Lessons Learned from Pharmaceutical Nanomaterials - Safety of Nanomaterials along Their Lifecycle - page 116

and polydisperse samples. In order to validate a DLS size measurement, it is essen-
tial to use other size measurement methods such as Nanoparticle Tracking Analysis
(NTA). NTA is based on visual detection of single nanoparticles via analyzing
their size by Brownian motion related to temperature and viscosity of a suspen-
sion (Carr and Malloy 2006). NTA compared to DLS enables indirect nanoparticle
visualization and detects various nanoparticle populations. In DLS measurements,
small amounts of larger particles have a strong influence and shift the mean size to
a higher size distribution (Filipe, Hawe, and Jiskoot 2010; James and Driskell 2013).
For this reason, NTA is an important technique to complement DLS measurements.
Furthermore, it is possible to choose from various other sizing techniques like size
exclusion chromatography, analytical ultracentrifugation, or magnetic sedimen-
tation. From the microscopic techniques, electron microscopies such as scanning
electron microscopy (SEM) and transmission electron microscopy (TEM) provide
additional information on size, mono-, and polydispersity by simultaneously visual-
izing the particulate morphology. In addition, atomic force microscopy (AFM) can
be used (Grobelny et al. 2009).
6.3.1.2 Shape and Structure
Nanoparticles shape and their surface functionalization charge have influence, for
example, on translocation into biological barriers and cell membranes. Thus, shape
and charge are responsible for increasing or decreasing nanoparticle uptake (Nangia
and Sureshkumar 2012). Dependent on nanoparticle composition, there are dif-
ferent microscopic techniques such as SEM, TEM, or AFM to clarify their three-
dimensional structure. For example, a coated nanoparticle with a dense core and a
polymeric shell can easily be enlightened by means of TEM, but for nanoparticle
compositions of several similar raw materials, it is difficult to exhibit their structure.
For this issue we need some appropriate methods for evaluating nanoparticle com-
position and structure.
6.3.1.3 Charge
In most cases it is important to examine the “charge” of nanoparticles. Laser doppler
microelectrophoresis is a possible method to determine the electrophoretic motilities
of particles in suspensions. With this analyzing method we are capable of measuring
the zeta potential also named as charge of nanoparticles (Cooper 2004). Formulating
new nanopharmaceuticals by using the right starting material can approximately
predestinate the charge and therefore also the application. Different applications
expect specific zeta potentials; for example, formation of nanoplexes by using posi-
tively charged nanoparticles combined with negatively charged nucleic acids (Nafee
et al. 2012).
6.3.1.4 Chemical Identity
In comparison to clarifying the structure of nanoparticles there are more accurate
techniques to determine their chemical identity. By quantifying the different spectro-
scopic analysis techniques such as Fourier transform infrared spectroscopy, Raman
spectroscopy (Shao et al. 2007), nuclear magnetic resonance spectroscopy (Wawer
and Diehl 2011), or X-ray powder diffraction (Brittain 2001), it is possible to obtain