204
Abstract Drug delivery nanocarriers (DDNCs) are very suitable systems in drug
transport to site-specific targets. The physicochemical characteristics that make
DDNCs promising systems for disease therapy can be also correlated with potential
adverse effects. In the development of functional DDNCs, both efficacy and safety
assessment are crucial. Until now, there is no established testing strategy to perform
nanomaterial toxicological evaluation. Several in vitro cell culture models and testing protocols are commonly applied for the safety profile assessment of a nanocarrier; however, a large amount of disperse and conflicting data are generally provided
in scientific literature. Thus, systematic research on the toxicological effects of
nano-based systems is crucial due to their increasing development, production, and
usage. This chapter highlights the critical aspects regarding nanotoxicity assessment, addressing the most important analytical strategies/techniques and endpoints,
from the physicochemical properties’ characterization of DDNCs to their biological
influence and behavior in cells and organisms.
Keywords Nanotoxicity · Nanocarriers · In vitro assays · Nanocarrier
characterization · Analytical methods
8.1 Introduction
Nanotechnology deals with the manipulation of matter, in atomic and molecular
levels, at nanoscale leading to alterations in its properties (Zarbin 2014). During the
last decades, the achieved breakthroughs in nanotechnology have also been translated in new materials, developing more effective tools for therapy and diagnostics
with applications in the biomedical field (Cole and Holland 2015). Nanotechnology
medical applications, also referred as nanomedicine, intends to address the diagnostic, treatment and prevention of acute and chronic diseases, leading to the development of drug delivery nanocarriers (DDNCs). DDNCs engineering and development
main goals consist of (i) solubility and bioavailability improvement of hydrophobic
drugs; (ii) drugs circulatory time increase, avoiding metabolic processes before
reaching therapeutic site; (iii) diminishing side effects with the decrement of administered doses; (iv) drug-targeting to specific tissues and cells or individual pathogens and biomolecules; and (v) controlled drug release (Moghimi et al. 2005). To
date, there are already several established and commercially available
nanotechnology- based products ad formulations. Biodegradable “soft” platforms,
such as liposomes, micelles, emulsions, and/or other polymeric and protein nanostructures, are preferred for therapeutic delivery applications. Examples of FDAapproved are Abraxane
®
, Doxil
®
, DaunoXome
®
, and Copaxone
®
(Dong et al. 2016).
The growing development, production, and use of engineered nanomaterials
(NMs) is inevitably leading to direct and indirect effects in humans, as well as emissions into the environment. Therefore, the assessment and evaluation of the potential risks for human health and environment as a result of exposure to NMs is also a
matter of concern. The term nanotoxicology was coined for the first time in 2004 by
M. C. Teixeira et al.
Abstract Drug delivery nanocarriers (DDNCs) are very suitable systems in drug
transport to site-specific targets. The physicochemical characteristics that make
DDNCs promising systems for disease therapy can be also correlated with potential
adverse effects. In the development of functional DDNCs, both efficacy and safety
assessment are crucial. Until now, there is no established testing strategy to perform
nanomaterial toxicological evaluation. Several in vitro cell culture models and testing protocols are commonly applied for the safety profile assessment of a nanocarrier; however, a large amount of disperse and conflicting data are generally provided
in scientific literature. Thus, systematic research on the toxicological effects of
nano-based systems is crucial due to their increasing development, production, and
usage. This chapter highlights the critical aspects regarding nanotoxicity assessment, addressing the most important analytical strategies/techniques and endpoints,
from the physicochemical properties’ characterization of DDNCs to their biological
influence and behavior in cells and organisms.
Keywords Nanotoxicity · Nanocarriers · In vitro assays · Nanocarrier
characterization · Analytical methods
8.1 Introduction
Nanotechnology deals with the manipulation of matter, in atomic and molecular
levels, at nanoscale leading to alterations in its properties (Zarbin 2014). During the
last decades, the achieved breakthroughs in nanotechnology have also been translated in new materials, developing more effective tools for therapy and diagnostics
with applications in the biomedical field (Cole and Holland 2015). Nanotechnology
medical applications, also referred as nanomedicine, intends to address the diagnostic, treatment and prevention of acute and chronic diseases, leading to the development of drug delivery nanocarriers (DDNCs). DDNCs engineering and development
main goals consist of (i) solubility and bioavailability improvement of hydrophobic
drugs; (ii) drugs circulatory time increase, avoiding metabolic processes before
reaching therapeutic site; (iii) diminishing side effects with the decrement of administered doses; (iv) drug-targeting to specific tissues and cells or individual pathogens and biomolecules; and (v) controlled drug release (Moghimi et al. 2005). To
date, there are already several established and commercially available
nanotechnology- based products ad formulations. Biodegradable “soft” platforms,
such as liposomes, micelles, emulsions, and/or other polymeric and protein nanostructures, are preferred for therapeutic delivery applications. Examples of FDAapproved are Abraxane
®
, Doxil
®
, DaunoXome
®
, and Copaxone
®
(Dong et al. 2016).
The growing development, production, and use of engineered nanomaterials
(NMs) is inevitably leading to direct and indirect effects in humans, as well as emissions into the environment. Therefore, the assessment and evaluation of the potential risks for human health and environment as a result of exposure to NMs is also a
matter of concern. The term nanotoxicology was coined for the first time in 2004 by
M. C. Teixeira et al.