中文摘要：

以壳聚糖为母体，在其侧链氨基上引入阳离子型氨基酸——精氨酸，合成了一种新型的具有仿穿膜肽结构的壳聚糖衍生物——Ⅳ．精氨酸壳聚糖（N-arginine chitosan，ACS），并将其作为吸收促进剂，研究其对不同模型药物的透皮促渗作用。通过FT-IR、^1HNMR以及元素分析法确证了ACS的结构，同时采用MTT实验考察其安全性。结果表明：ACS在0～10000mg·L^-1内安全性能良好。采用傅里叶衰减全反射光谱（ATR-FTIR）技术研究ACS对皮肤角蛋白的二级结构以及角质层含水量的影响，结果表明：ACS改变了角质层分子的有序性排列，使角蛋白的堆积结构变得疏松，同时还增加了皮肤角质层的含水量。采用倒置荧光显微镜和细胞流式仪考察角质形成细胞对ACS的摄取，结果表明：ACS进入细胞的荧光量是壳聚糖的4～8倍。分别采用荷负电、电中性以及正电性的药物阿司匹林、单硝酸异山梨酯和盐酸特拉唑嗪为模型药物，考察ACS对这些不同电性药物的透皮促渗作用，结果表明：ACS对负电性药物阿司匹林具有明显促渗作用，对电中性药物单硝酸异山梨酯有一定促渗作用，对正电性药物特拉唑嗪的透皮吸收反而有抑制作用。活体成像技术研究结果表明：ACS能明显增强自发荧光的阴离子型药物——桑色素在活体小鼠体内的荧光量。以上实验结果表明：ACS作为一种新型的透皮吸收促渗剂，可以改变角质形成细胞的结构，并具有模拟穿膜肽的促吸收功能，增加药物的透皮吸收，同时对药物也有一定的选择性。

英文摘要：

The purpose of this study is to investigate the penetration effects and mechanism of N-arginine chitosan （ACS）. This novel transdermal enhancer with a mimetic structure of cell-penetration peptides was synthesized by introducing hydrophilic arginine groups to the amino-group on chitosan＇s side chain. The structure of ACS was confirmed by FT-IR, ^1H NMR and element analysis. In addition, attenuated total reflection fourier transform infrared spectroscopy （ATR-FTIR） was used to study the protein conformation and the water content of stratum corneum, and the result suggested that ACS can change the orderly arrangement of the molecules in the stratum corneum, making the stack structure of keratin become loose. And ACS can increase the water content of the stratum comeum. Inverted fluorescence microscope and flow cytometry were used to examine penetration effect of ACS on Haeat cell. The result confirmed that the uptake of ACS was enhanced with increased substitution degree of arginine by 4-8 folds compared to chitosan. In vitro penetration studies on three electrical types of drugs were carried out using three model drugs of negatively charged aspirin, positively charged terazosin and neutral drug isosorbide mononitrate by the method of Franz diffusion cells. The results showed that ACS has obviously penetration of the negatively charged drug aspirin, and certain penetration of neutral drug issorbide mononitrate, but inhibition of positively charged terazosin. In vivo imaging technology research results show that the ACS can significantly enhance the fluorescence intensity of morin, which is the auto-fluorescence anionic drug. These obtained results suggested that ACS, as a promising transdermal enhancer, can change the structure of the keratinocytes and analog penetrating peptides promote absorption, but have certain selectivity for the drug.