Biomedical Engineering Reference
In-Depth Information
not interfere with the NMs and does not induce any toxicity of its own. For example, some studies
found that phosphate-buffered saline, commonly used as a vehicle for dose delivery, is a poor dis-
persion agent (Sager et al. 2007, Sayes et al. 2007). Once delivered into the body, NMs may interact
with other components of the biological system, such as proteins, different salt concentrations, and
variable pH values, to form unstable suspensions, thereby negatively affecting their biodistribution
and activity (Buford et al. 2007). Hence, the results thus obtained may be conflicting.
1.7.4 c oNsIderatIoNs for p reveNtINg N aNotoxIcIty
As it has been highlighted, the importance of the tight control over NM parameters is crucial for the
prevention and control of nanotoxicity. One of the most prominent factors that increases the vari-
ability of the properties and activity of NMs is agglomeration. The phenomenon of agglomeration
involves the adhesion of particles to each other, mainly because of van der Waal's forces, which
dominate at the nanoscale level due to the increased surface area to volume ratio (Powers et  al.
2007). NMs agglomerate after their synthesis in both the dry and suspension forms. The challenge
for synthetic chemists is to prevent agglomeration, as it can lead to changes in physical and chemi-
cal properties. The major properties affected are size, size distribution, surface-to-volume ratio and,
hence, surface reactivity. Since these parameters play a major role in the toxicity of NPs and are
altered due to agglomeration, it is prudent to account for these changes in the study design (Borm
et al. 2006, Teeguarden et al. 2007).
Agglomeration is influenced by several intrinsic and extrinsic factors, such as the composition
of NMs and their concentration, size, surface coating, zeta potential, and temperature, among
others (Teeguarden et al. 2007). It is well known that NPs can pass through biological barriers
due to their small size. Agglomeration can alter their biological responses due to a decrease in
the total available surface area, leading to an underestimation of toxic potential, especially in the
case of drug delivery and safety and toxicity assessments (Sager et al. 2007). There are differ-
ent methods available to deagglomerate NMs. Sonication is the most preferable and widely used
method because it disperses NPs in a liquid by cavitation and does not have much of an effect
on the properties of the particles. However, the attained deagglomeration is incomplete, as the
particles do not reach their primary size and display the tendency to reagglomerate over time
(Murdock et al. 2008). Another important method for preventing the agglomeration of NMs is
surface modification. The particles can be coated with polymers or dispersed in ionic or nonionic
surfactants (Farah et  al. 2008, Sager et  al. 2007, Skebo et  al. 2007, Wick et  al. 2007). While
surface modification allows the particles to be stabilized and avoids agglomeration, it also raises
concerns that they may shield or influence the effects of NMs on biological systems (Warheit
2008, Derfus et  al. 2004, Warheit et  al. 2005). The stability of such surface coatings inside a
biological environment is another critical issue.
At the initial synthesis stage, the scientist may need to consider specific, physical parameters.
However, in order to control the risk of NMs at all lifecycle points, interdisciplinary collabora-
tions may be required. Additionally, owing to the increase in the production of NMs, the chances
of their release into the environment and their subsequent effects on ecosystems are becoming
important issues that need to be addressed. To do that, it is first necessary to assess the fate and
behavior of NMs in the environment. It is still unclear how, at what concentrations, and in what
forms, the NMs will be released into the environment. The answers to these questions will guide
the formulation of regulatory guidelines that will protect the ecosystem and will also permit the
full industrialization of the benefits that nanotechnology offers. It is important to focus current
research efforts on the release, behavior (reaction to changes in environments), and fate (aggrega-
tion, adsorption, etc.) of NMs. A lifecycle assessment of the release of NMs into the environment
is, therefore, imperative as the implementation of effective and protective regulatory policies
(Navarro et al. 2008).
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