Leonardi Darío, Echenique Claudia, Lamas María C, Salomon Claudio J
Area Tecnología Farmacéutica, Departamento Farmacia, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Suipacha 531, 2000 Rosario, Argentina.
J Antimicrob Chemother. 2009 Aug;64(2):375-8. doi: 10.1093/jac/dkp199. Epub 2009 Jun 4.
In vitro and in vivo experiments were used to determine whether albendazole-PEG 6000 solid dispersions would be effective in the treatment of Toxocara canis larva migrans.
Albendazole-PEG 6000 (1:1, 1:5 and 1:9 ratios) solid dispersions were prepared by the solvent evaporation method. The morphology of the particles was evaluated by scanning electron microsocopy (SEM), and in vitro dissolution assays were also carried out. Mice were infected with T. canis and then treated orally with albendazole-PEG 6000 systems or albendazole suspended in water. The anthelmintic effect was examined at 28 days post-infection (p.i.). The number of larvae recovered from mice treated with albendazole alone and those treated with albendazole-PEG 6000 were compared with the numbers from the placebo group.
Dissolution of albendazole from solid dispersions was markedly enhanced by increasing the polymer concentration. At a 1:9 drug:polymer ratio, >90% of the albendazole was dissolved in 10 min. SEM showed microparticles to be of small spherical shape compared with the pure components. In vivo evaluation of larva migration showed that both albendazole-PEG 6000 solutions exhibited a greater anthelmintic effect in the brain (0 larvae/mouse). In addition it was also found that liver and lung showed a significant decrease in the number of larvae. Evaluation of vehicle toxicity (PEG 6000 in water) showed a mice survival rate of 100% at the assayed concentrations.
These data suggest that albendazole-PEG 6000 solid dispersions markedly increased the effectiveness of albendazole against the migratory activity of larvae. Particularly, these polymeric solutions were able to totally prevent migration of larvae to the mouse brain.
通过体外和体内实验确定阿苯达唑 - 聚乙二醇6000固体分散体对犬弓首蛔虫幼虫移行症的治疗效果。
采用溶剂蒸发法制备阿苯达唑 - 聚乙二醇6000(比例为1:1、1:5和1:9)固体分散体。通过扫描电子显微镜(SEM)评估颗粒形态,并进行体外溶出度测定。将小鼠感染犬弓首蛔虫,然后口服阿苯达唑 - 聚乙二醇6000制剂或悬浮于水中的阿苯达唑进行治疗。在感染后28天检查驱虫效果。将单独用阿苯达唑治疗的小鼠和用阿苯达唑 - 聚乙二醇6000治疗的小鼠体内回收的幼虫数量与安慰剂组的数量进行比较。
随着聚合物浓度的增加,阿苯达唑从固体分散体中的溶出度显著提高。在药物与聚合物比例为1:9时,>90%的阿苯达唑在10分钟内溶解。扫描电子显微镜显示,与纯组分相比,微粒呈小球形。幼虫移行的体内评估表明,两种阿苯达唑 - 聚乙二醇6000溶液在脑内均表现出更大的驱虫效果(每只小鼠0条幼虫)。此外,还发现肝脏和肺中的幼虫数量显著减少。载体毒性评估(水中的聚乙二醇6000)显示,在所测定的浓度下小鼠存活率为100%。
这些数据表明,阿苯达唑 - 聚乙二醇6000固体分散体显著提高了阿苯达唑对幼虫移行活性的有效性。特别是,这些聚合物溶液能够完全防止幼虫向小鼠脑内移行。