高等学校化学学报

高等学校化学学报

• 研究论文 • 上一篇    下一篇

甲氨喋呤-乳糖酰基壳聚糖的制备及其体外实验

王银松1, 韩月莲2, 李英霞3, 王玉玫1, 李荣珊1   

    1. 天津医科大学药学院, 天津 300070;
    2. 青岛海尔药业有限公司, 青岛 266103;
    3. 中国海洋大学海洋药物与食品研究所, 青岛 266003
  • 收稿日期:2006-10-16 修回日期:1900-01-01 出版日期:2007-06-10 发布日期:2007-06-10
  • 通讯作者: 王银松

Preparation and in vitro Experimental Study of Methotrexate-Lactosyl-Chitosan Conjugate

WANG Yin-Song1*, HAN Yue-Lian2, LI Ying-Xia3, WANG Yu-Mei1, LI Rong-Shan1   

    1. Pharmacy College, Tianjin Medical University, Tianjin 300070, China;
    2. Qingdao Hair Pharmaceutical Co. Ltd., Qingdao 266103, China;
    3. Institute of Marine Drug and Food, Ocean University of China, Qingdao 266003, China
  • Received:2006-10-16 Revised:1900-01-01 Online:2007-06-10 Published:2007-06-10
  • Contact: WANG Yin-Song

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被引次数

45

摘要： 制备了不同乳糖酰基取代度的N-乳糖酰基壳聚糖(LCH), 并通过红外光谱(IR)及核磁共振氢谱(1H NMR)对其进行了结构表征. 体外放射性配基竞争结合实验结果显示, 当乳糖酰基取代度为15.5%~38.9%时, LCH对肝实质细胞膜表面去唾液酸糖蛋白受体(ASGPR)具有特异亲和性, 即具有潜在的肝靶向性. 将甲氨喋呤(MTX)与壳聚糖以酰胺键偶联, 制备MTX-壳聚糖(MTX-CH), 再与乳糖酸反应生成目标产物MTX-乳糖酰基壳聚糖(MTX-LCH), 并通过紫外分光光度法(UV)检测MTX的取代度为5.6%, 乳糖酰基取代度为33.8%. 溶解性实验结果显示, MTX-LCH溶于pH=1~14的水溶液; 体外释放实验结果表明, MTX-LCH性质稳定, 能明显延缓MTX的释放.

关键词: N-乳糖酰基壳聚糖, 甲氨喋呤, 去唾液酸糖蛋白受体, 肝靶向, 高分子前体药

Abstract: N-Lactosyl-chitosan(LCH) with different degrees of substitution(DS) of lactosyl group was synthesized and characterized with Fourier transform infrared(FTIR) and proton nuclear magnetic resonance(1H NMR). The result of radioactive experiment in vitro shows that LCH was a specific ligand for asialoglycoprotein receptor(ASGPR) when the DS of lactosyl group ranged from 15.5% to 38.9%, which indicates LCH could be used as a novel kind of hepatic targeting carrier. Methotrexate-lactosyl-chitosan(MTX-LCH) was prepared via the following synthetic route: MTX was firstly coupled with chitosan, and then reacted with lactobionic acid to produce MTX-LCH. The DS of MTX moiety of MTX-LCH was determined via ultraviolet(UV) spectroscopy to be 5.6%, and the DS of lactosyl group to be 33.8%. MTX-LCH was water-soluble in the pH range of 1—14. The dynamic dialysis study shows that MTX-LCH was stable, and the release of MTX was very slow. These results provided a reference for the further study of liver-targeting polymeric prodrugs.

Key words: N-Lactosyl chitosan, Methotrexate, Asialoglycoprotein receptor, Liver-targeting, Polymeric prodrug

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