Lipid nanoparticles with solid particle matrix are derived
from o/w emulsions by simply replacing the liquid lipid (oil) by
a solid lipid, i.e. being solid at body temperature. The first
generation of solid lipid nanoparticles (SLN) was developed at
the beginning of the nineties [1]. They were produced from a
solid lipid only. In the second generation technology of the
nanostructured lipid carriers (NLC), the particles are produced
by using a blend of a solid lipid with a liquid lipid, this blend
also being solid at body temperature [2].
The production process is identical for both particles SLN
and NLC. The solid lipid or lipid blend is melted, the
pharmaceutical or cosmetic active dissolved in the melted
lipid phase which is subsequently dispersed by high speed
stirring in a hot aqueous surfactant/stabilizer solution of
equivalent temperature. The obtained pre-emulsion is homogenized
in a high pressure homogenizer yielding a hot o/
w nanoemulsion. After cooling the emulsion droplets crystallize
forming lipid nanoparticles with solid particle matrix, depending
on the starting material either SLN or NLC.
The advantage of the second generation technology is the
increased loading with actives compared to SLN and firmer
inclusion of the active inside the particle matrix during the shelf
life. By preparing the particles from a solid lipid, especially
highly purified solid lipids, the particle matrix tends to form a
relatively perfect crystal lattice leaving limited space to
accommodate the active (Fig. 1, left). This limits the loading
capacity and can lead to expulsion of active from the lipid
matrix during storage [3]. In contrast, the use of a lipid mixture
with very differently structured (sized) molecules distorts the
formation of a perfect crystal. The particle matrix contains many
imperfections providing space to accommodate the active in
molecular form or as amorphous clusters (Fig. 1, right). One
could state that “the perfectness” of the NLC system is its
“imperfectness” in its crystalline structure.
In the second half of the nineties there was an increasing interest
in investigating the SLN for dermal application, especially for
cosmetic use. Interesting cosmetic molecules were incorporated
such as e.g. retinol and retinylpalmitate [5], vitamin E and vitamin
E acetate [6] and coenzyme Q 10 [7]. An example for pharmaceutical
actives is the incorporation of corticoids, such as
prednicarbate [8]. At the turn of the millennium the NLC were
developed [9] which – based on the controlled nanostructuring of
the particle matrix – provide advantages with regard to loading
capacity and long-termstability (firm inclusion of actives, physical
stability of suspension). For cosmetic applications requiring a high