Tabriz University of Medical Sciences Advanced Pharmaceutical Bulletin 2228-5881 14 4 2024 12 30 Preparation, Characterization, and Leishmanicidal Assessment of Silver- and Dapsone-Loaded Niosomes Co-administration: In Silico and In Vitro Study 892 907 10.34172/apb.42740 EN Anna Etemadifar https://orcid.org/0009-0003-7742-3810 Sina Bahraminejad https://orcid.org/0000-0001-7813-3004 Abbas Pardakhty Iraj Sharifi Alireza Keyhani Mehdi Ranjbar https://orcid.org/0000-0002-5844-3299 Journal Article 10.34172/apb.42740 2024 01 26 2024 12 03 Purpose: 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 in vitro and in silico. Methods: 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. Results: 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. Conclusion: In general, the multifunctional leishmanicidal activity of dapsone and silver-niosomes co-administration should be considered for further in vivo and clinical studies.