Etemadifar Anna, Bahraminejad Sina, Pardakhty Abbas, Sharifi Iraj, Keyhani Alireza, Ranjbar Mehdi
Pharmaceutics Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran.
Leishmaniasis Research Center, Kerman University of Medical Sciences, Kerman, Iran.
Adv Pharm Bull. 2024 Dec 30;14(4):892-907. doi: 10.34172/apb.42740. Epub 2024 Dec 5.
Currently, there is a crucial need for alternative strategies to control leishmaniasis, which threatens more than 1 billion people worldwide. The simultaneous use of combination therapy and nanostructured lipid carriers aimed to assess the leishmanicidal activity of silver and dapsone niosomes co-administration and .
After preparing the niosomal formulations of dapsone and silver using the film hydration method, Span 40 and Tween 40/cholesterol with a 7/3 molar ratio was selected as the optimal formulation. Consequently, the arrays of experimental approaches were conducted to compare the anti-leishmaniasis efficacy of ready niosomes with amphotericin B and obtain a deeper understanding of their possible mechanisms of action.
Our findings showed higher potency of silver-loaded and dapsone-loaded niosomes co-administration compared to amphotericin B as a positive control group. The results of isobologram and combination index (CI) analyses confirmed the synergic potential of this mixture. This combination triggered anti-leishmanial pathways of macrophages, which promoted the expression level of Th1 cell-related genes, and the downregulated expression of the phenotypes related to Th2 cells. Furthermore, a high level of antioxidant and apoptotic profiles against the parasite provides a rational basis and potential drug combination for cutaneous leishmaniasis. Moreover, the outcomes of the molecular docking showed a high binding affinity between dapsone and iNOS, stimulating the immune response in Th1 direction.
In general, the multifunctional leishmanicidal activity of dapsone and silver-niosomes co-administration should be considered for further and clinical studies.
目前，迫切需要控制利什曼病的替代策略，利什曼病威胁着全球超过10亿人。联合使用联合疗法和纳米结构脂质载体旨在评估银和氨苯砜脂质体共同给药的杀利什曼原虫活性。
采用薄膜水化法制备氨苯砜和银的脂质体制剂后，选择摩尔比为7/3的司盘40和吐温40/胆固醇作为最佳制剂。因此，进行了一系列实验方法，以比较现成脂质体与两性霉素B的抗利什曼病疗效，并更深入地了解其可能的作用机制。
我们的研究结果表明，与作为阳性对照组的两性霉素B相比，载银和载氨苯砜脂质体共同给药的效力更高。等效线图和联合指数（CI）分析结果证实了该混合物的协同潜力。这种组合触发了巨噬细胞的抗利什曼原虫途径，促进了Th1细胞相关基因的表达水平，并下调了与Th2细胞相关的表型表达。此外，针对该寄生虫的高水平抗氧化和凋亡特征为皮肤利什曼病提供了合理依据和潜在的药物组合。此外，分子对接结果显示氨苯砜与诱导型一氧化氮合酶（iNOS）之间具有高结合亲和力，刺激Th1方向的免疫反应。
总体而言，氨苯砜和银脂质体共同给药的多功能杀利什曼原虫活性应进一步进行临床前和临床研究。
