Characteristics of Tissue Distribution of Various Polysaccharides as Drug Carriers : Influences of Molecular Weight and Anionic Charge on Tumor Targeting
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概要
- 論文の詳細を見る
Using the Walker 256 model for carcinosarcoma-bearing rats, we intravenously administered 5 polysaccharide carriers with various molecular weights (MWs) and electric charges and tested for their plasma and tissue distribution. Two carriers, carboxymethylated-D-manno-D-glucan (CMMG) and CMdextran (CMDex), showed higher plasma AUC than the other carriers tested, namely, CMchitin(CMCh), N-desulfated N-acetylated heparin(DSH), and hyaluronic acid(HA). This was consistently found to be true over the range of MWs tested. For CMDex, the maximum value of plasma AUC was obtained when the MW exceeded 150kDa. As for the anionic charge, CMDex(110-180kDa)with a degree of substitution(DS)of the CM groups ranging from 0.2 to 0.6, showed maximum plasma AUC values. Twenty-four hours after administration, the concentration of CMDex (180-250kDa ; DS : 0.6-1.2) in tumors was more than 3% of dose/g-approximately 10-fold higher than those observed with CMCh, DSH and HA. Doxorubicin(DXR) was bound to these carriers via a peptide spacer, GlyGlyPheGly(GGFG), to give carrier-GGFG-DXR conjugates (DXR content : 4.2-7.0(w/w)%), and the antitumor effects of these conjugates were tested with Walker 256 carcinosarcoma-bearing rats by monitoring the tumor weights after a single intravenous injection. Compared with free DXR, CMDex-GGFG-DXR and CMMG-GGFG-DXR conjugates significantly suppressed tumor growth, while the CMCh-GGFG-DXR, DSH-GGFG-DXR, and HA-GGFG-DXR conjugates in a similar comparison showed weak tumor growth inhibition. These findings suggest that the antitumor effect of the carrier-DXR conjugates was related to the extent with which the carriers accumulated in the tumors.
- 公益社団法人日本薬学会の論文
- 2001-05-01
著者
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矢野 喬史
Eiken Chemical Co. Ltd.
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奥野 哲
(株) ディ・ディ・エス研究所
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Yano T
Eiken Chemical Co. Ltd.
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Inoue K
Department Of Pharmacology Kobe Pharmaceutical University
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SUGAHARA Shuichi
The Second Research Department Central Technology Laboratory, Asahi Kasei Corporation
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OKUNO Satoshi
Discovery Research Laboratories, Tanabe Seiyaku Co., Ltd.
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YANO Toshiro
Discovery Research Laboratories, Tanabe Seiyaku Co., Ltd.
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HAMANA Hiroshi
Discovery Research Laboratories, Shionogi & Co., Ltd.
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INOUE Kazuhiro
Development Research Laboratories, Daiichi Pharmaceutical Co., Ltd.
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Yano T
Discovery Research Laboratories Tanabe Seiyaku Co. Ltd.
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矢野 敏朗
Drug Delivery System Institute Ltd. :(present Address)tanabe Seiyaku Co. Ltd.
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Yano Toshiro
Drug Delivery System Institute Ltd.
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Okuno S
Discovery Research Laboratories Tanabe Seiyaku Co. Ltd.
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Hamana H
Shionogi Research Laboratories Shionogi & Co. Ltd.
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Hamana H
Discovery Research Laboratories Shionogi & Co. Ltd.
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Sugahara Shuichi
The Second Research Department Of Central Technology Laboratory Asahi Kasei Corporation
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Inoue Kazuhiro
Pharmaceutical Dev. Laboratories Sankyo Co. Ltd.
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Hamana Hiroshi
Dep. Of Pharmaceutical Chemistry Chiba Inst. Of Sci.
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