Potential therapeutic effects of curcumin coated silver nanoparticle in the treatment of cutaneous leishmaniasis due to Leishmania major in-vitro and in a murine model

Background: Leishmaniasis is a destructive protozoan parasitic and vector-borne infection characterized as a neglected tropical disease (NTD) that is currently endemic in more than 100 countries. Herbal compounds such as curcumin derived from turmeric with complex and extensive structures have a wide range of applications in the treatment of parasitic infections; however, its usage has a major challenge due to low water solubility and bioavailability. Besides, metal nanoparticles such as silver have been applied for parasitic infection treatment. Synthesis of curcumin and silver nanoparticles conjugate facilitates in enhancing curcumin solubility and bioavailability. Here curcumin-coated silver nanoparticles (Cur@AgNPs) were synthesized, characterized, and then their cell cytotoxicity and antileishmanial activities were investigated both in-vitro and in mouse models.Materials and methods: Curcumin coated silver nanoparticles (Cur@AgNPs) synthesized by a simple one-pot green chemistry technique. After confirming their stability, in vitro cell cytotoxicity and leishmanicidal activity against promastigotes and amastigotes of the protozoan parasite, Leishmania major (L. major) was evaluated by using colourimetric yellow methyl thiazole tetrazolium (MTT) assay. Furthermore, antiparasitic properties of Cur@AgNPs in the mouse model were studied through quantifying footpads (FPs) lesion size and determining parasite burden in lymph nodes (LNs) and FPs of infected BALAB/c mice with L. major.Results: Cur@AgNPs represent a plasmonic peak of silver nanoparticles at 420 nm in UV-Vis spectra. The size of synthesized NPs was 29.1 +/- 5.6 nm based on the analyzing TEM micrographs. The hydrodynamic diameter of the synthesized particles is 32.4 +/- 2.3 nm. The zeta potential of washed Cur@AgNPs (4 rounds of washing) was-19.8 +/- 1.5 mV. The stability of Cur@AgNPs at different time intervals (up to two months) in PBS buffer media has been investigated thoroughly. We confirmed that Cur@AgNPs decreased significantly in both forms of promastigotes and amastigotes of Leishmania parasite in a single treatment. The nanoparticle elucidated potent antileishmanial activity with IC50 of 58.99 mu g/ml for promastigotes and EC50 58.99 mu g/ml for amastigotes at 48 h post-infection with no harmful negative toxicity on the mice macrophages. In the treated infected BALB/c mice using Cur@AgNPs, the cutaneous leishmania (CL) lesion size in the FPs and Leishmania burden in both LNs and FPs were decreased significantly.Conclusion: The results of this study revealed that Cur@AgNPs could be, novel, safe, and effective promising candidates as an antileishmanial agent in the treatment of CL infection.