Rolón Miriam, Serrano Dolores R, Lalatsa Aikaterini, de Pablo Esther, Torrado Juan Jose, Ballesteros Maria Paloma, Healy Anne Marie, Vega Celeste, Coronel Cathia, Bolás-Fernández Francisco, Dea-Ayuela Maria Auxiliadora
Centro para el Desarrollo de la Investigación Científica (CEDIC) , Manduvirá 635 entre 15 de Agosto y O'Leary, 1255 Asunción, Paraguay.
Departamento de Farmacia y Tecnología Farmacéutica, Facultad de Farmacia, Universidad Complutense de Madrid , Plaza Ramón y Cajal s/n, 28040 Madrid, Spain.
Mol Pharm. 2017 Apr 3;14(4):1095-1106. doi: 10.1021/acs.molpharmaceut.6b01034. Epub 2017 Mar 3.
Chagas disease (CD) is a parasitic zoonosis endemic in most mainland countries of Central and South America affecting nearly 10 million people, with 100 million people at high risk of contracting the disease. Treatment is only effective if received at the early stages of the disease. Only two drugs (benznidazole and nifurtimox) have so far been marketed, and both share various limitations such as variable efficacy, many side effects, and long duration of treatment, thus reducing compliance. The in vitro and in vivo efficacy of poly-aggregated amphotericin B (AmB), encapsulated poly-aggregated AmB in albumin microspheres (AmB-AME), and dimeric AmB-sodium deoxycholate micelles (AmB-NaDC) was evaluated. Dimeric AmB-NaDC exhibited a promising selectivity index (SI = 3164) against amastigotes, which was much higher than those obtained for licensed drugs (benznidazole and nifurtimox). AmB-AME, but not AmB-NaDC, significantly reduced the parasitemia levels (3.6-fold) in comparison to the control group after parenteral administration at day 7 postinfection. However, the oral administration of AmB-NaDC (10-15 mg/kg/day for 10 days) resulted in a 75% reduction of parasitemia levels and prolonged the survival rate in 100% of the tested animals. Thus, the results presented here illustrate for the first time the oral efficacy of AmB in the treatment of trypanosomiasis. AmB-NaDC is an easily scalable, affordable formulation prepared from GRAS excipients, enabling treatment access worldwide, and therefore it can be regarded as a promising therapy for trypanosomiasis.
恰加斯病（CD）是一种寄生虫人畜共患病，在中美洲和南美洲的大多数大陆国家流行，影响近1000万人，另有1亿人面临感染该病的高风险。只有在疾病早期接受治疗才有效。到目前为止，只有两种药物（苯硝唑和硝呋莫司）已上市，且两者都有各种局限性，如疗效不一、副作用多和治疗时间长，从而降低了依从性。评估了聚集体两性霉素B（AmB）、白蛋白微球包裹的聚集体AmB（AmB-AME）和二聚体AmB-脱氧胆酸钠胶束（AmB-NaDC）的体外和体内疗效。二聚体AmB-NaDC对无鞭毛体表现出有前景的选择性指数（SI = 3164），远高于已获许可药物（苯硝唑和硝呋莫司）的选择性指数。与对照组相比，感染后第7天经肠胃外给药后，AmB-AME而非AmB-NaDC显著降低了寄生虫血症水平（3.6倍）。然而，口服AmB-NaDC（10 - 15 mg/kg/天，持续10天）使寄生虫血症水平降低了75%，并使100%的受试动物存活率提高。因此，此处呈现的结果首次说明了AmB治疗锥虫病的口服疗效。AmB-NaDC是一种易于扩大生产规模、价格可承受的制剂，由公认安全的辅料制备而成，可在全球范围内用于治疗，因此可被视为锥虫病的一种有前景的治疗方法。
