Gold nanoparticles as a promising treatment for diabetes and its complications: Current and future potentials

Diabetes and its complications represent a major cause of morbidity and mortality in diabetes patients. This review is aimed to find the potential of gold nanoparticles (AuNPs) to act as therapeutic agents for diabetes and its complications. Here, we outline the literature related to the self-therapeutic effects of AuNPs. The first goal of this review is to highlight and summarize some of the existing studies (10 years ago) in terms of several parameters such as the size of AuNPs, dose, administration route, experimental model, experimental analysis, and findings. The second goal is to describe the self-therapeutic effects of AuNPs against the pathogenesis determinants of diabetic complications. AuNPs have been found to have inhibitory effects on transforming growth factor-ß, antiglycation, antiangiogenic, anti-hyperglycemic, anti-inflammatory, and antioxidant effects. AuNPs treatment effectively disrupts multiple pathogenesis determinants in an animal model of diabetes and diabetic complications. The present review provides insight into the potential applications of AuNPs, which may help reduce the incidence of diabetes and its complications

Nanocristais de flubendazol: preparação e caracterização físico-química / Flubendazole nanocrystals: preparation and physical-chemical characterization

Os nanocristais são partículas de fármacos cristalinos, com tamanho médio na faixa de submicrons, geralmente entre 200 e 500 nm, estabilizados por agentes estéricos ou eletrostáticos adsorvidos na superfície das partículas do fármaco. Sua dimensão reduzida proporciona propriedades especiais, como a adesividade às mucosas e o aumento de área superficial e da solubilidade de saturação, o que melhora significativamente a biodisponibilidade de fármacos pouco solúveis em água. Outra aplicação emergente dos nanocristais é na melhoria da entrega e da retenção de fármacos em tecidos e células tumorais. Estudos demonstraram que o flubendazol é um fármaco capaz de induzir a morte celular em tumores malignos e retardar o seu crescimento, por meio da alteração que provoca na estrutura dos microtúbulos e pela inibição da polimerização da tubulina. Foi demonstrada sua atividade antiproliferativa em linhagens de leucemia, mieloma, câncer intestinal, câncer de mama e neuroblastoma. O flubendazol é também um fármaco eficaz contra os helmintos, demonstrando atividade superior na eliminação dos vermes adultos, quando comparado com a dietilcarbamazina. Embora o flubendazol pareça ser uma molécula promissora, é um fármaco praticamente insolúvel em água (0,005 mg/mL). Para atingir o efeito terapêutico desejado, é necessário o desenvolvimento de uma formulação com melhores solubilidade e biodisponibilidade. Nesse sentido, o presente trabalho apresenta o preparo e a caracterização físico-química de nanocristais de flubendazol por meio da microfluidização. Foram realizados ensaios exploratórios para avaliar a performance de diferentes agentes estabilizantes nas suspensões: o polissorbato 80, o polaxamer 188 e o D-α tocoferol polietilenoglicol 1.000 succinato (TPGS). A avaliação da distribuição do tamanho de partícula foi realizada por espalhamento de luz laser (LLS), espalhamento de luz dinâmica (DLS), análise de rastreamento de nanopartículas (NTA) e microscopia eletrônica de varredura (MEV). A utilização do TPGS favoreceu a obtenção de uma nanossuspensão com o menor diâmetro hidrodinâmico médio das partículas, de 253,9 ± 3,0 nm. Nos estudos exploratórios, também foram determinados os parâmetros ótimos de moagem do microfluidizador, sendo estabelecidos: 35.000 psi de pressão, temperatura do produto de 30°C (± 5°C) e tempo de recirculação de 2 horas/100 gramas. Objetivando alcançar o menor diâmetro hidrodinâmico médio dos nanocristais, executou-se um planejamento estatístico no qual foi avaliada a influência da concentração de flubendazol (% p/p) e de TPGS (% p/p) na formulação. A análise revelou a significativa influência da concentração do TPGS na redução do tamanho de partícula e na estabilidade físico-química da nanossuspensão. Ensaios complementares de solubilidade demonstraram que o nanocristal proporcionou incremento na solubilidade de 2,3 e 3,2 e 5,2 vezes em HCl 0,1 N, tampão fosfato pH 6,8 e tampão fosfato salino pH 7,4, respectivamente. No ensaio de dissolução conduzido em HCl 0,1 N e 0,1% TPGS, observou-se significativo incremento, de 41% de fármaco dissolvido após 60 minutos, quando comparado com o flubendazol micronizado. As características do estado sólido do nanocristal foram avaliadas por meio de análise térmica (calorimetria exploratória diferencial e termogravimetria) e difratometria de raios X, não sendo observadas significativas alterações da estrutura cristalina. O presente trabalho também avaliou a efetividade dos nanocristais de flubendazol em tumores de pulmão, demonstrando sua expressiva capacidade de retardar o crescimento e diminuir o tamanho desses tumores em camundongos xenotransplantados

Os nanocristais são partículas de fármacos cristalinos, com tamanho médio na faixa de submicrons, geralmente entre 200 e 500 nm, estabilizados por agentes estéricos ou eletrostáticos adsorvidos na superfície das partículas do fármaco. Sua dimensão reduzida proporciona propriedades especiais, como a adesividade às mucosas e o aumento de área superficial e da solubilidade de saturação, o que melhora significativamente a biodisponibilidade de fármacos pouco solúveis em água. Outra aplicação emergente dos nanocristais é na melhoria da entrega e da retenção de fármacos em tecidos e células tumorais. Estudos demonstraram que o flubendazol é um fármaco capaz de induzir a morte celular em tumores malignos e retardar o seu crescimento, por meio da alteração que provoca na estrutura dos microtúbulos e pela inibição da polimerização da tubulina. Foi demonstrada sua atividade antiproliferativa em linhagens de leucemia, mieloma, câncer intestinal, câncer de mama e neuroblastoma. O flubendazol é também um fármaco eficaz contra os helmintos, demonstrando atividade superior na eliminação dos vermes adultos, quando comparado com a dietilcarbamazina. Embora o flubendazol pareça ser uma molécula promissora, é um fármaco praticamente insolúvel em água (0,005 mg/mL). Para atingir o efeito terapêutico desejado, é necessário o desenvolvimento de uma formulação com melhores solubilidade e biodisponibilidade. Nesse sentido, o presente trabalho apresenta o preparo e a caracterização físico-química de nanocristais de flubendazol por meio da microfluidização. Foram realizados ensaios exploratórios para avaliar a performance de diferentes agentes estabilizantes nas suspensões: o polissorbato 80, o polaxamer 188 e o D-α tocoferol polietilenoglicol 1.000 succinato (TPGS). A avaliação da distribuição do tamanho de partícula foi realizada por espalhamento de luz laser (LLS), espalhamento de luz dinâmica (DLS), análise de rastreamento de nanopartículas (NTA) e microscopia eletrônica de varredura (MEV). A utilização do TPGS favoreceu a obtenção de uma nanossuspensão com o menor diâmetro hidrodinâmico médio das partículas, de 253,9 ± 3,0 nm. Nos estudos exploratórios, também foram determinados os parâmetros ótimos de moagem do microfluidizador, sendo estabelecidos: 35.000 psi de pressão, temperatura do produto de 30°C (± 5°C) e tempo de recirculação de 2 horas/100 gramas. Objetivando alcançar o menor diâmetro hidrodinâmico médio dos nanocristais, executou-se um planejamento estatístico no qual foi avaliada a influência da concentração de flubendazol (% p/p) e de TPGS (% p/p) na formulação. A análise revelou a significativa influência da concentração do TPGS na redução do tamanho de partícula e na estabilidade físico-química da nanossuspensão. Ensaios complementares de solubilidade demonstraram que o nanocristal proporcionou incremento na solubilidade de 2,3 e 3,2 e 5,2 vezes em HCl 0,1 N, tampão fosfato pH 6,8 e tampão fosfato salino pH 7,4, respectivamente. No ensaio de dissolução conduzido em HCl 0,1 N e 0,1% TPGS, observou-se significativo incremento, de 41% de fármaco dissolvido após 60 minutos, quando comparado com o flubendazol micronizado. As características do estado sólido do nanocristal foram avaliadas por meio de análise térmica (calorimetria exploratória diferencial e termogravimetria) e difratometria de raios X, não sendo observadas significativas alterações da estrutura cristalina. O presente trabalho também avaliou a efetividade dos nanocristais de flubendazol em tumores de pulmão, demonstrando sua expressiva capacidade de retardar o crescimento e diminuir o tamanho desses tumores em camundongos xenotransplantados

Biosynthesis of gold nanoparticles by two bacterial and fungal strains, Bacillus cereus and Fusarium oxysporum, and assessment and comparison of their nanotoxicity in vitro by direct and indirect assays

Background: Although nanoparticles (NPs) have many advantages, it has been proved that they may be absorbed by and have toxic effects on the human body. Recent research has tried to evaluate and compare the nanotoxicity of gold nanoparticles (AuNPs) produced by two types of microorganisms in vitro by two different methods. AuNPs were produced by Bacillus cereus and Fusarium oxysporum, and their production was confirmed by visible spectral, transmission electron microscope, and X-ray diffraction (XRD) analyses. The human fibroblast cell line CIRC-HLF was treated with AuNPs, and the induced nanotoxicity was measured using direct microscopic and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. Results: The results showed that the produced AuNPs had a maximum absorbance peak around 510­530 nanometer (nm), with spherical, hexagonal, and octagonal shapes and average sizes around 20­50 nm. The XRD results confirmed the presence of GNPs in the microbial culture supernatants. An MTT assay showed that GNPs had dose-dependent toxic effects, and microscopic analysis showed that GNPs induced cell abnormalities in doses lower than the determined half-maximal inhibitory concentrations (IC50s). Conclusions: In conclusion, the biologically produced AuNPs had toxic effects in the cell culture, and direct techniques such as microscopic evaluation instead of indirect methods such as MTT assay were more useful for assessing the nanotoxicity of the biologically produced AuNPs. Thus, the use of only MTT assay for nanotoxicity evaluation of AuNPs is not desirable.

Cobalt oxide nanoparticles aggravate DNA damage and cell death in eggplant via mitochondrial swelling and NO signaling pathway

BACKGROUND: Despite manifold benefits of nanoparticles (NPs), less information on the risks of NPs to human health and environment has been studied. Cobalt oxide nanoparticles (Co3O4-NPs) have been reported to cause toxicity in several organisms. In this study, we have investigated the role of Co3O4-NPs in inducing phytotoxicity, cellular DNA damage and apoptosis in eggplant (Solanum melongena L. cv. Violetta lunga 2). To the best of our knowledge, this is the first report on Co3O4-NPs showing phytotoxicity in eggplant. RESULTS: The data revealed that eggplant seeds treated with Co3O4-NPs for 2 h at a concentration of 1.0 mg/ml retarded root length by 81.5 % upon 7 days incubation in a moist chamber. Ultrastructural analysis by transmission electron microscopy (TEM) demonstrated the uptake and translocation of Co3O4-NPs into the cytoplasm. Intracellular presence of Co3O4-NPs triggered subcellular changes such as degeneration of mitochondrial cristae, abundance of peroxisomes and excessive vacuolization. Flow cytometric analysis of Co3O4-NPs (1.0 mg/ml) treated root protoplasts revealed 157, 282 and 178 % increase in reactive oxygen species (ROS), membrane potential (APm) and nitric oxide (NO), respectively. Besides, the esterase activity in treated protoplasts was also found compromised. About 2.4-fold greater level of DNA damage, as compared to untreated control was observed in Comet assay, and 73.2 % of Co3O4-NPs treated cells appeared apoptotic in flow cytometry based cell cycle analysis. CONCLUSION: This study demonstrate the phytotoxic potential of Co3O4-NPs in terms of reduction in seed germination, root growth, greater level of DNA and mitochondrial damage, oxidative stress and cell death in eggplant. The data generated from this study will provide a strong background to draw attention on Co3O4-NPs environmental hazards to vegetable crops.

Antibacterial properties of silver nanoparticles synthesized by marine Ochrobactrum sp.

Metal nanoparticle synthesis is an interesting area in nanotechnology due to their remarkable optical, magnetic, electrical, catalytic and biomedical properties, but there needs to develop clean, non-toxic and environmental friendly methods for the synthesis and assembly of nanoparticles. Biological agents in the form of microbes have emerged up as efficient candidates for nanoparticle synthesis due to their extreme versatility to synthesize diverse nanoparticles with varying size and shape. In the present study, an eco favorable method for the biosynthesis of silver nanoparticles using marine bacterial isolate has been attempted. Very interestingly, molecular identification proved it as a strain of Ochrobactrum anhtropi. In addition, the isolate was found to have the potential to form silver nanoparticles intracellularly at room temperature within 24 h. The biosynthesized silver nanoparticles were characterized by UV-Vis spectroscopy, transmission electron microscope (TEM) and scanning electron microscope (SEM). The UV-visible spectrum of the aqueous medium containing silver nanoparticles showed a peak at 450 nm corresponding to the plasmon absorbance of silver nanoparticles. The SEM and TEM micrographs revealed that the synthesized silver nanoparticles were spherical in shape with a size range from 38 nm - 85 nm. The silver nanoparticles synthesized by the isolate were also used to explore its antibacterial potential against pathogens like Salmonella Typhi, Salmonella Paratyphi, Vibrio cholerae and Staphylococcus aureus.

Green Synthesis of AgNPs Stabilized with biowaste and their antimicrobial activities

In the present study, rapid reduction and stabilization of Ag+ ions with different NaOH molar concentration (0.5 mM, 1.0 mM and 1.5 mM) has been carried out in the aqueous solution of silver nitrate by the bio waste peel extract of P.granatum. Generally, chemical methods used for the synthesis of AgNPs are quite toxic, flammable and have adverse effect in medical application but green synthesis is a better option due to eco-friendliness, non-toxicity and safe for human. Stable AgNPs were synthesized by treating 90 mL aqueous solution of 2 mM AgNO3 with the 5 mL plant peels extract (0.4% w/v) at different NaOH concentration (5 mL). The synthesized AgNPs were characterized by UV-Vis spectroscopy, TEM and SEM. Further, antimicrobial activities of AgNPs were performed on Gram positive i.e. Staphylococcus aureus, Bacillus subtilius and Gram negative i.e. E. coli, Pseudomonas aeruginosa bacteria. The AgNPs synthesized at 1.5 mM NaOH concentration had shown maximum zone of inhibition (ZOI) i.e. 49 ± 0.64 in E. coli, whereas Pseudomonas aeruginosa, Staphylococcus aureus and Bacillus subtilius had shown 40 ± 0.29 mm, 28 ± 0.13 and 42 ± 0.49 mm ZOI respectively. The MIC value of 30 g/mL observed for E. coli Whereas, Staphylococcus aureus, Bacillus subtilius and Pseudomonas aeruginosa had shown 45 µg/mL, 38 µg/mL, 35 µg/mL respectively. The study revealed that AgNPs had shown significant antimicrobial activity as compared to Streptomycin.

Microbial mediated preparation, characterization and optimization of gold nanoparticles

The need for eco-friendly and cost effective methods for nanoparticles synthesis is developing interest in biological approaches which are free from the use of toxic chemicals as byproducts. This study aimed to biosynthesize and optimize the size of gold nanoparticles which produced by biotechnological method using Penicillium crustosum isolated from soil. Initially, Penicillium crustosum was grown in fluid czapek dox broth on shaker at 28 ºC and 200 rpm for ten days and then the supernatant was separated from the mycelia to convert AuCl4 solution into gold nanoparticles. The synthesized nanoparticles in the optimum conditions were formed with fairly well-defined dimensions and good monodispersity. The characterizations were done by using different methods (UV-Visible Spectroscopy, Fluorescence, FT-IR, AFM (Atomic Force Microscopy) and DLS (Dynamic Light Scattering). The bioconversion was optimized by Box-Behnken experimental design. The results show that the effective factors in this process were concentration of AuCl4, pH of medium and temperature of shaker incubator. The R² value was calculated to be 0.9999 indicating the accuracy and ability of the polynomial model. It can be concluded that the use of multivariate analysis facilitated to find out the optimum conditions for the biosynthesis of gold nanoparticles induced by Penicillium crustosum in a time and cost effective process. The current approach suggested that rapid synthesis of gold nanoparticles would be suitable for developing a biological process for mass scale production of formulations.

Bionanoparticles, a green nanochemistry approach

Background: In the past decade, considerable attention has been paid for the development of novel strategies for the synthesis of different kind of nano-objects. Most of the current strategies are usually working by the use physical or chemical principles to develop a myriad of nano-objects with multiple applications. Main fields of nanotechnology applications range from catalysis, micro- and nano-electronics (semiconductors, single electrons transistors), non-linear optic devices, photo-electrochemistry to biomedicine, diagnostics, foods and environment, chemical analysis and others. Results: Two main avenues for nanoparticles synthesis: cell-free extract and cell cultivation have been reported. The state of art of both biotechnological approaches for different type nanoparticles are reviewed in this work. Conclusions: Nanotechnology is a revolutionary field just at its onset, the trend in the next decades being its integration with the green chemistry approach. Several strategies involving exhaustive strain selection, cultivation modes, recombinant gene expression, metabolic engineering, protein re-design and re-engineering, and predictive modeling will allow to create nanobioreactors, a new nanobiotechnology arena with a high potential impact in many fields.

Distribution and accumulation of Cy5.5-labeled thermally cross-linked superparamagnetic iron oxide nanoparticles in the tissues of ICR mice

Free Cy5.5 dye and Cy5.5-labeled thermally cross-linked superparamagnetic iron oxide nanoparticles (TCL-SPION) have been routinely used for in vivo optical imaging. However, there is little information about the distribution and accumulation of free Cy5.5 dye and Cy5.5-labeled TCL-SPION in the tissues of mice. Free Cy5.5 dye (0.1 mg/kg body weight) and Cy5.5-labeled TCL-SPION (15 mg/kg body weight) were intravenously injected into the tail vein of ICR mice. The biodistribution and accumulation of the TCL-SPION and Cy5.5 were observed by ex vivo optical imaging and fluorescence signal generation at various time points over 28 days. Cy5.5 dye fluorescence in various organs was rapidly eliminated from 0.5 to 24 h post-injection. Fluorescence intensity of Cy5.5 dye in the liver, lung, kidney, and stomach was fairly strong at the early time points within 1 day post-injection. Cy5.5-labeled TCL-SPION had the highest fluorescence density in the lung at 0.5 h post-injection and decreased rapidly over time. Fluorescence density in liver and spleen was maintained over 28 days. These results suggest that TCL-SPION can be useful as a carrier of therapeutic reagents to treat diseases by persisting for long periods of time in the body.