Environmental Engineering Reference
In-Depth Information
composed with different material and surface chemical can be correlated to the
physical factors like material composition, physical size/surface area, shape, and
surface chemical property [
8
].
6.3.3 Excipient Selection
It has been shown that genotoxity and oxidative stress of quantum dots made up of
core/shell CdSe/ZnS can be attenuated by PEG encapsulation when studied by
neutral comet assay and H2AX foci formation [
9
]. Diagnotic iron oxide
nanoparticles proved its effectiveness to determine mechanistic interactions at the
nanobiointerface with cells of the immune, neuroglial and neurovascular units
in vivo [
10
]. Selection of surfactant, surfactant concentration, chemical nature of
polymer, % polymer used, solvent used in nanoparticle manufacturing process are
very important. Some surfactant has inherited toxicity profile. In case of lipid
nanoparticles, nature of lipid, lipid concentration, and type of technique,
e.g. solvent evaporation are key parameters. Excipient compatibility, excipient
stability after nanonization, and freeze drying are other areas to take into consid-
eration. Purity of excipient and nanoparticle is equally important
in toxicity
determination.
The outer structure of nanoparticles determines the protein adsorption patterns
in vivo which ultimately determine the fate of nanoparticle [
11
]. Excipient choice
determines the protein adsorption on nanoparticle and its ultimate fate,
e.g. polysorbate 80 is known to induce adsorption of ApoE on the surface of
nanoparticle which led to brain targeting. Similarly, nanoparticles surface modified
with disaccharide could led to macrophage targeting and ultimately to spleen
[
12
]. This kind of excipient directed, drug delivery systems can be used for
organ-specific targeting for various diseases, e.g. splenic targeting for HIV, diag-
nostic or imaging for polysorbate 80 decorate nanoparticles. Readers are advised to
refer a chapter on application of multidimensional gel electrophoresis in this topic
to know the basics of in vitro protein characterization.
6.3.4 Selection of Cell Lines
In vitro assays are simple, faster, and more cost-efficient to that of animal studies.
Assessment of toxicity endpoints beforehand, complexity of animal model, and
metabolic activity are determining factors in obtaining in vivo biodistribution and
are mostly neglected. Cytotoxicty reactions involve effects on cell signaling,
membrane perturbations, influence on the cellular electron transfer cascades, pro-
duction of cytokines, chemokines and ROS, transcytosis and intercellular transport,
gene regulation, overt toxic reactivity, no observable toxicity, and cell necrosis or
apoptosis. A major challenge with in vitro assay is determination of correct and
