Biomedical Engineering Reference
In-Depth Information
concentration of nanoparticles in blood depends on the route of administration, it can contribute to
potential nanotoxicity as it determines the access of these nanoparticles to different cells and organs
of the body. For example, polymeric and lipid nanoparticles with a size range above 100 nm can
be nontoxic if applied dermally compared with the administration in an invasive way like intrave-
nously as injection. In the latter case, they could potentially irritate the immune system after uptake
by macrophages. Nanotoxicity should be assessed if there is an increased risk due to a special route
of pharmaceutical administration [37].
7.3.2.8 Biocompatibility of Polymeric/Lipid Nanoparticles
Biocompatibility of polymers and lipid excipients is another essential parameter to be taken into
account while assessing PN and SLN toxicity for drug delivery systems in various applications.
Usually, polymers and lipids utilized in PNs and SLNs are inert and do not generate any undesired
response from the body.
7.3.2.9 Excipients/Residual Solvents Used during the Preparation of Polymeric/Lipid
Nanoparticles
Organic solvents are commonly used in the preparation of PNs and can add to the toxicity of the
formulation. Care should be taken to remove all the residual organic solvent as they have a strong
potential of toxicity. Residual solvents are not a toxicity concern for SLN but high concentrations of
surfactants/emulsifiers/preservatives present in SLNs can cause nanotoxicity. Studies on SLN con-
taining sterylamine and different triglycerides suggested that the toxicity of the SLN is dependent
on the composition and method of purification used. In the study, dialysis was found to be the most
efficient method to remove excess surfactant thus reducing the toxicity [91]. The positively charged
surfactant used in the preparation of SLNs can interact with the negatively charged cellular mem-
brane resulting in possible toxicity.
7.4 METHODS FOR NANOTOXICITY ASSESSMENT
Although there is no standard protocol for nanotoxicity testing currently, it will suffice to mention
that the key elements of a toxicity screening strategy should include physicochemical characteriza-
tion of nanoparticles and various
in vitro
assays to establish the nanotoxicity of nanoparticles.
7.4.1 p
hysIcocheMIcal
c
haracterIzatIoN
The adequate physicochemical characterization of nanomaterials prior to undertaking experiments
for
in vitro
toxicity assessments is extremely important. The major physicochemical characteriza-
tion includes (1) size, including surface area, size distribution, chemical composition (purity crystal-
linity, electronic properties, etc.); (2) solubility; (3) shape and aggregation; and (4) surface structure
including surface reactivity and particle reactivity in solution [85,92].
7.4.2
I
n
V
Itro
c
ell
c
ulture
t
echNIques
In vitro
cell culture techniques could be used for the characterization of nanoparticle uptake and
localization, biodistribution and qualitative analysis of nanotoxicity. Further, various cell culture
assays for cytotoxicity (altered metabolism, decreased growth, lytic or apoptotic cell death), pro-
liferation, genotoxicity, and altered gene expression can provide important assessment about the
nanotoxicity [93].
7.4.2.1 Cell Viability Assay
Nanocarriers can be evaluated in terms of their potential toxicity to the cells by the use of various
cell viability assays. These assays are basically indicators of cellular damage. Several standard
