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树枝状大分子聚酰胺-胺(PAMAM dendrimers)是近年来研究较为广泛的树状大分子之一,其表面具有大量可修饰的官能团,内部具有大量空腔,且具有良好的生物相容性、渗透性及稳定性,这些特点使PAMAM dendrimers在药物和基因载体等领域应用广泛,并可能成为新型吸收促进剂。为具体研究PAMAM dendrimers的促吸收作用,该课题选取甘草苷为模型药物,其具有补脾益气、解毒保肝等功效,但有研究表明其经口服后不易被胃肠道吸收,且存在首过效应等,生物利用度较低,因此在临床上尚未被广泛应用。该课题以体内肠道吸收的2个主要决定性因素溶解性和渗透性为核心,通过对甘草苷理化性质的研究,并辅以目前广泛应用的肠渗透性模型Caco-2单层细胞膜,对比分析了含或不含不同表面活性官能团的PAMAM dendrimers的甘草苷溶液跨Caco-2细胞膜转运量,并利用MTT试验分析比较了不同官能团的PAMAM dendrimers对细胞的毒性大小。结果显示,0.1%的G4代PAG能安全、有效的促进甘草苷吸收,并适合进一步开发成新型药用辅料。
Dendrimers PAMAM dendrimers, one of the most widely studied dendrimers in recent years, have a large number of functional groups on their surface, a large number of cavities inside, and have good biocompatibility. Permeability and stability, these characteristics make PAMAM dendrimers widely used in fields such as medicine and gene carrier, and may become new absorption promoters. In order to study the absorption promoting effect of PAMAM dendrimers, we select the glycyrrhizin as the model drug, which has the effects of invigorating the spleen and invigorating qi and detoxifying and protecting the liver. However, studies have shown that it is not easily absorbed by the gastrointestinal tract after oral administration and exists in the first Over effect, low bioavailability, it has not been widely used in clinical practice. Based on the solubility and permeability of the two main determinants of intestinal absorption in vivo, the subject studied the physico-chemical properties of glycyrrhizin supplemented by the Caco-2 monolayer cell membrane that is currently widely used in intestinal permeability and comparative analysis The transmembrance of glycyrrhizin solution of PAMAM dendrimers with or without different surface-active functional groups across the Caco-2 cell membrane was investigated. MTT assay was used to compare the cytotoxicity of PAMAM dendrimers with different functional groups. The results showed that 0.1% G4 PAG could safely and effectively promote the absorption of liquiritin and be suitable for further development into new pharmaceutical excipients.