3种助溶剂对阿苯达唑和阿苯达唑亚砜体外抗包虫活性的影响

Effects of albendazole and albendazole sulfoxide dissolved with different cosolvents on Echinococcus granulosus protoscoleces and vesicles in vitro

目的评估二甲基亚砜(DMSO)、吐温80和二者混合溶液等3种助溶剂溶解阿苯达唑(ABZ)和阿苯达唑亚砜(ABZSX)对其体外抗细粒棘球绦虫幼虫作用的影响。方法采用高效液相色谱法测定吐温80、DMSO及二者混合溶液对阿苯达唑的助溶作用,并比较抗包虫效果。分别将DMSO、吐温80及其混合溶液溶解的ABZ和ABZSX饱和浓度药物溶液加入RPMI 1640培养基中,使DMSO、吐温80及其混合溶液的浓度达到1.0%、0.1%和1.0%+0.1%。用上述含药培养液体外培养细粒棘球蚴原头节和囊泡,并设空白对照组以及适当浓度的助溶剂对照组,隔天观察原头蚴死亡率,周期为10d;每5d观察囊泡的形态及塌陷率,周期为20d。结果各药物作用至第10d和20d时,联用DMSO及吐温80溶解的ABZ组和ABZSX组原头蚴死亡率及囊泡塌陷率分别为(57.9±6.1)%、(49.32±8.5)%和(58.56±5.34)%、(80.74±1.58)%,均显著高于单用助溶剂组(P<0.01);空白对照组和助溶剂组原头蚴死亡率及囊泡塌陷率均低于9%。结论当药物相同时,DMSO和吐温80混合助溶剂组的抗原头蚴及囊泡作用优于DMSO助溶剂组,DMSO助溶剂组优于吐温80助溶剂组;助溶剂一致时,抗原头蚴效果ABZ组优于ABZSX组,抗囊泡效果ABZSX组优于ABZ组。

Objective Albendazole （ABZ） and albendazole sulfoxide （ABZSX） were dissolved with 1% dimethyl sulfox ide （DMSO）, 0.1 TweenS0, or a mixture of DMSO and TweenS0 to investigate their anti-hydatid action on Echinococ- cus granulosus protoscoleces and E. granulosus vesicles. Methods High-performance liquid chromatography （HPLC） was used to examine dissolution of ABZ by Tween 80, DMSO, and a mixture of DMSO and TweenS0. RPMI1640 culture medium with saturated concentrations of ABZ and ABZSX was used to culture E. granulosus protoscoleces and vesicles. ABZ and ABZSX were dissolved with DMSO, Tween80, or a DMSO, TweenS0, and the mixture of DMSO and TweenS0 in mixture of DMSO and Tween80. The concentrations of the RPMI1640 culture medium were 1.0~, 0. 1~ and （i. 0^-q-0.1）~. Protoscoleces and vesicles cultured in medium with ABZ and ABZSX served as the blank control. Pro toscoleces and vesicles cultured in DMSO, TweenS0, or a mixture of DMSO and TweenS0 at each concentration served as the control. The percentage of dead E. granulosus protoscoleces in each group was tallied daily for 10 days. The percent age of disrupted vesicles in each sample was determined every 5 days until day 20. Result The mixture of DMSO and TweenS0 had greater action against E. granulosus protoscoleces and vesicles than did DMSO or TweenS0 on day 10 and day 20 of culturing. Dissolving ABX and ABZX with DMSO and TweenS0 resulted in death of （57.9±6.1） of the protoscoleces and disruption of （49.32±8.5）% of the vesicles; dissolving ABX and ABZX with DMSO and Tween80 resul- ted in death of （58.56±5.34）%0 of the protoscoleces and disruption of （80.74 ±1.58） of the vesicles. Thus, dissol- ving ABX and ABZX with both cosolvents together was markedly more effective than either cosolvent alone （P%0.01）. The percentage of dead protoscoleees and the percentage of disrupted vesicles in the blank control and cosolvents alone was less than 9~ （P〉0.05）, Conclusion When the same drug was used, the mixture of DMSO and Tweend0 had greater action against E. granulosus protoscoleces and vesicles than did than DMSO or Tween80 alone. When the same cosolvent was used, ABZ had greater action against E. granulosus protoscoleces than did ABZSX, and ABZSX had greater action a- gainst E. granuZosus vesicles than did ABZ.