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Development of Novel Anticancer Drug-Carriers Targetable to Tumor Blood Vessels.

Research Project

Project/Area Number 04557072
Research Category

Grant-in-Aid for Developmental Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field Urology
Research InstitutionAkita University

Principal Investigator

KATO Tetsuro  Akita University, School of Medicine, Associate Professor, 医学部, 助教授 (40004642)

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)
新藤 雅彰  秋田大学, 医学部, 講師 (00108929)
海野 勝男  秋田大学, 医学部, 教授 (40111322)
Project Period (FY) 1992 – 1994
Project Status Completed (Fiscal Year 1994)
Budget Amount *help
¥15,500,000 (Direct Cost: ¥15,500,000)
Fiscal Year 1994: ¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 1993: ¥3,900,000 (Direct Cost: ¥3,900,000)
Fiscal Year 1992: ¥8,900,000 (Direct Cost: ¥8,900,000)
KeywordsAnticancer drug / Carrier / Tumor vessels / Ethylcellulose / Polylactic acid / Triglyceride / Hematoporphyrin / 腫瘍栄養動脈 / マイクロカプセル / エマルジョン / 抗がん剤 / 撰択的化学療法
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

Report

(4 results)
  • 1994 Annual Research Report   Final Research Report Summary
  • 1993 Annual Research Report
  • 1992 Annual Research Report
  • Research Products

    (33 results)

All Other

All Publications (33 results)

  • [Publications] Kato T, Sato K, Kakinuma H, Matsuda Y: "Enhanced suppression of tumor growth by combination of angiogenesis inhibitor TNP-470 and cytotoxic agents in mice." Cancer Research. 54. 5143-5147 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Okada H, Doken Y, Orawa Y, Toguchi H: "Preparation of three-month depot injectable microspheres of leuprorelin acetate using biodegradable polymers." Pharmaceutical Research. 11. 1143-1147 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Okada H, Yamamoto M, Heya T, et al: "Drug delivery using biodegradable microspheres." Journal of Controlled Release. 28. 221-229 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Yanai S, Okada H, Misaki M, et al: "Antitumor activity of a medium-chain triglyceride solution of the angiogenesis inhibitor TNP-470 when administered via the hepatic artery to rats." Journal of Pharmacology and Experimental Therapeutics. 271. 1267-1273 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Suzuki T, Kamada S, Yoshida Y, Unno K: "A study on sonodynamic therapy -antitumor effect of novel sonodynamic compounds under ultrasound." Heterocycles. 38. 1209-1211 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 柿沼秀秋、佐藤一成、三浦邦夫、他: "前立腺癌ならびに腎癌の骨転移に対するマイトマイシンCマイクロカプセル化学塞栓療法の検討" 日本泌尿器科学会雑誌. 58. 1116-1123 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Kato T: "Microspheres and Regional Cancer Therapy (ed. N. Willmott)" CRC Press, Boca Raton, FL, USA, 2 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Kato T: "Urological Oncology (ed. J. Waxman)" Edward Arnold, London, 15 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Kato T,Sato K,Kakinuma H,Matsuda Y :"Enhanced suppression of tumor growth by combination of angiogenesis inhibitor TNP-470 and cytotoxic agents in mice." Cancer Research. 54. 5143-5147 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Kato T :"Foreword." Microspheres and Regional Cancer Therapy, edited by N.Willmott, pp 1-2, CRC Press, Boca Raton, FL,USA. (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Okada H,Doken Y,Ogawa Y,Toguchi H :"Preparation of three-month depot injectable microspheres of leuprorelin acetate using biodegradable polymers." Pharmaceutical Research, 11 : 1199-1203,1994.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Okada H,Yamamoto M,Heya T,et al :"Drug delivery using biodegradable microspheres." Journal of Controlled Release. 28. 221-229 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Yanai S,Okada H,Misaki M,et al :"Antitumor activity of a medium-chain triglyceride solution of the angiogenesis inihibitor TNP-470 when administered via the hepatic artery to rats." Journal of Pharmacology and Experimental Therapeutics. 271. 1267-1273 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Suzuki T,Kamada S,Yoshida Y,Unno K :"A Study on sonodynamic therapy-antitumor effect of novel sonodynamic compounds under ultrasound." Heterocycles. 38. 1209-1211 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Sato K,Kato T :"Cancer chemotherapy targeted to tumor vessels." Japanese Jouranl of Cancer Chemotherapy. 21. 295-300 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Kakinuma H,Sato K,Miura K,Sasaki S,Kato T :"Effect of mictomycin C microcapsule chemoembolization on bone metastases of prostatic and renal cancer." Japanese Journal of Urology. 56. 1116-1123 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Kato T :"Renal cell carcinoma." Arterial Infusion Chemotherapy, 2nd edition, edited by Taguchi T,Nakamura M,pp 463-474, Gan-to-Kagakuryouhousha, Tokyo. (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Kato T :"Prostate Cancer." Arterial Infusion Chemotherapy, 2nd edition, edited by Taguchi T,Nakamura M,pp 475-482, Gan-to-Kagakuryouhousha, Tokyo. (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Kamei S,Okada H,Inoue Y,et al :"Antitumor effects of angiogenesis inhibitor TNP-470 in rabbits bearing VX2-2 carcinoma by arterial administration of microspheres and oil emulsion." Journal of Pharmacology and Experimental Therapy. 264. 469-474 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Kato T. :"Embolization of the kidney." Urological Oncology, edited by J.Waxman, pp 216-230, Edward Arnold, London. (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Kato,T.et al.: "Enhanced suppression of tumor growth by combination of angiogenesis inhibitor TNP-470 and cutotoxic agents in mice." Cancer Research. 54. 5143-5147 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Okada,H.et al.: "Preparation of three-month depot injectable microspheres of leuprorelin acetate using biodegradable polymers." Pharmaceutical Research. 11. 1143-1147 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Okada,H.et al.: "Drug delivery using biodegradable microspheres." Journal of Controlled Release. 28. 221-229 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 佐藤 一成,他: "腫瘍血管を標的としたがん治療" 癌と化学療法. 21. 295-300 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 柿沼 秀秋,他: "前立腺癌ならびに腎癌の骨転移に対するマイトマイシンCマイクロカプセル化学塞栓療法の検討" 日本泌尿器科学会雑誌. 58. 1116-1123 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Kato,T.: "Microspheres and Regional Cancer Therapy(ed.N.Willmott)" CRC Press,Boca Raton,FL,USA, 2 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Kato,T.: "Urological Oncology(ed.J.Waxman)" Edward Arnold,London, 15 (1992)

    • Related Report
      1994 Annual Research Report
  • [Publications] 加藤哲郎・他2名: "DDSを応用した癌治療の進歩「腎癌」" 外科治療. 69. 168-173 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Kamei,S.et al: "Antitumor effects of angiogenesis inhibitor TNP-470 in rabbits VX2 carcinoma by arterial admin.of microspheres and oil." J.Pharmacol.Exp.Therapeut.264. 469-474 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Kato,T.: "Embolization of the kidney.In:Urological Oncology(ed.Waxman J & Williams,G)" Urological Oncology,Edward Arnold,London. 216-230 (1992)

    • Related Report
      1993 Annual Research Report
  • [Publications] Kato,T.et al: "Enhanced suppression of tumor growth by combination of angiogenesis inhibitor TNP-470 and cytotoxic agents." Cancer Res.(in press). (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] Kato,T.: "Embolization of the kidney." Urological Oncology(Waxman J & Williams G,ed)Edward Arnold,London. 216-230 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] 加藤 哲郎ほか: "血管新生阻害剤と抗癌剤の併用効果に関する基礎的研究" 第51回日本癌学会総会記事. 395- (1992)

    • Related Report
      1992 Annual Research Report

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Published: 1992-04-01   Modified: 2016-04-21  

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