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Development of local drug disposition analysis and delivery methods in human solid tumors

Research Project

Project/Area Number 12557212
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Biological pharmacy
Research InstitutionKYOTO UNIVERSITY

Principal Investigator

TAKAKURA Yoshinobu  Kyoto University, Grad. Sch. Pharm. Sci., Professor, 薬学研究科, 教授 (30171432)

Co-Investigator(Kenkyū-buntansha) YAMASHITA Fumiyoshi  Kyoto University, Grad. Sch. Pharm. Sci., Associate Professor, 薬学研究科, 助教授 (30243041)
YAMAOKA Kiyoshi  Kyoto University, Grad. Sch. Pharm. Sci., Associate Professor, 薬学研究科, 助教授 (50109013)
Project Period (FY) 2000 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥10,100,000 (Direct Cost: ¥10,100,000)
Fiscal Year 2001: ¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 2000: ¥7,600,000 (Direct Cost: ¥7,600,000)
Keywordssolid tumors / drug delivery system / local administration / gene therapy / antisense oligonucleotide / plasmid DNA / ヒト腫瘍細胞 / 単離腫瘍灌流実験系
Research Abstract

To construct a strategy for developing efficient and safe in vivo drug delivery systems to solid tumors, a series of pharmacokinetic studies following local administration were carried out. The intratumoral pharmacokinetics of a second-generation antisense oligonucleotid were studied in rat Walker 256 tissue-isolated tumor preparations using an in situ single-pass vascular perfusion technique. Some first-generation oligonucleotides were also used for comparison. These oligonucleotides were administrated directly into the tumor in two ways : constant arterial infusion and direct intratumoral injection. The results suggested that the oligonucleotide may be useful for direct local injection into solid tumors. On the other hand, the intratumoral pharmacokinetics of naked plasmid DNA and gene expression were examined in mice bearing solid tumors. Plasmid DNA was rapidly eliminated from the injection site and lymphatic transfer was observed. Intratumoral injection of naked naked plasmid DNA encoding the luciferase gene into subcutaneously inoculated mouse colon tumor resulted in significant gene expression. The gene expression was inhibited when defined polyanions were injected simultaneously, implying the involvement of a specific mechanism in cellular uptake of plasmid DNA These results demonstrated that tumor tissue might be a promising target for direct gene transfer.with naked plasmid DNA. Thus, the present study provides useful information about the basic disposition characteristics of gene drugs, such as antisense oligonucleotides and plasmid DNA in solid tumors.

Report

(3 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • Research Products

    (2 results)

All Other

All Publications (2 results)

  • [Publications] Yoshinobu Takakura: "Development of gene drug delivery systems based on pharmacokinetic studies"European Journal of Pharmaceutical Sciences. 13. 71-76 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yoshinobu Takakura: "Development of gene drug delivery systems based on pharmacokinetic studies"European Journal of Phamaceutical Sciences. 13. 71-76 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary

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Published: 2000-04-01   Modified: 2016-04-21  

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