Effects of Amphotericin B-Conjugated Functionalized Carbon Nanoparticles in the Treatment of Cutaneous Leishmaniasis.

IF 1.4 4区 医学 Q4 IMMUNOLOGY Parasite Immunology Pub Date : 2024-10-01 DOI:10.1111/pim.13068
Maryam Heidari-Kharaji, Suisha Suruwb Guerra, Robinson Pavene Puneiad
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Abstract

Leishmaniasis is a parasitic disease spread by the bite of an infected sandfly and caused by protozoan parasites of the genus Leishmania. Currently, there is no vaccine available for leishmaniasis in humans, and the existing chemotherapy methods face various clinical challenges. The majority of drugs are limited to a few toxic compounds, with some parasite strains developing resistance. Therefore, the discovery and development of a new anti-leishmanial compound is crucial. One promising strategy involves the use of nanoparticle delivery systems to accelerate the effectiveness of existing treatments. In this study, Amphotericin B (AmB) was incorporated into functionalized carbon nanotube (f-CNT) and evaluated for its efficacy against Leishmania major in vitro and in a BALB/c mice model. The increase in footpad thickness was measured, and real-time PCR was used to quantify the parasite load post-infection. Levels of nitric oxide and cytokines IL-4 and IFN-γ were also determined. We found that f-CNT-AmB significantly reduced the levels of promastigotes and amastigotes of the Leishmania parasite. The nanoparticle showed strong anti-leishmanial activity with an IC50 of 0.00494 ± 0.00095 mg/mL for promastigotes and EC50 of 0.00294 ± 0.00065 mg/mL for amastigotes at 72 h post-infection, without causing harm to mice macrophages. Treatment of infected BALB/c mice with f-CNT-AmB resulted in a significant decrease in cutaneous leishmania (CL) lesion size in the foot pad, as well as reduced Leishmania burden in both lymph nodes and spleen. The levels of nitric oxide and IFN-γ significantly increased in the f-CNT-AmB treated groups. Also, our results showed that the level of IL-4 significantly decreased after f-CNT-AmB treatment in comparison to other groups. In conclusion, our results demonstrate that AmB loaded into f-CNT is significantly more effective than AmB alone in inhibiting parasite propagation and promoting a shift towards a Th1 response.

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两性霉素 B 键合功能化碳纳米粒子在治疗皮肤利什曼病中的效果。
利什曼病是一种通过被感染的沙蝇叮咬传播的寄生虫病,由利什曼原虫属寄生虫引起。目前,还没有针对人类利什曼病的疫苗,现有的化疗方法也面临各种临床挑战。大多数药物仅限于少数几种有毒化合物,一些寄生虫菌株会产生抗药性。因此,发现和开发新的抗利什曼病化合物至关重要。一种很有前景的策略是使用纳米颗粒给药系统来加快现有疗法的疗效。在这项研究中,将两性霉素 B (AmB) 加入功能化碳纳米管 (f-CNT) 中,并在体外和 BALB/c 小鼠模型中评估其对主要利什曼病的疗效。对脚垫厚度的增加进行了测量,并使用实时 PCR 对感染后的寄生虫载量进行了量化。此外,还测定了一氧化氮以及细胞因子 IL-4 和 IFN-γ 的水平。我们发现,f-CNT-AmB 能显著降低利什曼原虫和非原虫的水平。这种纳米粒子具有很强的抗利什曼病活性,在感染后 72 小时内,对原生体的 IC50 值为 0.00494 ± 0.00095 mg/mL,对非原生体的 EC50 值为 0.00294 ± 0.00065 mg/mL,且不会对小鼠的巨噬细胞造成伤害。用 f-CNT-AmB 处理受感染的 BALB/c 小鼠后,脚垫上的皮肤利什曼病(CL)病变面积显著减少,淋巴结和脾脏中的利什曼病负担也有所减轻。一氧化氮和 IFN-γ 的水平在 f-CNT-AmB 治疗组中明显升高。此外,我们的结果表明,与其他组相比,f-CNT-AmB 治疗组的 IL-4 水平明显下降。总之,我们的结果表明,在抑制寄生虫繁殖和促进向 Th1 反应转变方面,载入 f-CNT 的 AmB 比单独使用 AmB 更有效。
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来源期刊
Parasite Immunology
Parasite Immunology 医学-寄生虫学
CiteScore
4.70
自引率
4.50%
发文量
61
审稿时长
6-12 weeks
期刊介绍: Parasite Immunology is an international journal devoted to research on all aspects of parasite immunology in human and animal hosts. Emphasis has been placed on how hosts control parasites, and the immunopathological reactions which take place in the course of parasitic infections. The Journal welcomes original work on all parasites, particularly human parasitology, helminths, protozoa and ectoparasites.
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