scispace - formally typeset
Search or ask a question
Journal ArticleDOI

Andrographolide engineered gold nanoparticle to overcome drug resistant visceral leishmaniasis.

TL;DR: This study aims to arrive at terpenoid andrographolide engineered gold nanoparticle (AGAunps) facile synthesis and its efficacy evaluations against wild and drug resistant VL strains for the first time.
Abstract: Visceral leishmaniasis (VL) is World Health Organization designated most serious leishmaniasis with an annual mortality rate of 50,000. Even after country specific eradication programs, the disease...
Citations
More filters
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


Additional excerpts

  • ...5-25) (1-108) (1-108) GNP (μg/mL) GL (μg/mL) AmB (μM) GL-AmB (μM) *** *** *** *** ***...

    [...]

Journal ArticleDOI
TL;DR: In this article, the authors discuss the overlapping connectivity and relevance of the two fields, including nanoaggregates generated in herbal medicine decoctions, the application of nanotechnology in the delivery and treatment of natural active ingredients, and the influence of physiological regulatory capability of traditional herbal medicine on the in vivo fate of nanoparticles.

37 citations

Journal ArticleDOI
TL;DR: This review reports on published studies related to microparticles (MPs) and nanoparticles (NPs) loaded with Andrographolide and improved bioavailability, target-tissue distribution, and efficacy of AG loaded in the described drug delivery systems have been reported.

34 citations

Journal ArticleDOI
TL;DR: In this article, the main emphasis was given on the anticancer activity of AG, its proposed mechanisms of action, novel approaches used to improve its biopharmaceutical properties, and its development as an adjuvant therapy for cancer treatment in future.

26 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

References
More filters
Journal ArticleDOI
10 Dec 2013-PLOS ONE
TL;DR: It can be concluded that the low-selectivity of AG in in vitro generated drug resistant and field isolated resistant strains was improved in case of AG nanomedicines designed with vitamin E TPGS.
Abstract: Visceral leishmaniasis (VL) is a chronic protozoan infection in humans associated with significant global morbidity and mortality. There is an urgent need to develop drugs and strategy that will improve therapeutic response for effective clinical treatment of drug resistant VL. To address this need, andrographolide (AG) nanoparticles were designed with P-gp efflux inhibitor vitamin E TPGS (D-α-tocopheryl polyethyleneglycol 1000 succinate) for sensitivity against drug resistant Leishmania strains. AG loaded PLGA (50∶50) nanoparticles (AGnps) stabilized by vitamin E TPGS were prepared for delivery into macrophage cells infested with sensitive and drug resistant amastigotes of Leishmania parasites. Physico-chemical characterization of AGnps by photon correlation spectroscopy exhibited an average particle size of 179.6 nm, polydispersity index of 0.245 and zeta potential of −37.6 mV. Atomic force microscopy and transmission electron microscopy visualization revealed spherical nanoparticles with smooth surfaces. AGnps displayed sustained AG release up to 288 hours as well as minimal particle aggregation and drug loss even after three months study period. Antileishmanial activity as revealed from selectivity index in wild-type strain was found to be significant for AGnp with TPGS in about one-tenth of the dosage of the free AG and one-third of the dosage of the AGnp without TPGS. Similar observations were also found in case of in vitro generated drug resistant and field isolated resistant strains of Leishmania. Cytotoxicity of AGnp with and without TPGS was significantly less than standard antileishmanial chemotherapeutics like amphotericin B, paromomycin or sodium stibogluconate. Macrophage uptake of AGnps was almost complete within one hour as evident from fluorescent microscopy studies. Thus, based on these observations, it can be concluded that the low-selectivity of AG in in vitro generated drug resistant and field isolated resistant strains was improved in case of AG nanomedicines designed with vitamin E TPGS.

40 citations


"Andrographolide engineered gold nan..." refers background in this paper

  • ...duces the desired effect without any toxic implications [27]....

    [...]

Journal ArticleDOI
M.P. Cava1, W.R. Chan1, L.J. Haynes1, L.F. Johnson1, B. Weinstein1 

37 citations


"Andrographolide engineered gold nan..." refers result in this paper

  • ...Presence of AG in AGAunp was further confirmed by conjugated C1⁄4C peak at 1674 cm 1 which corroborated with our previous report [41]....

    [...]

Journal ArticleDOI
TL;DR: Experimental OA nanoparticle formulation proved itself as an attractive carrier for OA which was significantly efficacious against both in vitro and in vivo amastigote form of Leishmania donovani than pure OA for chemotherapeutic intervention of visceral leishmaniasis.

30 citations


"Andrographolide engineered gold nan..." refers methods in this paper

  • ...The viable macrophage population was identified by trypan blue exclusion assay [25]....

    [...]

Journal ArticleDOI
01 Oct 2015
TL;DR: The biosynthesis of monodispersed GNPs using the spent cultures of Klebsiella pneumoniae as reducing and stabilizing agent has been reported and the gold salt concentration to improve monodispersity and stability of GNPs has been optimized.
Abstract: The development of eco-friendly approach for the preparation of monodispersed gold nanoparticles (GNPs) has received much attention for their easy application. Most of the current methods involve known protocols which employ toxic chemicals and hazardous byproducts. This greatly limits their use in biomedical fields, particularly in clinical applications. Recent research has been focused on green synthesis methods to produce different nanoparticles with suitable commercial viability. The biosynthesis of monodispersed GNPs using the spent cultures of Klebsiella pneumoniae as reducing and stabilizing agent has been reported. The gold salt concentration to improve monodispersity and stability of GNPs has been optimized. Synthesized GNPs were characterized by UV–Visible spectroscopy showed absorption spectra in the range of 530–560 nm at different concentrations of HAuCl4. At the optimum reaction concentration of 1.5 mM HAuCl4, absorption peak was obtained at 535 nm. The GNPs have been further characterized by X-ray diffraction, FTIR, DLS and TEM analysis. The DLS graph showed that the particles were more monodispersed. The TEM image showed the formation of spherical shaped GNPs in the range of 4–10 nm. The effect of gold salt concentration on dispersity, size and stability of the biosynthesized GNPs has been reported.

21 citations


"Andrographolide engineered gold nan..." refers methods in this paper

  • ...Single SPR spectra was recorded for all molar variations of HAuCl4: AG confirming the presence of spherical isotropic nano-scale population in accordance with Mie’s theory [38]....

    [...]

  • ...perse nature of the nano-gold population [38]....

    [...]