209
All the advantages aforementioned and related to DDNCs as therapeutic agents
can provide an outstanding solution for drug efficacy and safety improvement, as
well as a great technological advance in the biomedical field (Demetzos and
Pippa 2014).
8.3 Nanomaterials Physicochemical Parameters Evaluation
Toxicological research and assessment for engineered DDNCs must consider the
highly dynamic physicochemical properties of NMs. NMs synthesis is a process
that results in several chemical and physical transformations and/or modifications,
which will also influence the interaction mechanisms with biological systems and
their resulting toxicity. Nowadays, new NMs are being developed with large chemical and structural diversity, which leads to highly variable interactions with living
systems and, subsequently, to difficulties in the establishment of toxicity evaluation
standard protocols (Hassan and Singh 2014). However, there is a commonly agreed
minimum set of NMs physicochemical properties and their characterization studies
for nanotoxicity assessment. These properties include chemical composition, size,
shape, surface characterization, crystallinity, and agglomeration/aggregation state
(Kim et al. 2014).
The first critical physicochemical property that influences NMs toxicity is their
chemical composition, once single elements chemical reactivity and toxicity in biological media differ when they are arranged in a nanosystem. Common analytical
technologies that are suitable for NMs chemical composition include spectroscopy
analysis (e.g., X-ray photoelectron spectroscopy (XPS), Raman spectroscopy,
energy dispersive X-ray analysis (EDX), inductively coupled plasma (ICP), or
Fourier transform infrared spectroscopy (FTIR)) and nuclear magnetic resonance
(NMR) (Kim et al. 2014).
The size of the nanostructured carriers is one of the features, which differentiates
them completely from a range of conventional drug carriers. The compounds considered at a nanoscale are featured in the colloidal size range, between 0.1 nm and
500 nm/1 μm (Souto et al. 2007, 2020a; Mahant et al. 2020); however, for systemic
administration in therapeutics, nanoparticle size that is considered suitable ranges
between 2 and 200 nm (Jo et al. 2015). Size and shape are crucial factors that define
both preferential internalization mechanisms and uptake efficiency, conditioning
thus the toxicological behavior of NMs in biological environments. Thus, the size
determination is an essential measurement after production of nanocarriers, and a
variety of appropriate analytical techniques includes microscopy techniques (transmission electron microscopy (TEM), scanning electron microscopy (SEM), atomic
force microscopy (AFM)) and X-ray diffraction (XRD) (Kim et al. 2014, 2015).
However, the most commonly used technique is dynamic light scattering (DLS),
which allows the detection of the particle size (Z-Ave) and the polydispersity index
(PDI), at the same time. These parameters are essential during the optimization
8 In Vitro Methodologies for Toxicological Assessment of Drug Delivery Nanocarriers
All the advantages aforementioned and related to DDNCs as therapeutic agents
can provide an outstanding solution for drug efficacy and safety improvement, as
well as a great technological advance in the biomedical field (Demetzos and
Pippa 2014).
8.3 Nanomaterials Physicochemical Parameters Evaluation
Toxicological research and assessment for engineered DDNCs must consider the
highly dynamic physicochemical properties of NMs. NMs synthesis is a process
that results in several chemical and physical transformations and/or modifications,
which will also influence the interaction mechanisms with biological systems and
their resulting toxicity. Nowadays, new NMs are being developed with large chemical and structural diversity, which leads to highly variable interactions with living
systems and, subsequently, to difficulties in the establishment of toxicity evaluation
standard protocols (Hassan and Singh 2014). However, there is a commonly agreed
minimum set of NMs physicochemical properties and their characterization studies
for nanotoxicity assessment. These properties include chemical composition, size,
shape, surface characterization, crystallinity, and agglomeration/aggregation state
(Kim et al. 2014).
The first critical physicochemical property that influences NMs toxicity is their
chemical composition, once single elements chemical reactivity and toxicity in biological media differ when they are arranged in a nanosystem. Common analytical
technologies that are suitable for NMs chemical composition include spectroscopy
analysis (e.g., X-ray photoelectron spectroscopy (XPS), Raman spectroscopy,
energy dispersive X-ray analysis (EDX), inductively coupled plasma (ICP), or
Fourier transform infrared spectroscopy (FTIR)) and nuclear magnetic resonance
(NMR) (Kim et al. 2014).
The size of the nanostructured carriers is one of the features, which differentiates
them completely from a range of conventional drug carriers. The compounds considered at a nanoscale are featured in the colloidal size range, between 0.1 nm and
500 nm/1 μm (Souto et al. 2007, 2020a; Mahant et al. 2020); however, for systemic
administration in therapeutics, nanoparticle size that is considered suitable ranges
between 2 and 200 nm (Jo et al. 2015). Size and shape are crucial factors that define
both preferential internalization mechanisms and uptake efficiency, conditioning
thus the toxicological behavior of NMs in biological environments. Thus, the size
determination is an essential measurement after production of nanocarriers, and a
variety of appropriate analytical techniques includes microscopy techniques (transmission electron microscopy (TEM), scanning electron microscopy (SEM), atomic
force microscopy (AFM)) and X-ray diffraction (XRD) (Kim et al. 2014, 2015).
However, the most commonly used technique is dynamic light scattering (DLS),
which allows the detection of the particle size (Z-Ave) and the polydispersity index
(PDI), at the same time. These parameters are essential during the optimization
8 In Vitro Methodologies for Toxicological Assessment of Drug Delivery Nanocarriers