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with liquid crystalline organizations, suitable for encapsulation of neuropro-
tective peptides. The fragmentation and dispersion of the bicontinuous cubic
phase of MO to form nanometer-sized objects was realized using the PEGylated
amphiphile DOPE-PEG
2000
. The latter can self-associate in surfactant micelles
at concentrations above its critical micellar concentration (cmc
1 0
− 5
M ) .
The molar fraction of DOPE-PEG
2000
in the lipid mixtures was set at 2 mol %
with respect to monoolein. A higher PEGylation percentage could essentially
infl uence the mean packing parameter of the lipid assembly and may favor
the formation of small vesicles rather than particles from a dispersed cubic
phase. Electrostatic stabilization of the multicompartment NPs was achieved
by varying the molar fractions of the charged lipid molecules. It was taken into
account that the fatty acids, OA and EPA, are negatively charged at pH 7.4.
Such co-lipids are anticipated to contribute to the formation of cubosomes
(Nakano et al., 2001).
∼
2
×
11.4.1.1 Characterization of Nanoparticulate Systems with Increasing
Molar Fractions of the Charged Co-Lipid Oleic Acid (OA) in the Mixtures
MO/DOPE-PEG
2000
/OA
Nanoparticulate MO/DOPE - PEG
2000
/OA samples
with increasing molar fractions of oleic acid (0, 5, 10, 15, 20, and 30 mol %
OA) were studied by QELS (at dilution 150-
l sample/1-ml buffer) as a func-
tion of the time elapsed after preparation. The results for the particles size
distribution in freshly prepared samples (J0) as well as after 2 days (J2) of
particle storage at room temperature showed a coexistence of two major
populations of nanoobjects (Fig. 11.4). The corresponding mean NP diameters
were about 40 and 100 nm at low molar OA molar fractions and can be
ascribed to the presence of vesicle and multicompartment NPs in the aqueous
dispersions. The NP dispersions showed an overall stability with the time
elapsed after preparation. However, a tendency to form larger aggregates
(most probably cubosomes) can be observed as a function of the co-lipid molar
fraction (Fig. 11.4 ).
Other cryo-TEM (transmission electron microscopy) studies (Ferreira
et al., 2006; Spicer and Hayden, 2001) have demonstrated that cubosome par-
ticles, with internal structure refl ecting the organization of the original cubic
phase of monoolein, can coexist with smaller (vesicle or transient) particles
even in the presence of 30 mol % OA (see Fig. 11.3). Formation of coexisting
vesicles and dispersed particles from the monoolein cubic phase has been
induced also by the co-surfactant poloxamer 407 (Gustafsson et al., 1997;
Spicer and Hayden, 2001).
μ
11.4.1.2 Stability of Dispersed NP Systems upon Dilution
The stabil-
ity of the MO/DOPE-PEG
2000
(98/2 mol/mol) NP sample was studied by
QELS, on the seventh day after their preparation, upon dilutions of 1/10 and
1/1000 in buffer medium (Fig. 11.5). The volume distribution profi le of the NPs
was kept almost unchanged upon dilution. The obtained data confi rmed that
the lipid organization in this sample is not a micellar one. In fact, the sample
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