Biopersistence and biodurability have the potential to influence the long-term toxicity and hence pathogenicity of particles that deposit in the body. Therefore, biopersistence and biodurability are ...considered to be important parameters needed for the risk assessment of particles and fibres. Dissolution, as a measure of biodurability, is dependent on the chemical and physical properties (size, surface area, etc.) of particles and fibres and also of the suspension medium including its ionic strength, pH, and temperature. In vitro dissolution tests can provide useful insights as to how particles and fibres may react in biological environments; particles and fibres that release ions at a higher rate when suspended in vitro in a specific simulated biological fluid will be expected to do so when they exist in a similar biological environment in vivo. Dissolution of particles and fibres can follow different reaction kinetics. For example, the majority of micro-sized particles and fibres follow zero-order reaction kinetics. In this case, although it is possible to calculate the half-time of a particle or fibre, such calculation will be dependent on the initial concentration of the investigated particle or fibre. Such dependence was eliminated in the shrinking sphere and fibre models where it was possible to estimate the lifetimes of particles and fibres as a measure of their biodurability. The latter models can be adapted for the dissolution studies of nanomaterials. However, the models may apply only to nanomaterials where their dissolution follows zero-order kinetics. The dissolution of most nanomaterials follows first-order kinetics where dependence on their initial concentration of the investigated nanomaterials is not required and therefore it is possible to estimate their half-times as a measure of their biodurability. In dissolution kinetics for micro-sized and nano-sized particles and fibres, knowledge of dissolution rate constants is necessary to understand biodurability. Unfortunately, many studies on dissolution of nanoparticles and nanofibres do not determine the dissolution rates and dissolution rate constants. The recommendation is that these parameters should be considered as part of the important descriptors of particle and fibre physicochemical properties, which in turn, will enable the determination of their biodurability.
Genetic molecular studies used to understand potential risks of engineered nanomaterials (ENMs) are incomplete. Intracellular residual ENMs present in biological samples may cause assay interference. ...This report applies the high-resolution melt (HRM) feature of RT-qPCR to detect shifts caused by the presence of gold nanoparticles (AuNPs). A universal RNA standard (untreated control) sample was spiked with known amounts of AuNPs and reverse transcribed, where 10 reference genes were amplified. The amplification plots, dissociation assay (melt) profiles, electrophoretic profiles and HRM difference curves were analysed and detected interference caused by AuNPs, which differed according to the amount of AuNP present (i.e. semi-quantitative). Whether or not the assay interference was specific to the reverse transcription or the PCR amplification step was tested. The study was extended to a target gene-of-interest (GOI), Caspase 7. Also, the effect on in vitro cellular samples was assessed (for reference genes and Caspase 7). This method can screen for the presence of AuNPs in RNA samples, which were isolated from biological material in contact with the nanomaterials, i.e., during exposure and risk assessment studies. This is an important quality control procedure to be implemented when quantifying the expression of a GOI from samples that have been in contact with various ENMs. It is recommended to further examine 18S, PPIA and TBP since these were the most reliable for detecting shifts in the difference curves, irrespective of the source of the RNA, or, the point at which the different AuNPs interacted with the assay.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Particles and fibres affect human health as a function of their properties such as chemical composition, size and shape but also depending on complex interactions in an organism that occur at various ...levels between particle uptake and target organ responses. While particulate pollution is one of the leading contributors to the global burden of disease, particles are also increasingly used for medical purposes. Over the past decades we have gained considerable experience in how particle properties and particle-bio interactions are linked to human health. This insight is useful for improved risk management in the case of unwanted health effects but also for developing novel medical therapies. The concepts that help us better understand particles' and fibres' risks include the fate of particles in the body; exposure, dosimetry and dose-metrics and the 5 Bs: bioavailability, biopersistence, bioprocessing, biomodification and bioclearance of (nano)particles. This includes the role of the biomolecule corona, immunity and systemic responses, non-specific effects in the lungs and other body parts, particle effects and the developing body, and the link from the natural environment to human health. The importance of these different concepts for the human health risk depends not only on the properties of the particles and fibres, but is also strongly influenced by production, use and disposal scenarios.
Lessons learned from the past can prove helpful for the future of the field, notably for understanding novel particles and fibres and for defining appropriate risk management and governance approaches.
The commercialisation and everyday use of nanomaterials and nanomaterial-enabled products (NEPs) is rising year-on-year. Responsible development of nanotechnology includes understanding their ...potential implications on health, safety, and the environment (HSE). The health risk assessment of nanomaterials has therefore become one of the major activities of international agencies including the Organisation for Economic Co-operation and Development and the Environmental Protection Agency for protection of human health and the environment. Nationally, with the foresight and the leadership of the Department of Science and Innovation, a HSE programme was initiated to establish the necessary infrastructure to conduct the tests in the hazard identification and exposure assessment that are needed in the risk assessment of nanomaterials synthesised as well as NEPs available in South Africa. Here we present the advances that have been made in elucidating the different facets that are required when undertaking risk assessments of nanomaterials, i.e. physicochemical characterisation, hazard identification, exposure assessment and effects assessment. These facets are increasingly being considered throughout the nanomaterials present in the life cycles of NEPs. South Africa's research contribution to an international understanding of HSE risks of nanomaterials is highlighted and the future direction to generate the necessary information for effective risk communication and management is provided. This will assist in ensuring safer innovation of nanotechnology in South Africa and support the export of locally manufactured nanomaterials as per international requirements.Significance:
Significant contributions of South Africa to the nanomaterial HSE knowledge base are highlighted.
Development of standardised testing methodologies in nanomaterial HSE and protection of human and ecological health through risk assessment of nanomaterials are discussed.
This paper contributes to ensuring safer innovation of nanotechnology in South Africa.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Silver nanoparticles offer a wide range of benefits including their application in several fields such as medical, food, health care, consumer, and industrial purposes. However, unlocking this ...potential requires a responsible and co-ordinated approach to ensure that potential challenges emanating from the use of silver nanoparticles are being addressed. In this study body fluids and environmental media were used to investigate the effects of citrate coated silver nanoparticles (cit-coated AgNPs) to mimic their behaviour in real life situations. Understanding the dissolution kinetics and behaviour of cit-coated AgNPs in simulated biological fluids and synthetic environmental media helps us predict their fate and effects on human health and the environment. The cit-coated AgNPs behaviour significantly varied in acidic and alkaline simulated fluids. Low pH and high ionic strength accelerated the rate and degree of dissolution of AgNPs in simulated fluids. Following exposure to simulated fluids cit-coated AgNPs demonstrated significant changes in agglomeration state and particle reactivity however, the morphology remained unaltered. The slow dissolution rates observed for highly agglomerated cit-coated AgNPs in simulated blood plasma, Gamble’s and intestinal fluids, and freshwater indicate that there is a greater likelihood that the particles will be the cause of the observed adverse effects. In contrast, the fast dissolution rates observed for cit-coated AgNPs in simulated gastric and phagolysosomal fluid and synthetic seawater, the release of the silver ions at a fast rate, will be the cause of their short-term effects.
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•Understanding the dissolution kinetics of AgNPs to predict their effects on human health and the environment.•Low pH and high ionic strength accelerated the rate and degree of dissolution of AgNPs in simulated fluids.•AgNPs demonstrated significant changes in agglomeration state upon exposure to simulated fluids.•Fast dissolution rates observed for AgNPs in simulated acidic fluids & will be the cause of their short-term effects.
It is acknowledged that the physicochemical properties of nanomaterials (NMs) have an impact on their toxicity and, eventually, their pathogenicity. These properties may include the NMs’ surface ...chemical composition, size, shape, surface charge, surface area, and surface coating with ligands (which can carry different functional groups as well as proteins). Nanotopography, defined as the specific surface features at the nanoscopic scale, is not widely acknowledged as an important physicochemical property. It is known that the size and shape of NMs determine their nanotopography which, in turn, determines their surface area and their active sites. Nanotopography may also influence the extent of dissolution of NMs and their ability to adsorb atoms and molecules such as proteins. Consequently, the surface atoms (due to their nanotopography) can influence the orientation of proteins as well as their denaturation. However, although it is of great importance, the role of surface topography (nanotopography) in nanotoxicity is not much considered. Many of the issues that relate to nanotopography have much in common with the fundamental principles underlying classic catalysis. Although these were developed over many decades, there have been recent important and remarkable improvements in the development and study of catalysts. These have been brought about by new techniques that have allowed for study at the nanoscopic scale. Furthermore, the issue of quantum confinement by nanosized particles is now seen as an important issue in studying nanoparticles (NPs). In catalysis, the manipulation of a surface to create active surface sites that enhance interactions with external molecules and atoms has much in common with the interaction of NP surfaces with proteins, viruses, and bacteria with the same active surface sites of NMs. By reviewing the role that surface nanotopography plays in defining many of the NMs’ surface properties, it reveals the need for its consideration as an important physicochemical property in descriptive and predictive toxicology. Through the manipulation of surface topography, and by using principles developed in catalysis, it may also be possible to make safe-by-design NMs with a reduction of the surface properties which contribute to their toxicity.
Abstract This review outlines and compares techniques that are currently available for the sterilization of nanoparticles and addresses the topic of endotoxin contamination. Several techniques are ...available for the removal of microbial contamination from nanoparticles developed for use in nanomedicine applications. These techniques include filtration, autoclaving and irradiation, as well as formaldehyde, ethylene oxide and gas plasma treatments. Of these sterilization methodologies, filtration may potentially remove microbial contamination without altering the physicochemical properties of the carrier nanoparticles, nor affecting their toxicity and functionality. However, no single process may be applied to all nanoparticle preparations and, therefore, it is recommended that each nanoparticle-drug system be validated on a case-by-case basis. From the Clinical Editor This comprehensive review covers the currently available methods for removal of microbial contaminations from nanoparticles for nanomedicine applications. The review highlights the pros and cons of each available method. Authors conclude that there is no single best method and recommend a customized approach for each nanoparticle system.
Exposure to silica and the consequent development of silicosis are well-known health problems in countries with mining and other dust producing industries. Apart from its direct fibrotic effect on ...lung tissue, chronic and immunomodulatory character of silica causes susceptibility to tuberculosis (TB) leading to a significantly higher TB incidence in silica-exposed populations. The presence of silica particles in the lung and silicosis may facilitate initiation of tuberculous infection and progression to active TB, and exacerbate the course and outcome of TB, including prognosis and survival. However, the exact mechanisms of the involvement of silica in the pathological processes during mycobacterial infection are not yet fully understood. In this review, we focus on the host's immunological response to both silica and
, on agents of innate and adaptive immunity, and particularly on silica-induced immunological modifications in co-exposure that influence disease pathogenesis. We review what is known about the impact of silica and
or their co-exposure on the host's immune system, especially an impact that goes beyond an exclusive focus on macrophages as the first line of the defense. In both silicosis and TB, acquired immunity plays a major role in the restriction and/or elimination of pathogenic agents. Further research is needed to determine the effects of silica in adaptive immunity and in the pathogenesis of TB.
The potential for nanoparticles to cause harm to human health and the environment is correlated with their biodurability in the human body and persistence in the environment. Dissolution testing ...serves to predict biodurability and nanoparticle environmental persistence. In this study, dissolution testing using the continuous flow through system was used to investigate the biodurability and persistence of gold nanoparticles (AuNPs), silver nanoparticles (AgNPs) and titanium dioxide nanoparticles (TiO
NPs) in five different simulated biological fluids and two synthetic environmental media to predict their behaviour in real life situations. This study examined the physicochemical properties and agglomeration state of gold, silver and titanium dioxide nanoparticles before and after dissolution tests using three different techniques (UV-vis, XRD and TEM). The UV-vis spectra revealed that all three nanoparticles shifted to higher wavelengths after being exposed to simulated fluids. The titanium powder was found to be mixed with both rutile and anatase, according to XRD examination. The average diameter of gold nanoparticles was 14 nm, silver nanoparticles were 10 nm and titanium dioxide nanoparticles were 25 nm, according to TEM images. The gold and silver nanoparticles were observed to be spherical, but the titanium dioxide nanoparticles were irregular in shape, with some being spherical. The level of dissolved nanoparticles in simulated acidic media was higher in magnitude compared to that dissolved in simulated alkaline media. The results obtained via the continuous flow through dissolution system also displayed very significant dissolution rates. For TiO
NPs the calculated half-times were in the range of 13-14 days, followed by AuNPs ranging between 4-12 days, significantly longer if compared to the half-times of AgNPs ranging between 2-7 days. AuNPs and TiO
NPs were characterized by low dissolution rates therefore are expected to be (bio)durable in physiological surroundings and persistent in the environment thus, they might impose long-term effects on humans and the environment. In contrast, AgNPs have high dissolution rates and not (bio)durable and hence may cause short-term effects. The results suggest a hierarchy of biodurability and persistence of TiO
NPs > AuNPs > AgNPs. It is recommended that nanoparticle product developers should follow the test guidelines stipulated by the OECD to ensure product safety for use before it is taken to the market.
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