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: Research for leishmaniasis has been more and more focusing on the development of new tools such as diagnostic tests, drugs and vaccines, and the newly available control tools should allow a scaling up of control activities in priority areas.
Abstract: Leishmaniasis represents a complex of diseases with an important clinical and epidemiological diversity. Visceral leishmaniasis (VL) is of higher priority than cutaneous leishmaniasis (CL) as it is a fatal disease in the absence of treatment. Anthroponotic VL foci are of special concern as they are at the origin of frequent and deathly epidemics (e.g. Sudan). Leishmaniasis burden remains important: 88 countries, 350 million people at risk, 500,000 new cases of VL per year, 1-1.5 million for CL and DALYs: 2.4 millions. Most of the burden is concentrated on few countries which allows clear geographic priorities. Leishmaniasis is still an important public health problem due to not only environmental risk factors such as massive migrations, urbanisation, deforestation, new irrigation schemes, but also to individual risk factors: HIV, malnutrition, genetic, etc em leader Leishmaniasis is part of those diseases which still requires improved control tools. Consequently WHO/TDR research for leishmaniasis has been more and more focusing on the development of new tools such as diagnostic tests, drugs and vaccines. The ongoing effort has already produced significant results. The newly available control tools should allow a scaling up of control activities in priority areas. In anthroponotic foci, the feasibility of getting a strong impact on mortality, morbidity and transmission, is high.
2,150 citations
"Andrographolide engineered gold nan..." refers background in this paper
...infantum with a mortality rate of 50,000 per year [2]....
[...]
TL;DR: It is found that gold particles can be produced in a wide range of sizes, from 9 to 120 nm, with defined size distribution, following the earlier work of Turkevich and Frens.
Abstract: The growth of gold nanoparticles by reduction by citrate and ascorbic acid has been examined in detail to explore the parameter space of reaction conditions. It is found that gold particles can be produced in a wide range of sizes, from 9 to 120 nm, with defined size distribution, following the earlier work of Turkevich and Frens. The reaction is initiated thermally or in comparison by UV irradiation, which results in similar final products. The kinetics of the extinction spectra show the multiple steps of primary and secondary clustering leading to polycrystallites.
1,906 citations
TL;DR: It is observed that the slow rate of the reaction along with the shape directing effect of the constituents of the extract are responsible for the formation of single crystalline gold nanotriangles.
Abstract: Biogenic gold nanotriangles and spherical silver nanoparticles were synthesized by a simple procedure using Aloe vera leaf extract as the reducing agent. This procedure offers control over the size of the gold nanotriangle and thereby a handle to tune their optical properties, particularly the position of the longitudinal surface plasmon resonance. The kinetics of gold nanotriangle formation was followed by UV-vis-NIR absorption spectroscopy and transmission electron microscopy (TEM). The effect of reducing agent concentration in the reaction mixture on the yield and size of the gold nanotriangles was studied using transmission electron microscopy. Monitoring the formation of gold nanotriangles as a function of time using TEM reveals that multiply twinned particles (MTPs) play an important role in the formation of gold nanotriangles. It is observed that the slow rate of the reaction along with the shape directing effect of the constituents of the extract are responsible for the formation of single crystalline gold nanotriangles. Reduction of silver ions by Aloe vera extract however, led to the formation of spherical silver nanoparticles of 15.2 nm +/- 4.2 nm size.
1,801 citations
TL;DR: The methods of making nanoparticles using plant extracts are reviewed, methods of particle characterization are reviewed and potential applications of the particles in medicine are discussed.
1,706 citations
TL;DR: Millefosine, paromomycin and liposomal amphotericin B are gradually replacing pentavalent antimonials and conventional amphoteric in B as the preferred treatments in some regions, but in other areas these drugs are still being evaluated in both mono- and combination therapies.
Abstract: Visceral leishmaniasis (VL) is a systemic protozoan disease that is transmitted by phlebotomine sandflies. Poor and neglected populations in East Africa and the Indian sub-continent are particularly affected. Early and accurate diagnosis and treatment remain key components of VL control. In addition to improved diagnostic tests, accurate and simple tests are needed to identify treatment failures. Miltefosine, paromomycin and liposomal amphotericin B are gradually replacing pentavalent antimonials and conventional amphotericin B as the preferred treatments in some regions, but in other areas these drugs are still being evaluated in both mono- and combination therapies. New diagnostic tools and new treatment strategies will only have an impact if they are made widely available to patients.
1,463 citations
"Andrographolide engineered gold nan..." refers background in this paper
...donovani is prominent in all age groups [1] but its geographical spread is restricted to East Africa and India....
[...]