吐温80和二甲基亚砜对原头蚴的细胞毒性及对阿苯达唑的助溶作用研究

Study of the cytotoxicity to protoscoleces of tween 80 and dimethyl sulfoxide and the ability of tween 80 and dimethyl sulfoxide to increase the solubility of albendazole

目的探讨吐温80和二甲基亚砜(DMSO)对细粒棘球绦虫原头蚴的毒性和对阿苯达唑的助溶作用,筛选出适宜浓度的低毒性助溶剂,以便用于水溶性差的抗包虫病药物的筛选。方法采用伊红染色法检测吐温80和DMSO对细粒棘球绦虫原头蚴体外的细胞毒性;采用高效液相色谱法测定吐温80和DMSO对阿苯达唑的助溶作用。结果2种助溶剂对原头蚴的细胞毒性随浓度的增大而増强;低浓度的吐温80(0.05g/100ml和0.1g/100ml)对原头蚴无明显细胞毒性,低浓度的DMSO(0.5g/100ml和1.0g/100ml)几乎无细胞毒性(P<0.05);二者对阿苯达唑的助溶作用随着浓度的增加而增大,其中以0.1g/100ml吐温80和浓度为1.0g/100mlDMSO为溶剂时阿苯达唑的溶解度分别是(7.47±0.11)μg/100ml和(0.77±0.15)μg/100ml。结论在原头蚴体外药物干预试验中,≤0.1g/100ml吐温80溶液和≤1.0g/100ml的DMSO溶液可作为阿苯达唑的助溶剂。该浓度的助溶剂对原头蚴的毒性较低。

Objectives This study determined the toxicity of tween 80 and dimethyl sulfoxide to Echinococcus granulo- sus protoscoleces and their ability to increase the solubility of albendazole in order to select suitable concentrations of less toxic surfactants. Such surfactants will allow less soluble drugs to be used to kill protoscoleces. Methods Hematoxy- lin-eosin staining was used to measure the cytotoxicity to E. granulosus protoscoleces of tween 80 and dimethyl sulfoxide in vitro. High-performance liquid chromatography was used to examine the ability of Tween 80 and dimethyl sulfoxide to increase the solubility of albendazole. Results The cytotoxicity to protoscoleces of the two surfactants increased as their concentration increased. Low concentrations of tween 80 （0.05g/ml and 0. lg/ml） had no obvious cytotoxic effect on pro toscoleces, and the same was true for low concentrations of dimethyl sulfoxide （0.5 g/ml and 1.0 g/ml） （P〈0.05）. The two surfactants helped to increase the solubility of albendazole as their concentration increased. Tween80 （0.1 g/100 ml） increased the solubility of albendazole to （7.47±0.11） μg/100ml and dimethyl sulfoxide （1.0 g/100 ml） increased it to （0.77±0.15） μg/100ml. Conclusion Tween 80 （40. lg/100ml） and dimethyl sulfoxide （41.0 g/100 ml） can be used as cosolvents of albendazole. These concentrations of tween80 and dimethyl sulfoxide are less toxic to E. granulosus pro- toscoleces.