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

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.

Role of leptin in human visceral leishmaniasis?

Human visceral leishmaniasis (VL) is frequently found in poor population who are suffering from malnutrition in endemic areas. Therefore, obviously they may have reduced levels of leptin due to reduction in number of adipocytes which are major source of leptin production. Human pathogenesis of VL and reduced levels of leptin both are associated with increase in Th2 type immune response, characterized by secretion of cytokines such as IL-4 and IL-10. Whereas, the protective immune response during visceral leishmaniasis is associated with effective Th1 type immune response characterized by secretion of IFN-γ, IL-2 and IL-12, which correlates with leptin induction of T cells polarizing to Th1 population and secretion of proinflammatory cytokines, and also inhibition of Th2 type response. Therefore, we hypothesized that leptin might be effective in treatment of visceral leishmaniasis alone or VL patients who have co-infection with other immune deficiency syndromes such as AIDS/diabetes/autoimmune disorders by regulation of Th1/Th2 homeostasis.