1994 Fiscal Year Final Research Report Summary
Development of Novel Anticancer Drug-Carriers Targetable to Tumor Blood Vessels.
| Project/Area Number |
04557072
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| Research Category |
Grant-in-Aid for Developmental Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Urology
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| Research Institution | Akita University |
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Principal Investigator |
KATO Tetsuro Akita University, School of Medicine, Associate Professor, 医学部, 助教授 (40004642)
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| Co-Investigator(Kenkyū-buntansha) |
OKADA Hiroaki Takeda Pharmaceutical Company, Researcher-in-Chief, 主任研究員
MATSUDA Yukihisa Akita University, School of Medicine, Associate Professor, 医学部, 助教授 (50157327)
SATO Kazunari Akita University, School of Medicine, Assistant, 医学部, 助手
SUZUKI Toshio Akita University, School of Medicine, Professor, 医学部, 教授 (20108559)
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| Project Period (FY) |
1992 – 1994
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| Keywords | Anticancer drug / Carrier / Tumor vessels / Ethylcellulose / Polylactic acid / Triglyceride / Hematoporphyrin |
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| Research Abstract |
The most effective approach to enhance the anticancer drugs is the restrive distribution in the tumor vascular beds and the controlled release of the available drugs. This can be achieved by using drug-carrier complexes. Though a variety carriers have been proposed, none of them saticefy the practical use in respect to drug loading rate, particle size, drug release rate and/or stability in storage. This research was designed to improve these problems of drug carriers.
Ethylcellulose microcapsule. The advantage of this carrier is ; 1) simple processes for preparation based on the principle of coacervation, 2) wide availability for water-soluble drugs, 3) high drug loading rate upto 80%, 4) controlability of drug release rate, and 5) stability in storage at room temparature. While, the inevitable disadvantage is the difficulty to produce a particle size of smaller than 100 um. To overcome this problem, we developed a new method to obtain a large quantity of small microcapsules (<100um) .
… More
With this new product, small tumorfeeding arteries become the target of microcapsule chemoembolization.
Polylactic microsphere. Preparation of microspheres with copoly (DL-lactic /glycolic acid was developed using an in-water drying emulsion method. This microsphere effectively conjugate oil-soluble drugs. An antiangiogenetic drug, TNP-470 (a derivative of fumagillin) , proved to be prepared as polylactic microspheres and exert an antitumor effect on VX2 tumors in rabbits.
Triqlyceride (oily carrier) . TNP-470 dissolved in triglyceride solution (MIGLYOL) exerted an enchanced antitumor effect due to the prolonged drug-release as well as the stability as compared with the conventional oily carriers such as sexame oil and lipiodol. MIGLYOL may be used a novel oily drug-carrier.
Diacetylhematoporphyrin (diAc-Hp) . diAc-Hp accumulates in tumor tissues and responds to ultrasound. The diAc-Hp-mitomycin C conjugate enhanced the cytotoxic effect of the parent drugs under ultrasonic irradiation, indicating the aplicability of diAc-Hp as a drug-carrier. Less
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