| Project/Area Number |
15500314
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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 | Tokyo Medical and Dental University |
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Principal Investigator |
HORI Hisae Tokyo Medical and Dental Univ., Medical Research Institute, Assistant Professor, 難治疾患研究所, 助手 (80014190)
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| Co-Investigator(Kenkyū-buntansha) |
KUBOTA Shunichirou univ.of Tokyo, Graduate School of Arts and Science Dept.of Life Sciences, Professor, 大学院・総合文化研究科, 教授 (00260480)
YAMAGUCHI Noriko Tokyo Medical and Dental Univ., Medical Research Institute, Assistant Professor, 難治疾患研究所, 助手 (90251553)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2004: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2003: ¥2,700,000 (Direct Cost: ¥2,700,000)
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| Keywords | Collagen / in vitro translation / α1 chain / Homotrimer-gel / Drug delivery / Endostatin / Gelatin allergy |
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| Research Abstract |
The drug-delivery systems using biomaterials are important research subjects in the field of pharmacology. The collagen obtained from bovine bone and skin, has been one of the most useful carrier biomaterials for this purpose by entrapping drugs in gel formation at body temperature and for a stabilizer in vaccine. Recently, it is suggested that contamination of pathogenic prion protein would be derived from bovine bone and that gelatin allergy was caused by bovine α2 chain of type I collagen. To develop nonallergenic and pathogen-free collagen, we investigated on preparation of novel homotrimer-gel composed of human type I collagen α1 chains {α1(I)_3} in recombinant technology, and the controlled release of drugs using the collagen-gel, focusing on a new drug delivery system (DDS) in this research project. Preparation of homotrimer-gel composed of {α1(I)_3} was examined using in vitro translation methods. The cloned human α1 chain cDNA (collagenous domain, 3.2 kbp) was inserted into vectors which were used pIVEX 2.3d for bacterial expression system and pIVEX 1.3WG for wheat germ expression system. Since recombinant α1 chain protein by both expression systems showed very low yield and recovered in insoluble fraction, it needed to search more effective expression system. In drug administration study using endostatin as antiangiogenic factor, the systemic administration of endostatin had an arthritis inhibiting effect in rheumatoid arthritis animal model. In the other administration study for tumor bearing mice, the injections of atelocollagen entrapped of antisence-oligonucleotides of omithine decarboxylase (ODC) which is known to be regulator of tumor growth, showed regression of tumor in the mice. These results suggested that collagen-gel entrapped of drugs was thought to be effective new DDS.
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