Synthesis of sialyl Lewis X-polysaccharide conjugates.
Sialyl Lewis X (SLeX) is well known as a ligand of the cell adhesion molecule E-selectin which is specifically expressed at inflammatory lesion sites. We have synthesized several SLeX-polysaccharide conjugates and examined their potential for drug delivery to inflammatory lesions. The AUC (area under the blood concentration-time curve) 0-24 h of SLeX-CMCht (1), SLeX-CMPul (2) and SLeX-DSH (3) at the inflammatory lesion was about 60-, 300-, and 30-fold higher than that of the monovalent SLeX (7), respectively. Moreover, 1 showed 2-fold higher accumulation in the inflammatory lesion than SLN-CMCht (4), and 2 showed 2.5-fold higher accumulation than SLN-CMPul (5).
Sakagami
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M
Drug Delivery System Institute, Ltd., Noda, Chiba, Japan. masahiro.sakagami@shionogi.co.jp
Horie
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Nakamoto
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Kawaguchi
T
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Hamana
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D000818:Animals; D019540:Area Under Curve; D002240:Carbohydrate Sequence; D016503:Drug Delivery Systems; D004487:Edema / Q000139:chemically induced / Q000473:pathology; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008969:Molecular Sequence Data; D009844:Oligosaccharides / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D011134:Polysaccharides / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D000080506:Sialyl Lewis X Antigen
D009844:Oligosaccharides; D011134:Polysaccharides; D000080506:Sialyl Lewis X Antigen