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Saurabh Kumar

Bio: Saurabh Kumar is an academic researcher from Department of Biotechnology. The author has contributed to research in topics: Medicine & In vivo. The author has an hindex of 1, co-authored 4 publications receiving 22 citations.

Papers
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Journal ArticleDOI
TL;DR: GNP-based delivery of AmB can be a better, cheaper, and safer alternative than available AmB formulations, and improved antileishmanial efficacy and reduced cytotoxicity.
Abstract: Background Amphotericin B (AmB) as a liposomal formulation of AmBisome is the first line of treatment for the disease, visceral leishmaniasis, caused by the parasite Leishmania donovani. However, nephrotoxicity is very common due to poor water solubility and aggregation of AmB. This study aimed to develop a water-soluble covalent conjugate of gold nanoparticle (GNP) with AmB for improved antileishmanial efficacy and reduced cytotoxicity. Methods Citrate-reduced GNPs (~39 nm) were functionalized with lipoic acid (LA), and the product GNP-LA (GL ~46 nm) was covalently conjugated with AmB using carboxyl-to-amine coupling chemistry to produce GNP-LA-AmB (GL-AmB ~48 nm). The nanoparticles were characterized by dynamic light scattering, transmission electron microscopy (TEM), and spectroscopic (ultraviolet-visible and infrared) methods. Experiments on AmB uptake of macrophages, ergosterol depletion of drug-treated parasites, cytokine ELISA, fluorescence anisotropy, flow cytometry, and gene expression studies established efficacy of GL-AmB over standard AmB. Results Infrared spectroscopy confirmed the presence of a covalent amide bond in the conjugate. TEM images showed uniform size with smooth surfaces of GL-AmB nanoparticles. Efficiency of AmB conjugation was ~78%. Incubation in serum for 72 h showed <7% AmB release, indicating high stability of conjugate GL-AmB. GL-AmB with AmB equivalents showed ~5-fold enhanced antileishmanial activity compared with AmB against parasite-infected macrophages ex vivo. Macrophages treated with GL-AmB showed increased immunostimulatory Th1 (IL-12 and interferon-γ) response compared with standard AmB. In parallel, AmB uptake was ~5.5 and ~3.7-fold higher for GL-AmB-treated (P<0.001) macrophages within 1 and 2 h of treatment, respectively. The ergosterol content in GL-AmB-treated parasites was ~2-fold reduced compared with AmB-treated parasites. Moreover, GL-AmB was significantly less cytotoxic and hemolytic than AmB (P<0.01). Conclusion GNP-based delivery of AmB can be a better, cheaper, and safer alternative than available AmB formulations.

37 citations

Journal ArticleDOI
TL;DR: In this article, the role of physicochemical properties of a nanoscale delivery system is discussed and different ways of nano-formulation delivery ranging from liposome, niosomes, polymeric, metallic, solid-lipid NPs were updated along with the possible mechanisms of action against the parasite.

16 citations

Journal ArticleDOI
TL;DR: In this article, the efficacy and possible mechanism of action of 7,8-dihydroxyflavone (DHF) and DHF synthesized gold nanoparticles (GNPs) against the parasite Leishmania donovani were analyzed.

5 citations

Journal ArticleDOI
TL;DR: In this paper , two phytochemicals, viz. 2, 4 dihydroxy-5-(hydroxymethyl) benzoic acid (DHMBA), and quebrachitol (QBC), were identified with anti-parasitic activity.

2 citations

Posted ContentDOI
26 Jun 2020
TL;DR: Low cytotoxicity and high biological activity may provide an alternative but improved delivery of DHF whose solubility increases due to conjugation with GNP, which is equally effective against sensitive and drug-resistant strains of L. 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

1 citations


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TL;DR: New advances and new strategies used on leishmaniasis therapy addressing alternative and innovative treatment paths such as physical and local/topical therapies, combination or multi-drug uses, immunomodulation, drug repurposing, and the nanotechnology-based drug delivery systems are summarized.
Abstract: Leishmaniasis is one of the most important tropical neglected diseases according to the World Health Organization. Even after more than a century, we still have few drugs for the disease therapy and their great toxicity and side effects put in check the treatment control program around the world. Moreover, the emergence of strains resistant to conventional drugs, co-infections such as HIV/Leishmania spp., the small therapeutic arsenal (pentavalent antimonials, amphotericin B and formulations, and miltefosine), and the low investment for the discovery/development of new drugs force researchers and world health agencies to seek new strategies to combat and control this important neglected disease. In this context, the aim of this review is to summarize new advances and new strategies used on leishmaniasis therapy addressing alternative and innovative treatment paths such as physical and local/topical therapies, combination or multi-drug uses, immunomodulation, drug repurposing, and the nanotechnology-based drug delivery systems.Key points• The treatment of leishmaniasis is a challenge for global health agencies.• Toxicity, side effects, reduced therapeutic arsenal, and drug resistance are the main problems.• New strategies and recent advances on leishmaniasis treatment are urgent.• Immunomodulators, nanotechnology, and drug repurposing are the future of leishmaniasis treatment.

85 citations

Journal ArticleDOI
TL;DR: The role of gold nanoparticles to improve the sensitivity and specificity of ELISA, PCR and immuno-PCR assays is focused on.

59 citations

Journal ArticleDOI
TL;DR: The review of nanoparticles as a new method in leishmaniasis treatment indicates that incorporating nanoparticles with chemical drugs improves the quality, efficiency, and sustainability of drugs and reduces their costs.

46 citations

Journal ArticleDOI
TL;DR: A synopsis of mechanisms associated to drug resistance in (pyogenic) streptococci is presented and some innovative strategies as alternative to conventional antibiotics, such as bacteriocins, bacteriophage, and phage lysins, and metal nanoparticles are discussed.
Abstract: The pyogenic streptococci group includes pathogenic species for humans and other animals and has been associated with enduring morbidity and high mortality. The main reason for the treatment failure of streptococcal infections is the increased resistance to antibiotics. In recent years, infectious diseases caused by pyogenic streptococci resistant to multiple antibiotics have been raising with a significant impact to public health and veterinary industry. The rise of antibiotic-resistant streptococci has been associated to diverse mechanisms, such as efflux pumps and modifications of the antimicrobial target. Among streptococci, antibiotic resistance emerges from previously sensitive populations as result of horizontal gene transfer or chromosomal point mutations due to excessive use of antimicrobials. Streptococci strains are also recognized as biofilm producers. The increased resistance of biofilms to antibiotics among streptococci promote persistent infection, which comprise circa 80% of microbial infections in humans. Therefore, to overcome drug resistance, new strategies, including new antibacterial and antibiofilm agents, have been studied. Interestingly, the use of systems based on nanoparticles have been applied to tackle infection and reduce the emergence of drug resistance. Herein, we present a synopsis of mechanisms associated to drug resistance in (pyogenic) streptococci and discuss some innovative strategies as alternative to conventional antibiotics, such as bacteriocins, bacteriophage, and phage lysins, and metal nanoparticles. We shall provide focused discussion on the advantages and limitations of agents considering application, efficacy and safety in the context of impact to the host and evolution of bacterial resistance.

25 citations