Antiviral Properties of Streptomyces tuirus DBZ39 Mediated Gold Nanoparticles Against Bluetongue virus.

<b>Background and Objective:</b> The proposed study involves the approach from the point of anti-viral activity of gold nanoparticles against the <i>Bluetongue virus</i>. Among viral diseases, Bluetongue is regarded as an economically scouring disease. Neither a vaccine nor an antiviral drug is available for the prevention or treatment of this disease. The antiviral activity of gold nanoparticles synthesized by a novel isolate of <i>Streptomyces tuirus</i> DBZ39 is the breakthrough of the study. <i>Streptomyces tuirus </i>DBZ39, a novel isolate obtained from alkaline soil was proved to be efficient actinomycetes, for the extracellular synthesis of gold nanoparticles. <b>Materials and Methods:</b> An upstream bioprocess was optimized and developed for the synthesis of controlled size gold nanoparticles with solitary mono dispersal pattern in aurum chloride solution. The characterization and confirmation of gold nanoparticles were illustrated by Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM), Energy Dispersive X-ray Analysis (EDAX) and Fourier Transmission Infrared Radiation Analysis (FTIR). <b>Results:</b> Biomass size of 3 g, substrate concentration of 1 mM, pH of 8.5 and temperature of 45°C were observed as optimum conditions for the synthesis of 15-24 nm size gold nanoparticles. The <i>Bluetongue virus</i> (BTV) which belongs to the genus Orbivirus in the family Reoviridae with 26 serotypes is an etiological agent of infectious and non-contagious Bluetongue disease of main sheep and several other domestic animals. <b>Conclusion:</b> Gold nanoparticles for the 1st time, at a higher concentration of 1:64 dilutions revealed a very promising and novel antiviral property against the <i>Bluetongue virus</i>.

Evaluation of the Physicochemical Properties of the Iron Nanoparticle Drug Products: Brand and Generic Sodium Ferric Gluconate.

Complex iron nanoparticle-based drugs are one of the oldest and most frequently administered classes of nanomedicines. In the US, there are seven FDA-approved iron nanoparticle reference drug products, of which one also has an approved generic drug product (i.e., sodium ferric gluconate (SFG)). These products are indicated for the treatment of iron deficiency anemia and are administered intravenously. On the molecular level, iron nanomedicines are colloids composed of an iron oxide core with a carbohydrate coating. This formulation makes nanomedicines more complex than conventional small molecule drugs. As such, these products are often referred to as nonbiological complex drugs (e.g., by the nonbiological complex drugs (NBCD) working group) or complex drug products (e.g., by the FDA). Herein, we report a comprehensive study of the physiochemical properties of the iron nanoparticle product SFG. SFG is the single drug for which both an innovator (Ferrlecit) and generic product are available in the US, allowing for comparative studies to be performed. Measurements focused on the iron core of SFG included optical spectroscopy, inductively coupled plasma mass spectrometry (ICP-MS), X-ray powder diffraction (XRPD), 57Fe Mössbauer spectroscopy, and X-ray absorbance spectroscopy (XAS). The analysis revealed similar ferric-iron-oxide structures. Measurements focused on the carbohydrate shell comprised of the gluconate ligands included forced acid degradation, dynamic light scattering (DLS), analytical ultracentrifugation (AUC), and gel permeation chromatography (GPC). Such analysis revealed differences in composition for the innovator versus the generic SFG. These studies have the potential to contribute to future quality assessment of iron complex products and will inform on a pharmacokinetic study of two therapeutically equivalent iron gluconate products.

Continued Efforts on Nanomaterial-Environmental Health and Safety Is Critical to Maintain Sustainable Growth of Nanoindustry.

Nanotechnology is enjoying an impressive growth and the global nanotechnology industry is expected to exceed US$ 125 billion by 2024. Based on these successes, there are notions that enough is known and efforts on engineered nanomaterial environmental health and safety (nano-EHS) research should be put on the back burner. However, there are recent events showing that it is not the case. The US Food and Drug Administration found ferumoxytol (carbohydrate-coated superparamagnetic iron oxide nanoparticle) for anemia treatment could induce lethal anaphylactic reactions. The European Union will categorize TiO2 as a category 2 carcinogen due to its inhalation hazard and France banned use of TiO2 (E171) in food from January 1, 2020 because of its carcinogenic potential. Although nanoindustry is seemingly in a healthy state, growth could be hindered for the lack of certainty and more nano-EHS research is needed for the sustainable growth of nanoindustry. Herein, the current knowledge gaps and the way forward are elaborated.

Design Considerations and Assays for Hemocompatibility of FDA-Approved Nanoparticles.

Nanoparticles have numerous biomedical applications including, but not limited to, targeted drug delivery, diagnostic imaging, sensors, and implants for a wide range of diseases including cancer, diabetes, heart disease, and tuberculosis. Although the mode of delivery of the nanoparticles depends on the application and the disease, the nanoparticles are often in immediate contact with the systemic circulation either because of intravenous administration or their ability to enter the bloodstream with relative ease or their longer survival time in circulation. Once in circulation, the nanoparticles may elicit unintended hemostatic and inflammatory responses, and hence the design of nanoparticles for therapeutic applications should take broad hemocompatibility concerns into consideration. In this review, we present the principles underlying the structural and functional design of various classes of nanoparticles that are currently approved by the US Food and Drug Administration, categorize these particles based on their interactions with cardiovascular tissues and ensuing adverse events, and also describe various in vitro assays that may be used evaluate their hemocompatibility.

Criteria to define a more relevant reference sample of titanium dioxide in the context of food: a multiscale approach.

Titanium dioxide (TiO2) is a transition metal oxide widely used as a white pigment in various applications, including food. Due to the classification of TiO2 nanoparticles by the International Agency for Research on Cancer as potentially harmful for humans by inhalation, the presence of nanoparticles in food products needed to be confirmed by a set of independent studies. Seven samples of food-grade TiO2 (E171) were extensively characterised for their size distribution, crystallinity and surface properties by the currently recommended methods. All investigated E171 samples contained a fraction of nanoparticles, however, below the threshold defining the labelling of nanomaterial. On the basis of these results and a statistical analysis, E171 food-grade TiO2 totally differs from the reference material P25, confirming the few published data on this kind of particle. Therefore, the reference material P25 does not appear to be the most suitable model to study the fate of food-grade TiO2 in the gastrointestinal tract. The criteria currently to obtain a representative food-grade sample of TiO2 are the following: (1) crystalline-phase anatase, (2) a powder with an isoelectric point very close to 4.1, (3) a fraction of nanoparticles comprised between 15% and 45%, and (4) a low specific surface area around 10 m2 g-1.

PVP- coated naringenin nanoparticles for biomedical applications - In vivo toxicological evaluations.

Naringenin (NAR) is one of the naturally occurring flavonoids found in citrus fruits and exerts a wide variety of pharmacological activities. The clinical relevance of naringenin is limited by its low solubility and minimal bioavailability, owing to its largely hydrophobic ring structure. The aim of the present study is to develop a novel naringenin nanoparticle system (NAR NP) using simple nanoprecipitation technique with polyvinylpyrrolidone (PVP) as the hydrophilic carrier. The synthesized nanoparticles were characterized using XRD, FTIR, SEM and EDX. The characterization study revealed the nanoscale properties and the interactions between NAR and PVP. In vivo toxicological evaluations were carried out at various doses (1, 5, 10 & 50 mg/kg body wt) in male Sprague-Dawley rats in comparison with silver nanoparticle (AgNP) at toxic concentration (50 mg/kg body wt). The altered hepatotoxicity markers, hematology parameters and antioxidant defense system were observed in AgNP- treated rats. But NAR NP - treated rats did not show any biochemical alterations and improved the antioxidant defense indices when compared to control group, by virtue of the pharmacological properties exerted by NAR. The modulatory effect of NAR NP over inflammatory and stress signaling cascades were confirmed by the normalized mRNA expressions of NF-κB, TNF-α and IL-6. The histopathological analysis of liver, kidney and heart reinforce our findings. These studies provide preliminary answers to some of the key biological issues raised over the use and safety of nanoparticles for diagnostic and therapeutic applications. Consequently, we suggest that the safe NAR NP can be used to reduce the dosage of NAR, improve its bioavailability and merits further investigation for therapeutic applications.

In vivo evaluation of the efficacy of albendazole sulfoxide and albendazole sulfoxide loaded solid lipid nanoparticles against hydatid cyst.

Cystic echinococcosis (CE) is caused by the larval stage of Echinococcus granulosus, which in this disease the metacestode develop in visceral organs especially liver and lungs. The disease is present worldwide and affects humans as well as herbivores including cattle, sheep, camels, horses and others. Benzimidazole carbamate derivatives, such as mebendazole and albendazole, are currently used for chemotherapeutic treatment of CE in inoperable patients and have to be applied in high doses for extended periods of time, and therefore adverse side effects are frequently observed. This study was designed to evaluate and compare the in vivo effects of 0.5 mg/kg, BID, albendazole sulfoxide (ricobendazole) and two different therapeutic regimens of 0.5 mg/kg BID and 2 mg/kg every 48 h of albendazole sulfoxide loaded solid lipid nanoparticles. Albendazole sulfoxide loaded solid lipid nanoparticles was prepared by solvent diffusion-evaporation method. Fifty Balb/c mice were infected by intraperitoneal injection of protoscoleces and 8 months post infection, the infected mice were treated for 15 days with the above mentioned regimens. They were then euthanized and the size and weight of the cysts as well as their ultrastructural changes were investigated. Although the cysts showed reduced size and weight in the treated animals but these reductions were not statistically significant. The cysts in the animals which received albendazole sulfoxide loaded SLN every 48 h showed more ultrastructural modification. However, these ultrastructural changes should be supported by further biochemical and molecular studies before introducing it as an efficient therapeutic regimen for treatment of human and animal hydatid disease.

Nano in cancer: linking chemistry, biology, and clinical applications in vivo.

Development of nanoparticle agents for cancer therapeutics and diagnostics is steadily progressing and was the subject of the inaugural conference entitled, "Nano in Cancer," held during January 12-15, 2011, in Miami, FL. The meeting program was developed by co-chairs David Piwnica-Worms (Washington University in St. Louis), Jan Schnitzer (Proteogenomics Research Institute for Systems Medicine, San Diego), and Karen Wooley (Texas A&M University). Topics discussed for nanoparticle platforms under development included: nanotechnologies for cancer diagnostics and imaging, overcoming in vivo barriers, therapeutic nanoparticles and clinical prospects, and safety issues for nanotechnologies. Two important concepts emerged from this meeting. The first was the urgent need for uniform standards and protocols for nanoparticle characterization in vitro and in vivo, and the second was the continued need for discovery of definitive targets for tumor-directed nanoparticles across various cancers.

Design and influence of gamma-irradiation on the biopharmaceutical properties of nanoparticles containing an antigenic complex from Brucella ovis.

Despite vaccination campaigns, brucellosis is still one of the most common bacterial zoonosis in the world. This work describes the development of a novel formulation strategy to the delivery of the Brucella ovis antigenic extract (HS) into ovine mucosal surfaces. Thus, HS was entrapped in conventional and mannosylated poly(anhydride) nanoparticles by the solvent displacement method, and the resulting nanosystems were gamma-irradiated to accomplish the sterilization required for the ophthalmic administration route. Sterilization, at either 10 kGy or 25 kGy, did not modify the size, morphology and antigen content of the nanoparticles. Similarly, the integrity and antigenicity of the entrapped antigen were not affected by gamma-irradiation. The 25 kGy gamma-irradiation dose seemed to influence negatively the HS release from the carriers. However, and in accordance with the Pearson's correlation, all the release patterns followed a similar tendency. Furthermore, the stability of the vaccine systems on lachrymal and nasal ovine fluids, showed that gamma-irradiation had no significant effects on the vaccine systems. Since all the vaccine systems accomplished the pharmacopoeial biological tests required for gamma-irradiation doses under 25 kGy, these results are highly suggestive for the use of HS loaded poly(anhydride) nanoparticles as an efficient vaccine delivery system for brucellosis immunoprophylaxis, especially for ophthalmic administration.

Migration, fate and in vivo imaging of adult stem cells in the CNS.

Adult stem cells have been intensively studied for their potential use in cell therapies for neurodegenerative diseases, ischemia and traumatic injuries. One of the most promising cell sources for autologous cell transplantation is bone marrow, containing a heterogenous cell population that can be roughly divided into hematopoietic stem and progenitor cells and mesenchymal stem cells (MSCs). MSCs are multipotent progenitor cells that, in the case of severe tissue ischemia or damage, can be attracted to the lesion site, where they can secrete bioactive molecules, either naturally or through genetic engineering. They can also serve as vehicles for delivering therapeutic agents. Mobilized from the marrow, sorted or expanded in culture, MSCs can be delivered to the damaged site by direct or systemic application. In addition, MSCs can be labeled with superparamagnetic nanoparticles that allow in vivo cell imaging. Magnetic resonance imaging (MRI) is thus a suitable method for in vivo cell tracking of transplanted cells in the host organism. This review will focus on cell labeling for MRI and the use of MSCs in experimental and clinical studies for the treatment of brain and spinal cord injuries.