Jintapattanakit Anchalee, Mao Shirui, Kissel Thomas, Junyaprasert Varaporn Buraphacheep
Department of Pharmacy, Faculty of Pharmacy, Mahidol University, Bangkok, Thailand.
Eur J Pharm Biopharm. 2008 Oct;70(2):563-71. doi: 10.1016/j.ejpb.2008.06.002. Epub 2008 Jun 17.
The aim of this research was to investigate the effect of degrees of quaternization (DQ) and dimethylation (DD) on physicochemical properties and cytotoxicity of N-trimethyl chitosan (TMC). TMC was synthesized by reductive methylation of chitosan in the presence of a strong base at elevated temperature and polymer characteristics were investigated. The number of methylation process and duration of reaction were demonstrated to affect the DQ and DD. An increased number of reaction steps increased DQ and decreased DD, while an extended duration of reaction increased both DQ and DD. The molecular weight of TMC was in the range of 60-550kDa. From the Mark-Houwink equation, it was found that TMC in 2% acetic acid/0.2M sodium acetate behaved as a spherical structure, approximating a random coil. The highest solubility was found with TMC of an intermediate DQ (40%) regardless of DD and molecular weight. The effect of DD on the physicochemical properties and cytotoxicity was obviously observed when proportion of DD to DQ was higher than 1. TMC with relatively high DD showed reduction in both solubility and mucoadhesion and hence decreased cytotoxicity. However, the influence of DD was insignificant when DQ of TMC was higher than 40% at which physicochemical properties and cytotoxicity were mainly dependent upon DQ.
本研究的目的是探究季铵化程度（DQ）和二甲基化程度（DD）对N-三甲基壳聚糖（TMC）理化性质和细胞毒性的影响。在强碱存在下，于高温条件下通过壳聚糖的还原甲基化反应合成了TMC，并对聚合物特性进行了研究。结果表明，甲基化过程的次数和反应持续时间会影响DQ和DD。反应步骤数增加会使DQ升高，DD降低，而反应持续时间延长则会使DQ和DD均升高。TMC的分子量在60 - 550 kDa范围内。根据马克-豪温克方程发现，TMC在2%乙酸/0.2M乙酸钠中表现为球形结构，近似无规线团。无论DD和分子量如何，中间DQ（40%）的TMC溶解度最高。当DD与DQ的比例高于1时，明显观察到DD对理化性质和细胞毒性的影响。具有相对较高DD的TMC在溶解度和黏膜粘附性方面均降低，因此细胞毒性也降低。然而，当TMC的DQ高于40%时，DD的影响不显著，此时理化性质和细胞毒性主要取决于DQ。
