Andrographolide engineered gold nanoparticle to overcome drug resistant visceral leishmaniasis.
08 Feb 2018-Artificial Cells Nanomedicine and Biotechnology (Artif Cells Nanomed Biotechnol)-Vol. 46, pp 751-762
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
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) *** *** *** *** ***...
[...]
Chinese Ministry of Education1, Shanghai University2, Nanjing University of Chinese Medicine3, Beijing University of Chinese Medicine4, Tianjin University of Traditional Chinese Medicine5, Chengdu University of Traditional Chinese Medicine6, Chinese Academy of Sciences7, China Pharmaceutical University8, Guangzhou University of Chinese Medicine9, Guizhou University10, Fujian University of Traditional Chinese Medicine11, Fudan University12, Yale University13, Peking University14, Zhejiang University15
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
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
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
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
TL;DR: It is demonstrated that the well-established endosomal route of cellular uptake can be bypassed to a significant extent by controlling the uptake mechanism either via the delivery of the nanoparticles by liposomes or by surface modification ofThe nanoparticles with so-called cell penetrating peptides (CPPs).
Abstract: Understanding and controlling the interactions between nanoscale objects and living cells is of great importance for arising diagnostic and therapeutic applications of nanoparticles and for nanotoxicology studies. Here we report a detailed transmission electron microscopy (TEM) study of the uptake of ca. 16 nm surface-modified gold nanoparticles by human fibroblast cells (HeLa cells). It is demonstrated that the well-established endosomal route of cellular uptake can be bypassed to a significant extent by controlling the uptake mechanism either via the delivery of the nanoparticles by liposomes or by surface modification of the nanoparticles with so-called cell penetrating peptides (CPPs). Successful nuclear targeting is demonstrated using surface modification with a cocktail of CPPs and a peptide acting as a nuclear localization signal (NLS).
619 citations
TL;DR: Hydroquinone can be used to produce 50-200 nm gold nanoparticles that are relatively monodispersed in size with nearly spherical shapes that contribute to nanotoxicology and biomedicine.
Abstract: Elucidating the impact of nanoparticle size and shape on biological systems is of fundamental importance to nanotoxicology and biomedicine. Currently, the ability to determine this is limited by the lack of a model nanoparticle system having a narrow size and shape distribution over the relevant size range (2−200 nm). Hydroquinone can be used to produce 50−200 nm gold nanoparticles that are relatively monodispersed in size with nearly spherical shapes.
591 citations
TL;DR: This tutorial review will highlight some of the many forms and recent applications of these gold nanoparticle conjugates by the lab and others, as well as their rational design and physiologic interactions.
Abstract: Gold nanoparticles possess a unique combination of properties which allow them to act as highly multifunctional anti-cancer agents (X. H. Huang, P. K. Jain, I. H. El-Sayed and M. A. El-Sayed, Nanomedicine, 2007, 2, 681-693; P. Ghosh, G. Han, M. De, C. K. Kim and V. M. Rotello, Adv. Drug Delivery Rev., 2008, 60, 1307-1315; S. Lal, S. E. Clare and N. J. Halas, Acc. Chem. Res., 2008, 41, 1842-1851; D. A. Giljohann, D. S. Seferos, W. L. Daniel, M. D. Massich, P. C. Patel and C. A. Mirkin, Angew. Chem., Int. Ed., 2010, 49, 3280-3294). Not only can they be used as targeted contrast agents for photothermal cancer therapy, they can serve as scaffolds for increasingly potent cancer drug delivery, as transfection agents for selective gene therapy, and as intrinsic antineoplastic agents. This tutorial review will highlight some of the many forms and recent applications of these gold nanoparticle conjugates by our lab and others, as well as their rational design and physiologic interactions.
555 citations
"Andrographolide engineered gold nan..." refers background in this paper
...Nanoscale gold with its distinctive features like functional versatility, biocompatibility, low/non-toxicity and adjustability in size/shape is ideal for application in therapy and detection [8]....
[...]
TL;DR: The different approaches to lead discovery for tropical diseases are discussed and a coordination strategy that involves highly integrated partnerships and networks between scientists in academic institutions and industry in both wealthy industrialized countries and disease-endemic countries is emphasized.
Abstract: Lead discovery is currently a key bottleneck in the pipeline for much-needed novel drugs for tropical diseases such as malaria, tuberculosis, African sleeping sickness, leishmaniasis and Chagas disease. Here, we discuss the different approaches to lead discovery for tropical diseases and emphasize a coordination strategy that involves highly integrated partnerships and networks between scientists in academic institutions and industry in both wealthy industrialized countries and disease-endemic countries. This strategy offers the promise of reducing the inherently high attrition rate of the early stages of discovery research, thereby increasing the chances of success and enhancing cost-effectiveness.
496 citations
"Andrographolide engineered gold nan..." refers background in this paper
...edged to have promising activity [28] for further evaluations....
[...]
TL;DR: Gold nanorods were taken up to a lesser extent by the liver, had longer circulation time in the blood, and higher accumulation in the tumors, compared with their spherical counterparts.
456 citations
"Andrographolide engineered gold nan..." refers background in this paper
...Similarly, nano-scale gold with negative surface charge like AGAunp exhibits improved macrophage internalization than those with neutral surface charge but of the same size as scavenger receptors exhibits preferential recognition of anionic sites [49]....
[...]