Tanvi Payal

Bio: Tanvi Payal is an academic researcher from Department of Biotechnology. The author has an hindex of 1, co-authored 2 publications receiving 2 citations.

Synthesis of 7, 8 –dihydroxyflavone functionalized gold nanoparticles and its mechanism of action against Leishmania donovani

Abstract: Abstract Background – The synthesis of gold nanoparticles (GNPs) using drugs, synthetic and natural compounds, proteins, nucleic acids have become beneficial due to improved biological activity coupled with reduced cytotoxicity. In this regard, green synthesis of GNPs using plant extract enriched with flavonoids has shown increased attention due to improved antimicrobial efficacy, greater solubility, and better bioavailability of the flavonoid conjugated with GNPs. We have used 7, 8 dihydroxyflavone (DHF), a flavonoid that is enriched in plants and known for neurotropic and antioxidant activities, for the synthesis of GNP. In this report, we have investigated synthesis, characterization, and biological activity of DHF synthesized GNP against parasite Leishmania donovani . Results – Synthesized DHF functionalized GNPs (DHF-GNPs) are ~35 nm in size with zeta potential values of -34.1 mV, as observed from DLS studies. UV-Visible spectroscopy and FT-IR analysis confirms successful conjugation of DHF over GNP. TEM imaging shows uniform size and spherical distribution of NPs. Against L. donovani promastigotes IC 50 for DHF and DHF-GNP is ~140 µM and ~40 µM respectively. In ex vivo amastigote model, IC 50 for DHF and DHF-GNP is ~40 µM and ~22 µM respectively. Even with 1000 µM of DHF-GNP, cytotoxicity is only ~30% on THP1 cells indicating its high biocompatibility. In DHF-GNP treated parasites, activity of arginase decreases in a dose-dependent manner as evident from gene expression and enzyme-based studies. Supplementation of treated cells with ornithine, metabolite of arginase, shows the highest recovery from death. This indicates inhibition of arginase as the main reason for parasite death. Induction of IFN-γ and reduction IL-12 cytokine response shows a possible T h 1/T h 2-mediated cell death. Also, DHF and DHF-GNP are equally effective against sensitive and drug-resistant strains of L. donovani . Conclusion – Low cytotoxicity and high biological activity may provide an alternative but improved delivery of DHF whose solubility increases due to conjugation with GNP. Further efficacy against drug-resistant strains could be beneficial instead of conventional chemotherapy for leishmaniasis. Keywords : Functionalized gold nanoparticle, DHF, DHF-GNP, arginase inhibition, drug-resistant Parasite, iNOS activation

Limitations of current chemotherapy and future of nanoformulation-based AmB delivery for visceral leishmaniasis—An updated review

Abstract: Visceral leishmaniasis (VL) is the most lethal of all leishmaniasis diseasesand the second most common parasiticdisease after malaria and,still, categorized as a neglected tropical disease (NTD). According to the latest WHO study, >20 Leishmania species spread 0.7–1.0 million new cases of leishmaniasis each year. VL is caused by the genus, Leishmania donovani (LD), which affects between 50,000 and 90,000 people worldwide each year. Lack of new drug development, increasing drug resistance, toxicity and high cost even with the first line of treatmentof Amphotericin B (AmB), demands new formulation for treatment of VLFurther the lack of a vaccine, allowedthe researchers to develop nanofomulation-based AmB for improved delivery. The limitation of AmB is its kidney and liver toxicity which forced the development of costly liposomal AmB (AmBisome) nanoformulation. Success of AmBisome have inspired and attracted a wide range of AmB nanoformulations ranging from polymeric, solid lipid, liposomal/micellar, metallic, macrophage receptor-targetednanoparticles (NP) and even with sophisticated carbon/quantum dot-based AmBnano delivery systems. Notably, NP-based AmB delivery has shown increased efficacy due to increased uptake, on-target delivery and synergistic impact of NP and AmB. In this review, we have discussed the different forms of leishmaniasis disease and their current treatment options with limitations. The discovery, mechanism of action of AmB, clinical status of AmB and improvement with AmBisome over fungizone (AmB-deoxycholate)for VL treatment was further discussed. At last, the development of various AmB nanoformulation was discussed along with its adavantages over traditional chemotherapy-based delivery. Graphical Abstract The nanoparticles with different size, shape and structure for drug delivery against Leishmania donovani.

The advantages of nanomedicine in the treatment of visceral leishmaniasis: between sound arguments and wishful thinking.

Abstract: Introduction: Although life-threatening if left untreated, visceral leishmaniasis (VL) is still a neglected endemic disease in 98 countries worldwide. The number of drugs available is low and few a...

Some Nanocarrier’s Properties and Chemical Interaction Mechanisms with Flavones

Abstract: Flavones such as 7,8-dihydroxyflavone (tropoflavin), 5,6,7-trihydroxyflavone (baicalein), 3′,4′,5,6-tetrahydroxyflavone (luteolin), 3,3′,4′,5,5′,7-hexahydroxyflavone (myricetin), 4′,5,7-trihydroxyflavone (apigenin), and 5,7-dihydroxyflavone (chrysin) are important both for their presence in natural products and for their pharmacological applications. However, due to their chemical characteristics and their metabolic processes, they have low solubility and low bioavailability. Knowledge about the physicochemical properties of nanocarriers and the possible mechanisms of covalent and non-covalent interaction between nanoparticles (NPs) and drugs is essential for the design of nanocarriers to improve the bioavailability of molecules with pharmacological potential, such as tropoflavin, baicalein, luteolin, myricetin, apigenin, and chrysin. The parameters of characterization of some NPs of these flavones, such as size, polydispersity index (PDI), zeta potential, encapsulation efficiency (EE), and % release/time, utilized in biomedical applications and the covalent and non-covalent interactions existing between the polymeric NPs and the drug were analyzed. Similarly, the presence of functional groups in the functionalized carbon nanotubes (CNTs), as well as the effect of pH on the % adsorption of flavonoids on functionalized multi-walled carbon nanotubes (MWCNT-COOH), were analyzed. Non-covalent interaction mechanisms between polymeric NPs and flavones, and covalent interaction mechanisms that could exist between the NPs and the amino and hydroxyl functional groups, are proposed.

Toward New Antileishmanial Compounds: Molecular Targets for Leishmaniasis Treatment

Abstract: The leishmaniases are a group of diseases caused by protozoan parasites—Leishmania sp. Leishmaniasis is classified among the 20 neglected diseases by WHO. Although the disease has been known for more than 120 years, the number of drugs used for the treatment is still limited to 5–6. The first-line drugs against leishmaniasis are pentavalent antimonials, which were introduced to the treatment 70 years ago—despite all their side effects. Molecular targets are becoming increasingly important for efficacy and selectivity in postgenomic drug research studies. In this chapter, we have discussed potential therapeutic targets of antileishmanial drug discovery such as pteridine reductase (PTR1), trypanothione reductase (TR), N-myristoyltransferase (NMT), trypanothione synthetase (TryS), IU-nucleoside hydrolase, and topoisomerases, enzymes and their inhibitors reported in the literature.