Targeting normal and neoplastic tissues in the rat jejunum and colon with boronated, cationic acrylamide copolymers
Targeting normal and neoplastic tissues in the rat jejunum and colon with boronated, cationic acrylamide copolymers
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DOI：
10.1016/j.jconrel.2005.03.015
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发表时间：
2005-08-18
影响因子：
10.8
通讯作者：
Rubinstein, A
中科院分区：
文献类型：
--
作者：
Azab, AK;Srebnik, M;Rubinstein, A
以丙烯酰胺、N-丙烯酰-3-氨基苯硼酸和N-丙烯酰乙二胺为单体，合成了一系列硼化阳离子共聚物（阳离子部分），目的是将硼中子俘获疗法（BNCT）定位在大鼠肠腔侧上实验诱导的息肉中。（B）比较局部施用后氨基苯基硼酸（AP B）和聚合物AP B的整个大鼠身体分布;（c）测量微环境参数如pH值的影响，粘蛋白和阳离子的存在对APB-共聚物和大鼠肠上皮细胞之间的相互作用的影响。组织硼水平的直接分析表明，聚合的APB-结肠息肉中的摄取高于周围正常组织。然而，在两者中发现了类似数量的游离APB。当在大鼠的正常空肠和结肠中测试时，聚合物APB摄取与共聚物中阳离子单体的摩尔含量成正比。镁离子、游离硼阳离子单体和粘蛋白的存在以浓度依赖性方式干扰这种摄取。在pH 5、7和10时，APB在结肠息肉中的蓄积量与共聚物中阳离子单体的含量成反比，提示息肉周围粘液量的增加可能阻碍了聚合物与恶性组织的静电附着。
A series of boronated cationic copolymers, composed of different ratios of acrylamide, N-acryloyl-3-aminophenylboronic acid and N-acryloyl-diaminoethane (the cationic moiety), were prepared with the intention of localizing boron neutron capture therapy (BNCT) in experimentally induced polyps on the luminal side of the gut of the rat.The goals of this study were to: (a) test the effect of cationization of the boronated copolymers on their uptake by polyps and normal adjacent epithelium; (b) compare the whole rat body distribution of aminophenylboronic acid (APB) and polymeric APB after local application; (c) measure the effect of micro-environmental parameters such as pH, the presence of mucin and cations on the interaction between the APB-copolymers and the epithelium of the rat intestines.Direct analysis of tissue boron levels showed that polymeric APB-uptake was higher in the colonic polyps than in the surrounding normal tissues. Free APB, however, was found in similar quantities in both. When tested in the normal jejunum and colon of the rat, polymeric APB uptake was directly proportional to the molar content of the cationic monomer in the copolymers. The presence of magnesium ions, free boron cationic monomer and mucin interfered with this uptake in a concentration-dependent manner. The uptake was pH-independent at pH 5, 7 and 10.APB accumulation in the colon polyps was inversely proportional to the cationic monomer content in the copolymers, suggesting an increased amount of mucus around the polyps, which probably impeded the electrostatic attachment of the polymer to the malignant tissue.