Saccharide-branched Cyclodextrins as Targeting Drug Carriers |
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Authors: | Kenjiro Hattori Akira Kenmoku Tsukasa Mizuguchi Daisuke Ikeda Mamoru Mizuno Toshiyuki Inazu |
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Institution: | (1) Department of Nanochemistry, Faculty of Engineering, Tokyo Polytechnic University, 243-0297 Atsugi, Kanagawa, Japan;(2) The Noguchi Institute, 173-0003 Tokyo, Itabashi, Japan;(3) Department of Applied Chemistry, Faculty of Engineering, Tokai University, 259-1292 Hiratsuka, Kanagawa, Japan |
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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. |
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Keywords: | cyclodextrin doxorubicin liver cell oligosaccharide PNA lectin SPR targeting drug delivery system |
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