 as theparacellular enhancer and PP as the absorption site.
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Research Products
(16 results)
