de Barros Cristina Maria, Veloso Vanja Maria, Andrade Margareth Spangler, Vilela José Mário Carneiro, de Oliveira Maria Alice, de Lana Marta, Bahia Maria Terezinha, Mosqueira Vanessa Carla Furtado
Laboratory of Pharmaceutics and Nanotechnology, School of Pharmacy, Federal University of Ouro Preto, Campus Universitário Morro do Cruzeiro, Ouro Preto 35400-000, MG, Brazil.
Post-Graduation Program in Biological Sciences (NUPEB), Exact and Biological Sciences Institute (ICEB), Federal University of Ouro Preto, Ouro Preto 35400-000, MG, Brazil.
Pathogens. 2025 Mar 26;14(4):319. doi: 10.3390/pathogens14040319.
The therapeutic management of Chagas disease requires new medicines because the standard-of-care drugs available induce adverse effects and have limited efficacy. In this study, we developed a formulation of albaconazole (ABZ) loaded in biodegradable polymeric nanocapsules (NCs). Free ABZ and ABZ-loaded NCs were similarly active against the Y strain and inactive against the Colombian strain epimastigotes of . Infected mice were given ABZ in different doses and treatment schedules by oral, SC, and IM routes during the acute phase of infection. Free ABZ taken orally reduced parasitemia and suppressed mortality; however, all the animals maintained patent parasitemia during and after treatment. ABZ-NCs increased anti- effects ( < 0.05), inducing negative parasitemia during treatment in most of the tested regimens. The parasitemia level was also significantly reduced after treatment with ABZ-NCs during the acute phase of the disease, and relapses were delayed compared with the free ABZ treatment. Once- and twice-daily doses were similarly effective, demonstrating that the NCs prolonged the ABZ-NC residence time. Free ABZ and ABZ-NCs did not prevent infection, ABZ seemed to have suppressive effects on growth, and encapsulation prolonged this suppression. The analysis of the in vivo results indicated that the NCs significantly improved the safety of ABZ in the mouse model, suggesting that the increased ABZ-NC dosage regimen merits further efficacy and pharmacokinetic evaluations.
恰加斯病的治疗管理需要新的药物，因为现有的标准治疗药物会产生不良反应且疗效有限。在本研究中，我们开发了一种载于可生物降解聚合物纳米胶囊（NCs）中的阿巴康唑（ABZ）制剂。游离ABZ和载有ABZ的NCs对Y菌株的活性相似，而对克氏锥虫哥伦比亚株的前鞭毛体无活性。在感染急性期，通过口服、皮下和肌肉注射途径，给感染的小鼠给予不同剂量和治疗方案的ABZ。口服游离ABZ可降低寄生虫血症并抑制死亡率；然而，所有动物在治疗期间和治疗后均维持有明显的寄生虫血症。ABZ-NCs增强了抗虫效果（P<0.05），在大多数测试方案中，治疗期间诱导出现负寄生虫血症。在疾病急性期用ABZ-NCs治疗后，寄生虫血症水平也显著降低，与游离ABZ治疗相比，复发延迟。每日一次和两次给药同样有效，表明NCs延长了ABZ-NC的停留时间。游离ABZ和ABZ-NCs不能预防感染，ABZ似乎对克氏锥虫生长有抑制作用，而包封延长了这种抑制作用。体内结果分析表明，NCs显著提高了ABZ在小鼠模型中的安全性，提示增加ABZ-NC给药方案值得进一步进行疗效和药代动力学评估。
