# Preparation, Characterization, and Leishmanicidal Assessment of Silver- and Dapsone-Loaded Niosomes Co-administration: In Silico and In Vitro Study

## TL;DR

This study explores combining silver and dapsone in niosomes to treat leishmaniasis, showing promising in vitro and in silico results.

## Contribution

The novel approach combines silver and dapsone in niosomes, demonstrating synergistic anti-leishmanial effects.

## Key findings

- Silver and dapsone niosomes co-administration showed higher potency than amphotericin B.
- The combination triggered Th1-related immune responses and downregulated Th2 phenotypes.
- Molecular docking revealed strong binding affinity between dapsone and iNOS.

## Abstract

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.

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 in vivo and clinical studies.