He Wen, Guo Xianxi, Zhang Mian
Department of Pharmacy of Renmin Hospital, Wuhan University, Wuhan 430060, People's Republic of China.
Int J Pharm. 2008 May 22;356(1-2):82-7. doi: 10.1016/j.ijpharm.2007.12.050. Epub 2008 Feb 6.
The aim of this study was to evaluate the transdermal permeation enhancement of N-trimethyl chitosan (TMC) with different degrees of quaternization (DQ). TMCs with DQ of 40 and 60% (TMC40 and TMC60) were synthesized and characterized by (1)H NMR. Testosterone (TS) used as an effective drug, four different gels were prepared without enhancer, with 5% TMC40, 5% TMC60 or 2% Azone, respectively as enhancer. The effect of TMC60 on the stratum corneum was studied by Attenuated Total Reflection-Fourier Transform Infrared Spectroscopy (ATR-FTIR) combined with the technique of deconvolution. The results showed that TMC60 could significantly affect the secondary structure of keratin in stratum corneum. In vitro permeation studies were carried out using Franz-diffusion cells and in vivo studies were performed in rabbits. Both in vitro and in vivo permeation studies suggested the transdermal permeation enhancement of TMCs. Compared to the TS gel without enhancer, TS gels with enhancers all showed significant enhancing effect on transdermal permeation of TS (P<0.05). Meanwhile, compared to 2% Azone, 5% TMC60 had a stronger enhancement (P<0.05) while 5% TMC40 had a similar effect (P>0.05). The results suggested that the enhancement of TMCs increased with the increase of DQ.
本研究的目的是评估不同季铵化程度（DQ）的N-三甲基壳聚糖（TMC）对透皮渗透的增强作用。合成了季铵化程度为40%和60%的TMC（TMC40和TMC60），并通过¹H NMR进行表征。以睾酮（TS）作为有效药物，分别制备了不含促渗剂、含5% TMC40、5% TMC60或2%氮酮作为促渗剂的四种不同凝胶。采用衰减全反射傅里叶变换红外光谱（ATR-FTIR）结合去卷积技术研究了TMC60对角质层的影响。结果表明，TMC60能显著影响角质层中角蛋白的二级结构。使用Franz扩散池进行体外渗透研究，并在兔子身上进行体内研究。体外和体内渗透研究均表明TMC对透皮渗透有增强作用。与不含促渗剂的TS凝胶相比，含促渗剂的TS凝胶对TS的透皮渗透均有显著增强作用（P<0.05）。同时，与2%氮酮相比，5% TMC60的增强作用更强（P<0.05），而5% TMC40的效果相似（P>0.05）。结果表明，TMC的增强作用随DQ的增加而增加。
