Lessons Learned from Pharmaceutical Nanomaterials - Safety of Nanomaterials along Their Lifecycle - page 115

Currently, we are missing a concrete and obligatory determination if nanopar-
ticles should be regulated separately in addition to their bulk counterpart or not.
Due to the size of nanoparticles the question is arising: Are nanoparticles different
from conventional drug products and do they need special testing? In spite of that,
many investigate obvious characteristics of nanopharmaceuticals, such as physical/
chemical parameters and their toxicological effects. Some institutions started to struc-
ture standard protocols for nanoparticle design and investigation. One pioneer, the
Nanotechnology Characterization Laboratory (NCL), is trying to establish standard
protocols for nanoparticles in cancer research. The NCL aims to speed up translation
of nanotechnology in the field of cancer therapy. They provide the service of test-
ing selected, promising nanopharmaceuticals in their facilities as preclinical study.
Moreover, they defined an assay cascade starting with the physicochemical charac-
terization followed by in vitro and in vivo characterization, by collection, creation,
and providing standard protocols for nanoparticle characterization. In the progress of
investigation, there are already some very well-defined assays and protocols for physi-
cochemical and in vitro characterization. Nevertheless, there are several established
assays missing in the in vivo area such as nanoparticle immunotoxicity, genotoxicity,
and mutagenicity. Guidance documents to standardize methods and protocols (as far
as the diverse nature of nanopharmaceuticals and the status of quality assurance of
the assays allow this already) will simplify the development process and the com-
parability between formulations. The following short overview of techniques makes
no claim to be complete. The aim is rather to highlight characterization possibilities,
nanoscientists need to choose the best suited technique(s) from.
6.3.1 C urrent s tatus of n anoPartiCle C haraCterization
At the nanoscale, it is not possible to directly look at and evaluate objects. To qual-
ify prepared nanoparticles, different methods are used, and the complementary use
of them describes their physical and chemical parameters. Ideally, the nanopar-
ticle characterization consists of size, charge, shape, and chemical identity. While
the following part is common for all types of nanoparticles, nanopharmaceuticals
have an important additional level. The drug content, drug structure (crystal or
amorphous), and localization within the carrier (surface adsorption vs. encapsula-
tion) are important for good prediction of the drug effect. The ADME effects of the
carrier have impact on the pharmacokinetic profile of the active ingredient (Zolnik
and Sadrieh 2009)
6.3.1.1 Size
One of the main properties is of course the nanoparticle size. For medical/pharma-
ceutical applications the nanoparticle size is defined as a size range between 1 nm
and 1000 nm (Wagner et al. 2008). To characterize size properties, there are dif-
ferent methods, which should be used complementarily. Photon correlation spec-
troscopy (PCS) also known as dynamic light scattering (DLS) uses scattered light
of particles to determine their size distribution profile in suspensions (Berne and
Pecora 1976). DLS is a method for high statistical representative size measurement.
Nevertheless, it has its weaknesses in relation to size distribution of monodisperse