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Enhanced Accumulation of Sialyl Lewis X-Carboxymethylpullulan Conjugate in Acute Inflammatory Lesion

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Abstract

Purpose. E-selectin is a cell adhesion molecule that is specifically expressed in the inflammatory vascular endothelium in response to cytokines such as IL-1β and TNF-α, and interacts with specific ligands containing sialyl Lewis X (Neu5Acα2-3Galβl-4(Fucαl-3)GlcNAc-, SLex). In order to investigate the ability of E-selectin ligands to target the inflammatory site, the tissue distribution of carboxymethylpullulan (CMPul) modified with SLex was studied.

Methods. CMPul conjugates with various saccharides containing SLex and monovalent SLex were intravenously administered to mice with ear edema induced by arachidonic acid, and their distributions to the inflamed ear and other tissues were studied. To determine the microdistributions of these compounds, the inflamed ear was subjected to microautoradiography.

Results. After intravenous administration AUC0-24h of SLex-CMPul, which binds to E-selectin, in the inflamed ear was about 300-fold and 2.5-fold higher than that of monovalent SLex and CMPul conjugated with other saccharides, which can not serve as ligands for E-selectin. Microautoradiography also revealed SLex-CMPul accumulated at the microvessels in the inflammatory lesions.

Conclusions. SLex-CMPul was found to have the potential to target drugs to the inflammatory lesion.

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Authors and Affiliations

  1. Drug Delivery System Institute, Ltd., 2669 Yamazaki, Noda-shi, Chiba, 278, Japan

    Kazutoshi Horie, Masahiro Sakagami, Kentaro Kuramochi, Hiroshi Hamana & Teruomi Ito

  2. Discovery Research Laboratories, Shionogi & Co., Ltd., 5-12-4, Sagisu, Fukushima-ku, Osaka, 553-0002, Japan

    Masahiro Sakagami, Kohji Hanasaki & Hiroshi Hamana

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  1. Kazutoshi Horie
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  2. Masahiro Sakagami
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  3. Kentaro Kuramochi
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  5. Hiroshi Hamana
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Correspondence to Kazutoshi Horie.

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Horie, K., Sakagami, M., Kuramochi, K. et al. Enhanced Accumulation of Sialyl Lewis X-Carboxymethylpullulan Conjugate in Acute Inflammatory Lesion. Pharm Res 16, 314–320 (1999). https://doi.org/10.1023/A:1018849029727

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