Chemistry Reference
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the lipid membrane and the aqueous buffer, leading to a certain destabilization
of lipid NPs with regard to steric shielding. The diluted lipid objects show a
preference of merging into multicompartment particles with larger sizes and
forming a more stable (bulk) phase, which for the monoglyceride lipid MO is
the bicontinuous cubic phase.
Figure 11.6a shows that the proportion of the small NPs (vesicles or cubo-
somal intermediates) with respect to the large particles (multicompartment
cubosomes or spongosomes) changes with the dilution, but the two types of
NP populations are maintained, upon dilution, through the electrostatic stabi-
lization provided by the charged lipid OA. This conclusion is confi rmed by the
analysis of the OD curves determined at different concentrations (Fig. 11.6b).
The scattering of light by lipid objects can be considered, in a fi rst approxima-
tion, as proportional to the factor
V
2
/
4
, where
V
is the volume of the particles
λ
and
is the optical wavelength. The changes in the OD, normalized by the
total lipid concentration, showed very similar profi les as a function of the dilu-
tion (Fig. 11.6b). This confi rms the overall conservation of the lipid particle
organizations despite the dilution. A closer examination of the curves in Figure
11.6b reveals an increase in the {OD/[total lipid]} factor when the sample
concentration diminishes, which indicates a slight tendency of the lipid NP
systems to reorganize into populations with a larger average particle size upon
dilution. A fusion of small (vesicle) particles into larger multicompartment
particles (cubosomes) may explain the observed aggregation upon dilution.
This hypothesis is consistent with the cryo-TEM observations reported in the
literature (Ferreira et al., 2006).
λ
11.4.1.3 Incorporation of a Bioactive Co-Lipid (EPA) in the PEGylated
Liquid Crystalline Nanosystems
The charged component (oleic acid) in
the self - assembled NPs of MO/DOPE - PEG
2000
/OA was progressively substi-
tuted by the bioactive, polyunsaturated fatty acid, EPA. This omega-3 fatty
acid (20 : 5) appears to exhibit a high degree of conformational fl exibility, which
can affect the organization and curvature of the mixed lipid membranes. The
total molar fraction of the charged lipids (i.e., the sum of OA and EPA) was
fi xed at 15 mol % with respect to the MO in the mixtures. It was found that
this molar fraction results in mean NP sizes, which are optimal (
120 nm) for
passage through membranes. Keeping constant the molar fraction (15 mol %)
of the charged molecules in the lipid carriers, the NP size distribution was
investigated as a function of the EPA content in the MO/DOPE-PEG
2000
/OA/
EPA systems. Figure 11.7 summarizes the QELS results about the time stabil-
ity of the NP size distributions in MO/DOPE-PEG
2000
/OA/EPA mixtures con-
taining increasing amounts of a polyunsaturated fatty acid (EPA). The lipid
nanodispersions prepared with higher molar fractions of EPA, with respect to
OA, showed a more narrow size distribution after 4 days of storage (Fig. 11.7).
Correspondingly, the NP system MO/DOPE-PEG
2000
/EPA (83/2/15 mol %)
showed a higher stability over time as compared to the system containing
15 mol % of OA only.
∼
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