Dendrimers conjugates for colonic delivery of 5-aminosalicylic acid
Dendrimers conjugates for colonic delivery of 5-aminosalicylic acid
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DOI：
10.1016/s0168-3659(02)00461-3
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发表时间：
2003-02-14
影响因子：
10.8
通讯作者：
Saramunee, K
中科院分区：
文献类型：
--
作者：
Wiwattanapatapee, R;Lomlim, L;Saramunee, K
设计了用于5-氨基水杨酸(5-ASA)结肠给药的水溶性聚酰胺-胺(PAMAM)树枝状大分子结合物。药物通过两个含有偶氮键的间隔物--对氨基苯甲酸(PABA)和对氨基马尿酸(PAH)结合到树状大分子上。含PABA和PAH间隔物的PAMAM树枝状大分子偶联物与大鼠盲肠内容物37℃孵育后，随时间逐渐释放5-ASA，24 h释药量分别为给药量的45.6%和57.0%。商品前药柳氮磺吡啶的释药速度明显快于两种结合物的释药速度(6h释放量的80.2%)。从树状大分子结合物与胃匀浆或磷酸盐缓冲液(pH 1.2和6.8)孵育中未检测到5-ASA。两种结合物与小肠匀浆孵育12it后，仅发现少量的5-ASA。看来这种PAMAM树枝状大分子可以被开发为结肠定位给药的载体。(C)2002 Elsevier Science B.V.保留所有权利。
The water-soluble polyamidoamine (PAMAM) dendrimer conjugates for colonic delivery of 5-aminosalicylic acid (5-ASA) were designed. The drug was bound to the dendrimer using two different spacers containing azo-bond, p-aminobenzoic acid (PABA) and p-aminohippuric acid (PAH). Incubation of PAMAM dendrimer conjugates containing PABA and PAH spacers with rat cecal contents at 37 degreesC gradually released 5-ASA with time and the amount of drug released was 45.6 and 57.0% of the dose in 24 h, respectively. The release of the drug from the commercial prodrug, sulfasalazine was significantly faster than both conjugates (80.2% of the dose in 6 h). No 5-ASA was detected from the incubation of dendrimer conjugates with the homogenate of the stomach or phosphate buffer, pH 1.2 and 6.8. Only a small amount of 5-ASA was found after incubation of both conjugates with the homogenate of the small intestine for 12 It. It appears that this PAMAM dendrimer can be developed for use as a carrier for colon-specific drug delivery. (C) 2002 Elsevier Science B.V. All rights reserved.