Synergistic Effect of Copper Nanoparticles and Paromomycin in the Treatment of Cutaneous Leishmaniasis.

Abstract

The interest in nanotechnology applications in medicine, particularly for combating microbial infections, has surged in recent years. This study investigated the in vitro and in vivo antileishmanial effects of copper nanoparticles (CuNPs) that were green synthesised using Capparis spinosa fruit extract, both on their own and in conjunction with paromomycin (PM). CuNPs were synthesised from a methanolic extract of C. spinosa. We assessed the in vitro antileishmanial activity of CuNPs (10-200 μg/mL) as well as the same concentrations of CuNPs (10-200 μg/mL) combined with PM (10-200 μg/mL), targeting the promastigote and amastigote forms of Leishmania major. Additionally, we evaluated the cytotoxic effects of CuNPs on THP1 cells. Subsequently, we tested these formulations on female BALB/c mice infected with L. major. The study measured footpad swelling, quantified parasite load through real-time PCR, and assessed levels of cytokines such as interleukin-4 (IL-4) and gamma interferon (IFN-ɤ), nitric oxide (NO), and arginase (ARG). The results demonstrated that CuNPs, particularly when combined with PM, significantly inhibited (p < 0.001) the growth of L. major promastigotes and amastigotes and stimulated IFN-ɤ, NO production and reduced IL-4 and ARG levels (p < 0.05). Importantly, CuNPs exhibited minimal cytotoxicity towards THP1 cells. In infected mice, the treatment with CuNPs, notably in combination with PM, resulted in a significant (p < 0.05) reduction in the mean number of parasites. Treatment with CuNPs at concentrations of 100 and 200 mg/mL led to a decrease in lesion diameter. The results of this study highlight the potent antileishmanial activity and synergistic effects of CuNPs, both alone and in combination with PM, against L. major promastigotes and amastigote forms, as well as their potential in treating cutaneous leishmaniasis (CL) in BALB/c mice.