Biocompatible silver nanoparticles reduced from Anethum graveolens leaf extract augments the antileishmanial efficacy of miltefosine

Abstract

Despite the existence of chemotherapy, there is no effective cure for leishmaniasis. In the light of recommended therapeutic regimen is attributed for toxicity and development of clinical resistance, exploration of an efficient method of drug delivery could be one of the option in reducing the dosage and toxicity of drugs. This work is aimed in such fashion to study the enhanced antileishmanial activity of miltefosine with silver-nanoparticles (AgNPs) synthesized by using Anethum graveolens (dill) leaf extract as reducing agent. AgNPs were synthesized in a single step process and characterized by UV-visible, X-ray diffraction (XRD), Fourier transform infra-red spectroscopy (FTIR) to understand the crystal structure and functional groups on their surface. TEM analysis showed that the synthesized AgNPs are of an average size of 35 nm. By performing MTT assay, we found that, AgNPs (between 20 and 100 μM) are biocompatible in nature through pertaining >80% viability of macrophages. Furthermore, AgNPs alone (50 μM) have not shown antileishmanial effect on promastigote stage of Leishmania parasite but in combination with miltefosine (12.5 μM and 25 μM), it magnifies the leishmanicidal effect of miltefosine by ∼2-folds (i.e. AgNPs cut down the IC50 of miltefosine about to half). Scanning electron microscopic (SEM) observation for morphological aberration and genomic DNA fragmentation in promastigotes confirmed the enhanced effect of meltefosine in combination with AgNPs (50 μM AgNPs plus 12.5 μM miltefosine). Similarly, this combination has likely shown a slight augmentation (p = 0.057) of miltefosine (2.5 μM) leishmanicidal efficacy on amastigote stage of the parasite in infected human macrophages by reducing their intracellular growth.