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1994 Fiscal Year Final Research Report Summary

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
KeywordsDrug delivery system / Targeting / Macromolecular carrier system / Micropaticulate carrier system / Organ clearance / Organ perfusion experiment / Cultured cells
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).

  • Research Products

    (24 results)

All Other

All Publications (24 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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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

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Published: 1996-04-15  

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