Dissolution and biodurability: Important parameters needed for risk assessment of nanomaterials

Abstract

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.

Comparative toxicity and biodistribution assessments in rats following subchronic oral exposure to copper nanoparticles and microparticles

“…The release of toxic ions has the potential to influence the toxicity of NPs [34–36]. Most NPs are rarely soluble at normal physiological conditions; however, their dissolution can be accelerated in acidic conditions [37, 38].…”

“…Thus, the differences in dissolution play a crucial role in the gap of toxicological responses between Cu NPs and Cu MPs. In addition, the biopersistence of NPs influences long-term toxicity and is considered to be an important parameter needed for the risk assessment of NPs [36]. Therefore, further studies will be necessary to investigate whether the toxic responses of Cu NPs observed in this study are transient or persistent responses.…”

Disposition of intravenously or orally administered silver nanoparticles in pregnant rats and the effect on the biochemical profile in urine

“…Distribution, disposition, and elimination also reveal if a ENMs are persistent. Persistence (biodurability) of ENMs in biological systems is considered one of the main contributors to particle and fiber toxicity (Utembe, et al 2015), since the longer the ENM persists, the higher the risk there is for an adverse outcome. The most classic example of the serious consequences of persistence in toxicology might be asbestos, which is not metabolized and has an estimated clearance half-time measured in years to decades (Churg and Wright 1994).…”

Developments in Pressurized Gyration for the Mass Production of Polymeric Fibers

“…As the hydrophilic polymer dissolves, drug molecules are released as fine colloidal particles . The high surface area to volume ratio of these fibers further enhances drug dissolution due to the increased contact area to the dissolution media . PG overcomes a significant limitation in the large‐scale manufacture of micro‐ and nanofibrous drug systems, allowing for production rates in excess of kilograms per hour …”