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Saccharide-branched Cyclodextrins as Targeting Drug Carriers

  • Kenjiro Hattori
  • Akira Kenmoku
  • Tsukasa Mizuguchi
  • Daisuke Ikeda
  • Mamoru Mizuno
  • Toshiyuki Inazu
Article

Abstract

A synthetic series of heptakis-galactose-branched cyclodextrins (termed CDs) having a longer spacer arm using two amino-caproic acids as an enlarging unit were prepared. Starting with heptakis-amino-β-CD or heptakis-amino-caproic-amide-β-CD, treated with galactosyl-glucono-amide-caproic acid, the new compounds heptakis (Gal-cap1)-CD (4) or heptakis (Gal-cap2)-CD (5) were obtained. The longer galactose spacer arm extremely favors the PNA association. The effect of branch length on K with PNA was enhanced up to 138-fold 3 as well as with DXR enhanced up to 81-fold. Hexakis (Gal-cap2)-CD (6) was prepared and the association constants with rat liver cells were observed to be 2.5 × 1010 M−1. A multi-high mannose type oligosaccharide branched CD (7) showed a large association constant with DXR up to 1.1 × 109 M−1. The two-dimensional map for the association constants of newly synthesized oligosaccharide-branched CDs toward lectin or liver cells versus the association constants toward a drug (doxorubicin) suggested a method of finding a better targeting drug carrier. The structural effect of the oligosaccharide-CDs showed that the number and length of the branch were dominant factors in designing for enhanced dual recognition.

Keywords

cyclodextrin doxorubicin liver cell oligosaccharide PNA lectin SPR targeting drug delivery system 

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Copyright information

© Springer 2006

Authors and Affiliations

  • Kenjiro Hattori
    • 1
  • Akira Kenmoku
    • 1
  • Tsukasa Mizuguchi
    • 1
  • Daisuke Ikeda
    • 1
  • Mamoru Mizuno
    • 2
  • Toshiyuki Inazu
    • 3
  1. 1.Department of Nanochemistry, Faculty of EngineeringTokyo Polytechnic UniversityAtsugiJapan
  2. 2.The Noguchi InstituteTokyoJapan
  3. 3.Department of Applied Chemistry, Faculty of EngineeringTokai UniversityHiratsukaJapan

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