Characterization - Lipid Nanoparticles: Production, Characterization and Stability - page 48

software imaging devices can help overcome these issues. Single particle counting
techniques, such as electron microscopy, also generally make it difficult to observe
any aggregation in particles such that only an intrinsic size is obtained and not an
effective size.
4.2 Particle Morphology and Ultrastructure
Along with particle size, dispersity and composition, the morphology and ultra-
structure are important properties of nanoparticles and their formulations which
can control properties such as encapsulation efficiency. Morphology generally
relates to the exterior of the particle and may be characterized by shape and sur-
face structure whilst ultrastructure generally relates to the interior of the particle
and can relate to internal partitioning through, for example, a core-shell structure.
Ultrastructure can also relate to the formulation itself, indicating the presence and
orientation of the various components of the formulation. These must include the
nanoparticle itself, but can also include structures such as micelles which may be
simultaneously present.
Spherical particles have the smallest possible specific surface area for any
given shape of particle and hence, are stabilized with the smallest amount of sur-
factant. Furthermore, because spherical particles have the longest diffusion path-
ways, they offer the potential for controlled (i.e. slow) release of incorporated
drugs. A spherical shape also provides minimum contact with the surrounding
aqueous medium, thus, providing protection to the incorporated drugs. On the
other hand, anisometric particles require a greater amount of surfactant for stabi-
lization. This is desirable when the drug is to be incorporated into the surfactant
layer or adsorbed onto the particle surface. Particle shape, thus, may influence
the loading capacity and release properties of the drugs from the lipid nanopar-
ticles. The results obtained from PCS and LD can also be influenced by the ani-
sometric shape of the particles. Particle size results from PCS and LD should
therefore be corroborated with electron microscopic techniques to characterize
the shape of the lipid nanoparticles.
Different components within the lipid nanoparticle dispersions may organise
themselves into a number of different structures, both within and without the nan-
oparticle itself. The ultrastructure of systems should be given due consideration
in predicting the organization of encapsulated drug components within the disper-
sions. For example, surfactants that stabilize the lipid nanoparticles within the dis-
persion may self-assemble to form additional colloidal structures such as micelles.
Such structures have a lipophilic domain which may pocket some of the drug mol-
ecules. The presence of these additional colloidal structures may influence drug
incorporation and release. All these factors point out that the performance of lipid
nanoparticles—drug incorporation, release and stability are influenced by particle
size, shape and structure. It is, thus, necessary to investigate the morphology of
lipid nanoparticles.