1998 Fiscal Year Final Research Report Summary
The development of novel topical anti-cancerous chemotherapy applied with high molecular biocompetible polymer-drug complex or monoclonal antibodies.
| Project/Area Number |
08457314
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General surgery
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| Research Institution | Kinki University |
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Principal Investigator |
OHYANAGI Harumasa Kinki University, Medicine Professor, 医学部, 教授 (00030958)
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| Co-Investigator(Kenkyū-buntansha) |
HOUKI Masanori Kinki University, Medicine, Lecture, 医学部, 講師 (40278685)
KURODA Daisuke Kinki University, Medicine, Lecture, 医学部, 講師 (30248041)
NOMURA Hideaki Kinki University, Medicine, Lecture, 医学部, 講師 (20248040)
KAETSU Isao A department of science and technology, Kinki University, Professor, 理工学部, 教授 (00214247)
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| Project Period (FY) |
1996 – 1998
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| Keywords | Polymer drug complex / Monoclonal Antibody / Topical Chemotherapy / Drug Delivery System / Hepatobiliary Malignarcy / Pancreatic Malignancy / GI Tract Malignancy |
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| Research Abstract |
We have developed the clinical application of drug delivery system (DDS).
DDS with monoclonal antibodies were demonstrated to be feasible in our anti-CEA human/mouse chimeric Fab oligomers with disulfide linkages in a pancreatic-carcinoma-xenograft model.
In the development of non-invasive implantable DDS, that is , temperature dependent sol-gel transformation typeDDS, we verified that the most effective candidate was cp-polymerization of high polymer N-Lsopropilacrilamid (NIPA Am), and also elucidated that the drug release could be controlled with changing the mixture ratio of glycil metacrelate (GMA) as a co-monomer, In the animal model of athymic mouse implanted subcutaneously hepatoma cells (Alexander strain), anti-cancerous effect of this high polymer - 5FU complex was confirmed without harmful detriments to non concerous tissue.
We have also started to investigate the possibilities of the clinical use of anti-angiogenetic drug, Fumagillol derivataive (TNP-470), which is rapidly degenerated and excreted, from the body. Firstly we planted to make hydrophilic in water polymer of TNP-490. The solubility of THP49O is 2-3mp/ml and it is hydrolysed with half-life of 2-3 hours at 37ﾟC.We are trying to make the microcapsalization and emulsification of TNP-49O with oil-philic polymer, which showed to be promising. We have extended the improvement of glutamine-sheet DDS with cellulose or polylactic and alginic acid instead of polylactic and lactic acid.
In the future, we have in contemplation of DDSsystem of agonic or antagonic emzymes of superoxide or tissue fibrinolysis as anti-cancerous agents. We are, at present, certifying the activation of Mn SOD, osteopontin, fibrinolytic enzymes of cancerous and non-cancerous tissue not only in experimental but in clinical disgestive tract malignancies.
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