仿生壳聚糖衍生物：N-精氨酸壳聚糖的制备、表征及经皮增强研究。

A biomimetic chitosan derivates: preparation, characterization and transdermal enhancement studies of N-arginine chitosan.

机构信息

Department of Pharmaceutics, China Pharmaceutical University, No. 24 tongjiaxiang Nanjing, China.

出版信息

Molecules. 2011 Aug 9;16(8):6778-90. doi: 10.3390/molecules16086778.

A novel arginine-rich chitosan (CS) derivates mimicked cell penetration peptides; N-Arginine chitosan (N-Arg-CS) was prepared by two reaction methods involving activated L-arginine and the amine group on the chitosan. FTIR spectra showed that arginine was chemically coupled with CS. Elemental analysis estimated that the degrees of substitution (DS) of arginine in CS were 6%, 31.3% and 61.5%, respectively. The drug adefovir was chosen as model and its permeation flux across excised mice skin was investigated using a Franz diffusion cell. The results showed that the most effective enhancer was 2% (w/v) concentration of 10 kDa N-Arg-CS with 6% DS. At neutral pH, the cumulative amount of adefovir permeated after 12 hours was 2.63 ± 0.19 mg cm(-2) which was 5.83-fold more than adefovir aqueous solution. Meanwhile N-Arg-CS was 1.83, 2.22, and 2.45 times more effective than Azone, eucalyptus and peppermint, respectively. The obtained results suggest that N-Arg-CS could be a promising transdermal enhancer.

一种新型精氨酸丰富的壳聚糖（CS）衍生物模拟细胞穿透肽；通过两种反应方法制备 N-精氨酸壳聚糖（N-Arg-CS），涉及到 L-精氨酸和壳聚糖上的氨基的活化。傅里叶变换红外光谱（FTIR）表明精氨酸与 CS 发生了化学偶联。元素分析估计 CS 中精氨酸的取代度（DS）分别为 6%、31.3%和 61.5%。选择阿德福韦酯作为模型，使用 Franz 扩散池研究其在离体小鼠皮肤中的渗透通量。结果表明，最有效的促进剂是 2%（w/v）浓度的 10 kDa N-Arg-CS，取代度为 6%。在中性 pH 值下，12 小时后阿德福韦酯的累积渗透量为 2.63±0.19 mg cm(-2)，是阿德福韦酯水溶液的 5.83 倍。同时，N-Arg-CS 比氮酮、桉树和薄荷油分别有效 1.83、2.22 和 2.45 倍。研究结果表明，N-Arg-CS 可能是一种有前途的透皮促进剂。