用于塞来昔布结肠定位递释的葡聚糖载体大分子
Dextran carrier macromolecule for colon specific delivery of celecoxib.
机构信息
Department of Pharmaceutics, Institute of Technology, Banaras Hindu University, Varanasi, U.P., India.
出版信息
Curr Drug Deliv. 2010 Apr;7(2):144-51. doi: 10.2174/156720110791011828.
The colon specific polymeric conjugates of celecoxib were prepared with dextran of different molecular weight Mr approximately 40 000, 70 000, and 100 000 (CSD-40, CSD-70 and CSD-100). Succinic acid was used as linker between the drug and dextran. The prepared conjugates were characterized by UV, IR, 1H NMR and HPLC. The maximum degree of substitution 3.9+/-0.20 % was found with the dextran CSD-100 conjugates. The percent release of drug obtained by in-vitro hydrolysis studies, was found to be 24.37+/- 0.6, 23.0 +/- 0.5 and 20.13+/- 0.8 in simulated colonic fluid (SCF) pH 6.8 while 17.90 +/- 0.4, 16.8+/- 0.75 and 15.47 +/- 0.5 in simulated intestinal fluid (SIF) pH 7.4 for CSD-40, CSD-70 and CSD-100, respectively, in both medium. The drug release from the conjugates was observed for 24 h in 3% w/v rat caecal content and found to be 41.77 +/- 1.2, 39.03 +/- 1.0 and 35.26 +/- 1.09 for CSD-40, CSD-70 and CSD-100 conjugates, respectively. The half life of conjugates was determined and was found to be short in 3% w/v rat caecal content. No amount of drug was released in simulated gastric fluid pH 1.2 and stomach homogenate in 2 h. The amount of drug released from small intestine homogenate was 3.4+/- 0.1 percent in 12 h for the CSD-40. The above result suggests that dextran could be used as a macromolecular carrier for colon specific drug delivery of celecoxib.
采用不同相对分子质量（Mr 约 40000、70000 和 100000）的葡聚糖（CSD-40、CSD-70 和 CSD-100）制备塞来昔布的结肠定位聚合偶联物。采用丁二酸作为药物和葡聚糖之间的连接物。通过 UV、IR、1H NMR 和 HPLC 对制备的偶联物进行了表征。CSD-100 偶联物的最大取代度为 3.9±0.20%。体外水解研究表明，在模拟结肠液（SCF）pH6.8 中，CSD-40、CSD-70 和 CSD-100 的药物累积释放率分别为 24.37±0.6%、23.0±0.5%和 20.13±0.8%，而在模拟肠液（SIF）pH7.4 中分别为 17.90±0.4%、16.8±0.75%和 15.47±0.5%。在 3%w/v 大鼠盲肠内容物中，观察到偶联物在 24 h 内的药物释放，CSD-40、CSD-70 和 CSD-100 的药物累积释放率分别为 41.77±1.2%、39.03±1.0%和 35.26±1.09%。测定了偶联物的半衰期，发现其在 3%w/v 大鼠盲肠内容物中半衰期较短。在 pH1.2 的模拟胃液和 2 h 的胃匀浆中均未释放药物。在 12 h 内，CSD-40 从小肠匀浆中释放的药物量为 3.4±0.1%。以上结果表明，葡聚糖可用作塞来昔布结肠定位给药的高分子载体。
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