Pharmacokinetics and targeted delivery of proteins and genes

Mitsuru Hashida, Ram I. Mahato, Kenji Kawabata, Takenori Miyao, Makiya Nishikawa, Yoshinobu Takakura

Research output: Contribution to journalArticle

49 Scopus citations

Abstract

The effectiveness of various approaches for controlling in vivo disposition of proteins and genes was compared based on pharmacokinetic analysis. The potential of introduction of galactose or mannose residues aiming at receptor-mediated endocytosis, succinylation to be recognized by a scavenger receptor, and cationization for universal electrostatic interaction were characterized using model proteins. Corresponding to the results, a superior therapeutic effect was shown with derivatives of superoxide dismutase against hepatic and renal ischemia/reperfusion injury. A similar approach was adopted for plasmid DNA and oligonucleotide and their rapid degradation in the blood pool and preferential uptake by the liver after intravenous injection were characterized by pharmacokinetic analysis. The effects of incorporation into cationic liposomes and conjugation with macromolecules on their in vivo distribution were also elucidated.

Original languageEnglish (US)
Pages (from-to)91-97
Number of pages7
JournalJournal of Controlled Release
Volume41
Issue number1-2
DOIs
StatePublished - Aug 1996

Keywords

  • Cationic liposomes
  • Chemical modification
  • Pharmacokinetics
  • Protein and gene targeting
  • Receptor-mediated endocytosis

ASJC Scopus subject areas

  • Pharmaceutical Science

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