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Establishment of Evaluation Method for Function of Drug Targeting Systems and Systematization of their Physicochemical Character-Function Relationship

Research Project

Project/Area Number 05452338
Research Category

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

Allocation TypeSingle-year Grants
Research Field Physical pharmacy
Research InstitutionKYOTO UNIVERSITY

Principal Investigator

HASHIDA Mitsuru  KYOTO UNIVERSITY FAC.PHARM.SCI.PROFESSOR, 薬学部, 教授 (20135594)

Co-Investigator(Kenkyū-buntansha) TAKAKURA Yoshinobu  KYOTO UNIVERSITY FAC.PHARM.SCI.ASSOCIATE PROFESSOR, 薬学部, 助教授 (30171432)
Project Period (FY) 1993 – 1994
Project Status Completed (Fiscal Year 1994)
Budget Amount *help
¥7,100,000 (Direct Cost: ¥7,100,000)
Fiscal Year 1994: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 1993: ¥5,500,000 (Direct Cost: ¥5,500,000)
KeywordsDrug delivery system / Targeting / Macromolecular carrier system / Micropaticulate carrier system / Organ clearance / Organ perfusion experiment / Cultured cells / 製剤特性 / ドラッグデリバリーシステム
Research Abstract

Recently, drug targeting approaches have attracted great interest for optimization of drug delivery. The use of drug carriers is one of the most promising ways to accomplish the drug targeting. Great efforts have been made to develop carrier systems, however, most approaches are done through trial and error or based on only experiences. The purposes of this tesearch project were as follows. First, to establish the evaluation method for targeting systems. Second, to systematize the pharmacokinetic characteristics of drug carriers. Third, to establish the methodology for drug targeting. In order to study at whole body, organ, and cellular levels, in vivo distribution experiments, organ perfusion experiments, and in vitro experiments using cultured cells were carried out. Through these experiments, we have clarified the relationship between the pharmacokinetic characteristics of macromolecular and microparticulate carriers and their physicochemical properties, such as size and charge. Based on the findings, we have developed some targeting delivery systems of superoxide dismutase (antioxidant enzyme) and vitamin K5 (blood coagulant).

Report

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

    (59 results)

All Other

All Publications (59 results)

  • [Publications] Takino,T.: "Long circulating emulsion carrier systems for highly lipophilic drugs." Biol.Pharm.Bull.17. 121-125 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Hashida,M.: "Targeting delivery of protein drugs by chemical modification." Drug Dev.Ind.Pharm.20. 581-590 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Mihara,K.: "Manipulation of renal disposition of human recombinant superoxide dismutase by chemical modification" Biol.Pharm.Bull.17. 296-301 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Takakura,Y.: "Targeted delivery of superoxide dismutase to macrophages via Mannose receptor-Mediated mechanism." Biochem.Pharmacol.47. 853-858 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Takakura,Y.: "Control of the disposition profiles of proteins in the kidney via chemical modification." J.Controlled Release. 28. 111-119 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Takakura,Y.: "Pharmacokinetics of succinylated proteins and dextran sulfate in mice:Imblications for hepatic targeting of protein drugs by direct succinylation via scavenger receptors." Int.J.Pharmaceut.105. 19-29 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Fujita,T.: "Control of in vivo fate of albumin deriatives utilizing combined chemical modification." J.Controlled Release. 2. 157-165 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Hashida,M.: "Pharmacokinetics in design of polymeric drug delivery systems." J.Controlled Release. 31. 163-171 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Mihara,K.: "Improvement of therapeutic effect of human recombinant superoxide dismutase on ischemic acute renal failute in the rat via cationization and conjugation with polyethylene glycol." J.Drug Targeting. 2. 317-321 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Takino,T.: "Pharmacokinetic disposition analysis of lipophilic drugs ingected with various lipid carriers in the single-pass rat liver perfusion system." Int.J.Pharmaceut.114. 43-54 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Nishikawa,M.: "Design for cell-specific targeting of proteins utilizing suger-recognition mechanism:Effect of molecular weight of proteins on targeting efficiency." Pharm.Res.12. 217-222 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Nishikawa,M.: "Galactosylated proteins are recognized by the liver according to the surface density of galactose moieties." Am.J.Physiol.(in press). (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Toichi Takino: "Long circulating emulsion carrier systems for highly lipophilic drugs19GC01 : Biol.Pharm.Bull." 17. 1-125 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Mitsuru Hashida: "Targeting delivery of protein drugs by chemical modification" Drug Dev.Ind.Pharm.20. 581-590 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Kiyoshi Mihara: "Manipulation of renal disposition of human recombinant superoxide dismutase by chemical modification" Biol.Pharm.Bull.17. 296-301 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Yoshinobu Takakura: "Targteted delivery of superoxide dismutase to macrophages via mannose receptor-mediated mechanism" Biochem.Pharmacol.47. 853-858 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Yoshinobu Takakura: "Control of the disposition profiles of proteins in the kidney via chemical modification" J.Controlled Release. 28. 111-119 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Yoshinobu Takakura: "Pharmacokinetics of succinylated proteins and dextran sulfate in mice : Implications for hepatic targeting of protein drugs by direct succinylation via scavenger receptors" Int.J.Pharmaceut. 105. 19-29 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Takuya Fujita: "Control of in vivo fate of albumin derivatives utilizing combined chemical modification" J.Drug Targeting. 2. 157-165 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Mitsuru Hashida: "Pharmacokinetics in design of polymeric drug delivery systems" J.Controlled Release. 31. 163-171 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Kiyoshi Mihara: "Improvement of therapeutic effect of human recombinant superoxide dismutase on ischemic acute renal failure in the rat via cationization and conjugation with polyethylene glycol" J.Drug Targeting. 2. 317-321 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Toichi Takino: "Pharmacokinetic disposition analysis of lipophilic drugs injected with various lipid carriers in the single-pass rat liver perfusion system" Int.J.Pharmaceut.114. 43-54 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Makiya Nishikawa: "Design for cellspecific targeting of proteins utilizing sugar-recognition mechanism : Effect of molecular weight of proteins on targeting efficiency" Pharm.Res.12. 217-222 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Makiya Nishikawa: "Galactosylated proteins are recognized by the liver according to the surface density of galactose moieties" Am.J.Physiol.(in press). (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Takino,T.: "Long circulating emulsion carrier systems for highly lipophilic drugs." Biol.Pharm.Bull.17. 121-125 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Hashida,M.: "Targeting delivery of protein drugs by chemical modification." Drug Dev.Ind.Pharm.20. 581-590 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Mihara,K.: "Manipulation of renal disposition of human recombinant superoxide dismutase by chemical modification." Biol.Pharm.Bull.17. 296-301 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Takakura,Y.: "Targeted delivery of superoxide dismutase to macrophages via Mannose receptor-Mediated mechanism." Biochem.Pharmacol.47. 853-858 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Takakura,Y.: "Control of the disposition profiles of proteins in the kidney via chemical modification." J.Controlled Release.28. 111-119 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Takakura,Y.: "Pharmacokinetics of succinylated proteins and dextran sulfate in mice:Implications for hebatic targeting of protein drugs by direct succinylation via scavenger receptors." Int.J.Pharmaceut.105. 19-29 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Fujita,T.: "Control of in vivo fate of albumin derivatives utilizing combined chemical modification." J.Controlled Release. 2. 157-165 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Hashida,M.: "Pharmacokinetics in design of polymeric drug delivery systems." J.Controlled Release. 31. 163-171 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Mihara,K.: "Improvement of therapeutic effect of human recombinant superoxide dismutase on ischemic acute renal failute in the rat via cationization and conjugation with polyethylene glycol." J.Drug Targeting. 2. 317-321 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Takino,T.: "Pharmacokinetic disposition analysis of lipophilic drugs ingected with various lipid carriers in the single-pass rat liver perfusion system." Int.J.Pharmaceut.114. 43-54 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Nishikawa,M: "Design for cell-specific targeting of proteins utilizing suger-recognition mechanism:Effect of molecular weight of proteins on targeting efficiency." Pharm.Res.12. 217-222 (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] Nishikawa,M: "Galactosylated proteins are recognized by the liver according to the surface density of galactose moieties." Am.J.Physiol.(in press). (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] Nishikawa,M.: "Synthesis and pharmacokinetics of a new liver-specific carrier,glycosylated carboxymethyl-dextran,and its application to drug targeting" Pharm.Res.10. 1253-1264 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Tokuda,H.: "Specific uptake of succinylated proteins via a scavenger receptor-mediated mechanism in cultured brain microvessel endothelial cells" Biochem.Biophys.Res.Commun.196. 18-24 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Takino,T.: "Controlled biodistribution of highly lipophilic drugs with various parenteral" J.Drug Targeting. 1. 117-124 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Mihara,K.: "Disposition characteristics of protein drugs in the perfused rat kidney" Pharm.Res.10. 823-827 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Hashida,M.: "Targeting Delivery of protein drugs by chemical modification" Drug Dev.Ind.Pharm.20. 581-590 (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] Takino,T.: "Long circulating emulsion carrier systems for highly lipophilic drugs" Biol.Pharm.Bull.17. 121-125 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Ohe,Y.: "Combination effect of vaccination with IL2 and IL4 cDNA transfected cells on the induction of a therapeutic immune response against lewis lung carcinoma cells" Int.J.Cancer. 53. 432-437 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Nishio,M.: "Pharmacokinetic re-evaluation and phase I study of high dose epirubicin in advanced non-small cell lung cancer" Jpn.J.Clin,.Oncol.23. 284-290 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Karato,A.: "Phase I study of CPT-11 and etoposide in patients with refractory solid tumors" J.Clin.Oncol.11. 2030-2035 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Sato,K.: "Granulocyte colony-stimulating factor produced by bladder carcinoma of a patient with leukemoid reaction did not affect proliferation of the tumor cells" J.Urol.(in press).

    • Related Report
      1993 Annual Research Report
  • [Publications] Tanigawa,N.: "Thymidine uptake in vitro as a prognostic indicator for primary gastric cancer" Cancer. 72. 2883-2888 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Tanigawa,N.: "Detection of P-glycoprotein in solid tumors by flow cytometry" Anti-cancer Res.13. 2171-2176 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Tashiro,T.: "Mechanisms for reduced drug accumulation in cisplatin-resistant sublines of human small cell lung cancer cell lines" KURRI Prog.Rep.1992. 270-271 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Naito,M.: "Enhancement of cellular accumulation of cyclosporine by anti-P-glycoprotein monoclonal antibody MRK-16 and synergistic modulation of multidrug resistance" J.Natl.Cancer Inst.85. 311-316 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Naito,M.: "Enhancement of reversing effect of cyclosporin A on vincristine resistance by anti-P-glycoprotein monoclonal antibody MRK-16" Jpn.J.Cancer Res.84. 489-492 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Noguchi,K.: "cDNA expression cloning of the 85-kDa protein overexpressed in adriamycin-resistant cells" Biochem.Biophys.Res.Commun.192. 88-95 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Satoh,M.: "Modulation of both cisplatin nephrotoxicity and drug resistance in murine bladder tumor by controlling metallothionein synthesis" Cancer.Res.53. 1829-1832 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Kondo,Y.: "Tissue-specific induction of metallothionein by bismuth as a promising protocol for chemotherapy with repeated administration of cis-diamminedichloroplatinum(II)against bladder tumor" Anticancer Res.12. 2303-2308 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Satoh,M.: "Prevention of carcinogenicity of anticancer drugs by metallothionein induction" Cancer Res.53. 4767-4768 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Sugimoto,Y.: "Molecular cloning and characterization of the complementary DNA for the Mr 85,000 Protein overexpressed in Adriamycin-resistant human tumor cells" Cancer Res.53. 2538-2543 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Dranoff,G.: "Vaccination with irradiated tumor cells engineered to secrete murine granulocyte-macrophage colony-stimulating factor stimulates potent,specific,and long-lasting anti-tumor immunity" Proc.Natl.Acad.Sci.USA. 90. 3539-3543 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Hashida,M.: "Drug targeting with macromolecular carrier systems.in"Perspectives in Medicinal Chemistry"(Eds.Testa,B,et al.)pp.545-558" Verlag Helvestica Chimica Acta,Basel, 644 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Hanada,H.: "Strategies for immunogene therapy against cancer.in"Excerpta Medical International Congress Series"" Excerpta Medica,Tokyo, in press (1994)

    • Related Report
      1993 Annual Research Report

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Published: 1993-04-01   Modified: 2016-04-21  

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