Biological and Life Sciences, School of Arts and Sciences, Central Campus, Ahmedabad University, Navrangpura, Ahmedabad, Gujarat 380009, India.
National Institute of Animal Biotechnology (NIAB), Opposite Journalist Colony, Near Gowlidoddy, Extended Q-City Road, Gachibowli, Hyderabad - 500032, Telangana, India.
ACS Appl Bio Mater. 2024 Sep 16;7(9):6239-6248. doi: 10.1021/acsabm.4c00835. Epub 2024 Aug 18.
Leishmaniasis, attributed to the protozoan parasite , manifests in diverse clinical forms, including cutaneous, mucocutaneous, and visceral leishmaniasis; VL constitutes a significant global health menace. Prevalent in tropical and subtropical regions, this affliction disproportionately impacts individuals below the poverty threshold, transmitted through the bite of female sandflies. Existing treatments, such as pentavalent antimony, miltefosine, and Amphotericin B, exhibit limitations. Despite the emergence of liposomal Amphotericin B (AmBisome) as a promising antileishmanial agent, its utility is impeded by adverse effects, elevated production expenses, and cytotoxicity. To address these challenges, our investigation introduces a potential remedy─a citrate-coated gold Amphotericin B nanoparticle formulation. Characterized using dynamic light scattering and transmission electron microscopy, this pioneering formulation exhibited efficacy against Ag83 promastigotes as demonstrated by MTT cell viability testing. Evaluating internal reactive oxygen species (ROS) levels and dual staining with acridine orange and ethidium bromide unveiled its consequential impact on cell death. Significantly, our study discloses this novel nanoformulation's unprecedented inhibition of the trypanothione reductase enzyme. The findings posit the citrate-coated gold Amphotericin B nanoformulation as a promising and targeted antileishmanial agent, representing potential advancements in leishmaniasis therapeutics.
利什曼病是由原生动物寄生虫引起的，表现为多种临床形式，包括皮肤利什曼病、黏膜皮肤利什曼病和内脏利什曼病；内脏利什曼病构成了重大的全球健康威胁。这种疾病流行于热带和亚热带地区，主要影响贫困线以下的人群，通过雌性沙蝇的叮咬传播。现有的治疗方法，如五价锑、米替福新和两性霉素 B，都存在局限性。尽管出现了脂质体两性霉素 B（AmBisome）作为一种有前途的抗利什曼病药物，但由于其副作用、高昂的生产成本和细胞毒性，其应用受到了限制。为了解决这些挑战，我们的研究提出了一种潜在的治疗方法——柠檬酸涂层金两性霉素 B 纳米颗粒制剂。该制剂采用动态光散射和透射电子显微镜进行了表征，MTT 细胞活力测试表明，该制剂对 Ag83 前鞭毛体具有疗效。评估细胞内活性氧（ROS）水平并用吖啶橙和溴化乙锭双重染色揭示了其对细胞死亡的重大影响。值得注意的是，我们的研究揭示了这种新型纳米制剂对硫氧还蛋白还原酶的前所未有的抑制作用。这些发现表明，柠檬酸涂层金两性霉素 B 纳米颗粒制剂是一种有前途的、有针对性的抗利什曼病药物，为利什曼病的治疗带来了潜在的进展。
