Laboratory of Applied Toxinology on Antiparasitic Drugs, Department of Parasitology, Instituto Adolfo Lutz, Av Dr Arnaldo 355, 8 degrees andar, CEP 01246-000 São Paulo, Brazil.
Int J Antimicrob Agents. 2010 Aug;36(2):159-63. doi: 10.1016/j.ijantimicag.2010.04.006. Epub 2010 May 31.
Drug delivery systems are promising pharmaceutical formulations used to improve the therapeutic index of drugs. In this study, we developed a liposomal formulation of furazolidone that targets Leishmania (Leishmania) chagasi amastigotes in a hamster model. Using laser scanning confocal microscopy, it was demonstrated that the liposomal drug co-localised with L. (L.) chagasi amastigotes within macrophages. Liposomal furazolidone administered intraperitoneally at 0.5mg/kg for 12 consecutive days reduced spleen (74%) and liver (32%) parasite burden at a 100-fold lower dose than the free drug. Free furazolidone (50mg/kg) also effectively reduced spleen (82.5%) and liver (85%) parasites; its in vitro activity against promastigotes and intracellular amastigotes demonstrated a high degree of parasite selectivity. Thus, furazolidone, both in the free and liposome-loaded formulation, is an effective inhibitor of L. (L.) chagasi, representing a possible cost-effective drug candidate for the treatment of visceral leishmaniasis.
药物传递系统是一种有前途的药物制剂，用于提高药物的治疗指数。在这项研究中，我们开发了一种针对利什曼原虫（Leishmania） chagasi 无鞭毛体的呋喃唑酮脂质体配方，在仓鼠模型中。通过激光扫描共聚焦显微镜，证明脂质体药物与巨噬细胞内的 L.（L.）chagasi 无鞭毛体共定位。脂质体呋喃唑酮以 0.5mg/kg 的剂量腹腔内给药连续 12 天，在低 100 倍剂量下即可降低脾脏（74%）和肝脏（32%）寄生虫负荷。游离呋喃唑酮（50mg/kg）也能有效降低脾脏（82.5%）和肝脏（85%）寄生虫；其对前鞭毛体和细胞内无鞭毛体的体外活性表现出高度的寄生虫选择性。因此，游离呋喃唑酮和负载脂质体的呋喃唑酮都是利什曼原虫（L.） chagasi 的有效抑制剂，是治疗内脏利什曼病的一种有成本效益的候选药物。
