Thiolated polymers -: thiomers:: development and in vitro evaluation of chitosan-thioglycolic acid conjugates
Thiolated polymers -: thiomers:: development and in vitro evaluation of chitosan-thioglycolic acid conjugates
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DOI：
10.1016/s0142-9612(00)00421-x
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发表时间：
2001-09-01
期刊：
影响因子：
14
通讯作者：
Bernkop-Schnürch, A
中科院分区：
文献类型：
--
作者：
Kast, CE;Bernkop-Schnürch, A
本研究的目的是通过共价连接巯基部分到这种阳离子聚合物来改善壳聚糖的粘膜粘附性能。通过碳二亚胺介导，巯基乙酸（TGA）共价连接到壳聚糖。这是通过在聚合物的伯氨基和TGA的羧酸基团之间形成酰胺键来实现的。取决于pH值和偶联反应期间聚合物与TGA的重量比，得到的硫醇化聚合物，即所谓的硫代异构体，每克聚合物显示出6.58、9.88、27.44和38.23 μ mol硫醇基团。用这些壳聚糖-TGA缀合物在新鲜切除的猪肠粘膜上进行的拉伸研究表明，与未改性的聚合物相比，总粘附功（TWA）分别增加了6.3倍、8.6倍、8.9倍和10.3倍。相比之下，壳聚糖和游离未缀合的TGA的组合显示几乎没有粘膜粘附。这些数据与通过另一种粘膜粘附试验获得的进一步结果具有良好的相关性，该试验表明巯基化壳聚糖在猪粘膜上的停留时间延长。因此，所有缀合物的溶胀行为与以相同方式预处理的未改性聚合物完全在相同的范围内。此外，可以表明壳聚糖-TGA缀合物仍然是可被糖苷酶溶菌酶生物降解的。根据这些结果，壳聚糖-TGA缀合物代表了一种有前途的工具，用于开发粘膜粘附药物递送系统。(C)2001爱思唯尔科技有限公司版权所有。
The aim of this study was to improve mucoadhesive properties of chitosan by the covalent attachment of thiol moieties to this cationic polymer. Mediated by a carbodiimide, thioglycolic acid (TGA) was covalently attached to chitosan. This was achieved by the formation of amide bonds between the primary amino groups of the polymer and the carboxylic acid group of TGA. Dependent on the pH-value and the weight ratio of polymer to TGA during the coupling reaction the resulting thiolated polymers, the so-called thiomers, displayed 6.58, 9.88, 27.44, and 38.23 mu mole thiol groups per gram polymer. Tensile studies carried out with these chitosan-TGA conjugates on freshly excised porcine intestinal mucosa demonstrated a 6.3-, 8.6-, 8.9-, and 10.3-fold increase in the total work of adhesion (TWA) compared to the unmodified polymer, respectively. In contrast, the combination of chitosan and free unconjugated TGA showed almost no mucoadhesion. These data were in good correlation with further results obtained by another mucoadhesion test demonstrating a prolonged residence time of thiolated chitosan on porcine mucosa. The swelling behavior of all conjugates was thereby exactly in the same range as for an unmodified polymer pretreated in the same way. Furthermore, it could be shown that chitosan-TGA conjugates are still biodegradable by the glycosidase lysozyme. According to these results, chitosan-TGA conjugates represent a promising tool for the development of mucoadhesive drug delivery systems. (C) 2001 Elsevier Science Ltd. All rights reserved.