Rodrigues J M, Bories C, Emery I, Fessi H, Devissaguet J P, Liance M
Laboratoire de Pharmacie Galénique et Biopharmacie, URA CNRS 1218, Université Paris XI, Chatenay-Malabry, France.
Int J Parasitol. 1995 Dec;25(12):1437-41. doi: 10.1016/0020-7519(95)00055-0.
The loading of poly (D, L-lactide) nanoparticles with ABZ has led us to evaluate the potential of this new colloidal drug delivery system against E. multilocularis, using a murine model of hepatic alveolar echinococcosis. ABZ-loaded nanoparticles had a monodisperse size distribution between 100 and 150 nm. The efficiency of drug loading to nanoparticles was over 97%. In vitro, at an ABZ concentration of 1.0 microgram ml-1, the formulation had no toxicity for peritoneal macrophages harvested from uninfected mice. In vivo, the ABZ-loaded nanoparticles exhibited no signs of toxicity at any of the doses tested. Intravenous injections of 6 mg kg-1 of bound ABZ to infected mice had an equivalent antiparasitic effect on the metacestode growth to that of a treatment with 1500 mg kg-1 of orally administered free ABZ. The parasite hepatic superficial size as well as the peritoneal metastatic burden was significantly reduced by these 2 courses of treatment, as compared to those of untreated mice. Our results should encourage further study in order to explain the absence of dose-dependent efficacy of ABZ-loaded nanoparticles demonstrated in the present study.
用阿苯达唑（ABZ）负载聚（D，L-丙交酯）纳米颗粒，促使我们利用肝泡型包虫病小鼠模型评估这种新型胶体药物递送系统抗多房棘球绦虫的潜力。负载ABZ的纳米颗粒粒径单分散，在100至150纳米之间。纳米颗粒的药物负载效率超过97%。在体外，当ABZ浓度为1.0微克/毫升时，该制剂对从未感染小鼠采集的腹腔巨噬细胞无毒性。在体内，负载ABZ的纳米颗粒在任何测试剂量下均未表现出毒性迹象。给感染小鼠静脉注射6毫克/千克结合型ABZ，对幼虫生长的抗寄生虫作用与口服1500毫克/千克游离ABZ治疗相当。与未治疗小鼠相比，这两种治疗方案显著降低了寄生虫肝脏表面大小以及腹腔转移负担。我们的结果应鼓励进一步研究，以解释本研究中负载ABZ的纳米颗粒不存在剂量依赖性疗效的原因。
