Physicochemical Stability - Lipid Nanoparticles: Production, Characterization and Stability - page 75

5.2 Stabilization Mechanisms
Stabilisation of the hot emulsion from which nanoparticles form and continued
stabilisation of the nanoparticles once formed are likely to involve quite different
mechanisms. The hot emulsions contains liquid particles which can deform and for
which parameters such as zeta potential are dynamic rather than static, especially
during particle interaction. Stability of the hot emulsion is likely to arise from the
well-known Gibbs-Marangoni effect and is largely driven by the choice of surfactant
(Walstra 1993 ). On cooling, however, the liquid emulsion solidifies to form a disper-
sion, and stability is now likely to relate to the well-known DLVO theory (and recent
variants thereof) (Gambinossi et al. 2014 ; Ohki and Ohshima 1999 ).
The lipid nanoparticles distributed in the dispersion medium are in a constant state
of random “Brownian” motion, and therefore frequently collide. If they “stick” on
collision, then the overall surface area of the system will decrease, a process which
lowers free energy, and consequently the system is thermodynamically unstable.
Only if the particle size is extremely small, as is the case with microemulsions and
micellar solutions, will the entropy caused by the sheer number of particles allow the
system to be thermodynamically stable, Although nanosized particles may reach such
an extreme small size, the particle size usually still remains large enough that the sys-
tem is inherently thermodynamically unstable. The stability of the lipid nanoparticle
dispersions thus depends on ensuring that particles do not “stick” on collision.
The forces that are operative during such collisions include:
• Van der Waals forces
• Electrostatic forces
• Solvation forces
• Electrical double layer compression
• Polymeric inter - particle bridging
A colloidal suspension can be stabilized in both aqueous and non-aqueous media
through two common mechanisms, specifically electrostatic stabilization and
steric stabilization. Electrostatic repulsion can be achieved, for example, by the
addition of ionic stabilizers to the medium; steric stabilization can be accom-
plished, for example, by the addition of (large molecular) non-ionic stabilizers
(Scheler 2012 ).
5.2.1 Electrostatic Stabilization
The electrostatic stabilization of colloidal particles can be explained by the classic
Deraguin Landau Verwey Overbeek (DLVO) theory (Deraguin and Landau 1941 ;
Verwey 1947 ). The DLVO theory assumes that colloidal stability is due to the
additive effect of forces between particles. In particular, DLVO accounts for attrac-
tive van der Waals forces and repulsive electrostatic forces. The van der Waals
forces of attraction between particles arise from electromagnetic attraction. The