Any drug intended for systemic administration and all medical devices which will contact blood must undergo thorough biocompatibility testing. These tests include an in vitro assay to determine the material's potential to damage red blood cells (hemolysis). Hemolysis, the abnormal breakdown of red blood cells either in the blood vessels (intravascular hemolysis) or elsewhere in the body (extravascular), can lead to anemia or other pathological conditions. In the pharmaceutical industry, hematocompatibility testing is harmonized through the use of internationally recognized standard protocols. Nanotechnology- based medical devices and drug carriers are emerging as alternatives to conventional small-molecule drugs, and in vitro evaluation of their biocompatibility with blood components is a necessary part of early preclinical development. Many research papers have reported nanoparticle hemolytic properties but, so far, no in vitro hemolysis protocol has been available that is specific to nanoparticles. A new study published this month describes in vitro assays to study nanoparticle hemolytic properties, identifies nanoparticle interferences with these in vitro tests and provides the first comprehensive insight to potential sources of this interference, demonstrates the usefulness of including nanoparticle-only controls, and illustrates the importance of physicochemical characterization of nanoparticle formulations and visually monitoring test samples to avoid false-positive or false-negative results.
Nanoparticles with at least one dimension of 100 nanometers or less fall in the transitional zone between individual atoms or molecules and the corresponding bulk material, which can drastically modify the physicochemical properties of the material and may generate adverse biological effects in organisms. As the discussion about potentially undesired side effects of engineered nanoparticles heats up, research on toxicological effects of nanomaterials gets increasing attention. Nanotoxicology is quickly being established as a new field, with its major focus on human and animal studies. However, very few studies have been conducted to assess the toxicity of nanomaterials to ecological terrestrial species, particularly plants. So far, the mechanisms of nanoparticle phytotoxicity ? the ability to cause injury to plants ? remain largely unknown and little information on the potential uptake of nanoparticles by plants and their subsequent fate within the food chain is available.
Engineered nanoparticles are rapidly becoming a part of our daily life in the form of cosmetics, food packaging, drug delivery systems, therapeutics, biosensors, etc. A number of commercial products such as wound dressing, detergents or antimicrobial coatings are already in the market. Although little is known about their bio distribution and bio activity, especially silver nanoparticles are extensively used for all kinds of antimicrobial applications. Ultimately, these nanoparticles end up in the environment during waste disposal. Largely due to a scarcity of data on the toxicity, intracellular distribution and fate of silver ions and nanoparticles inside an organism, regulatory bodies so far have not felt the need to regulate the use of such materials in commercial products or disposal of such products. In order to improve the scientific data and to enhance our insight on the health and environmental impact of silver nanoparticles, scientists in Singapore have initiated an in vivo toxicology study to examine nanosilver in a zebrafish model. They conclude that silver nanoparticles have the potential to cause health and ecotoxicity issues in a concentration-dependent manner.
Germany, with an almost 40% share of European public funded nanoscience research, is the clear nanotechnology leader in Europe. It is also one of the leaders globally in pushing research into potential risk and safety concerns associated with nanotechnology. The Federal Ministry of Education and Research (BMBF) is the ministry responsible for federal activities in the nanotechnology sector in Germany. Within its framework of 'leading-edge innovations' the BMBF supports key areas of nanotechnologies with promising prospects (NanoMobil, NanoChem, NanoFab, NanoforLife,NanoLux). The project NanoChance aims to support small and medium-sized companies in particular. The cooperative project NanoCare currently mainly focuses on studying possible risks of engineered nanoparticles. Beyond that, the federal agencies BAuA (Federal Institute for Occupational Safety and Health), UBA (Federal Environment Agency) and BfR (Federal Institute for Risk Assessment) have developed a joint research strategy that addresses especially health and environmental risks of engineered nanoparticles. The strategy has been finalized in December 2007 and a final report has just been published.
High content analysis (HCA) is a powerful platform that combines cell-based assays with traditional microscopy and automated, sophisticated image processing and analysis software. This technology is capable of using living and fixed cells, typically with fluorescently labeled antibodies and reagents. It has been widely adopted in the pharmaceutical and biotechnology industries for target identification and validation. HCA has made particular inroads into research and development applications where high throughput screening has proven inadequate, such as measuring multiple biological pathways simultaneously, or revealing off-target drug effects. HCA has stepped into this void by demonstrating how particular proteins are affected by the application of a molecule to the cell line of interest.
Synthesized carbon nanotubes, especially single-walled carbon nanotubes (SWCNTs), are in the form of bundles with other impurities such as catalyst particles and amorphous carbon debris. In order to be useful for many types of applications, for instance in nanoelectronic devices or biomedical applications, SWCNTs need to be purified and dispersed into individual nanotubes. One method to do this is by surfactant stabilization of the hydrophobic nanotube surface, which overcomes the van der Waals forces among the nanotubes and results in suspensions of individual SWCNTs. Researchers have now investigated the cytotoxicity of SWCNTs suspended in various surfactants. Their experimental results show that the conjugates SDS/CNT and SDBS/CNT are toxic to astrocytoma cells due solely to the toxicity of the SDS and SDBS molecules, which administered alone are toxic to the cells even at a low concentration of 0.05 mg per ml within 30 min. However, the proliferation and viability of the astrocytoma cells were not affected by SWCNTs and the conjugates SC/CNT and DNA/CNT.
The controversy over the use of nanoparticles in everyday products, such as cosmetics, has been going on for a while now. At best, the evidence is inconclusive - it's too early to say whether there is a risk or not. The cosmetics industry of course argues that their nanoparticle-containing products are perfectly safe because no problem has been reported so far. Consumer, health and environmental groups beg to differ and claim that there is a potential risk because we just don't know enough about this issue and that we rather should err on the side of caution. The fact is, as a recent report by the European Commission's Health and Consumer Protectorate states, that at present there is inadequate information on hazard identification, exposure assessment, uptake, the role of physico-chemical parameters of nanoparticles determining absorption and transport across membranes in the gut and lungs, the role of physico-chemical parameters of nanoparticles in systemic circulation determining biokinetics and accumulation in secondary target organs, possible health effects, and translocation of nanoparticles via the placenta to the foetus. The EU report concludes that conventional risk assessment methodologies may be adequate for products that contain soluble and/or biodegradable nanoparticles but not for insoluble and/or biopersistent nanoparticles.
The toxicity issues surrounding carbon nanotubes (CNTs) are highly relevant for two reasons: Firstly, as more and more products containing CNTs come to market, there is a chance that free CNTs get released during their life cycles, most likely during production or disposal, and find their way through the environment into the body. Secondly, and much more pertinent with regard to potential health risks, is the use of CNTs in biological and medical settings. CNTs interesting structural, chemical, electrical, and optical properties are explored by numerous research groups around the world with the goal of drastically improving performance and efficacy of biological detection, imaging, and therapy applications. In many of these envisaged applications, CNTs would be deliberately injected or implanted in the body. For instance, CNT-based intercellular molecular delivery vehicles have been developed for intracellular gene and drug delivery in vitro. What these CNTs do once inside the body and after they discharge their medical payloads is not well understood. Cell culture studies have shown evidence of cytotoxicity and oxidative stress induced by single-walled carbon nanotubes (SWCNTs), depending on whether and to what degree they are functionalized or oxidized. A new study at Stanford University tested non-covalently pegylated SWCNTs as a 'least toxic scenario', and oxidized, covalently functionalized nanotubes as a 'most toxic scenario' in a study on mice. It was found that SWCNTs injected intravenously into nude mice do not appear to have any significant toxicity during an observation period of four months following injection.