Multicompartment Lipid Nanocarriers for Targeting of Cells Expressing Brain Receptors - Self-Assembled Supramolecular Architectures: Lyotropic Liquid Crystals - page 324

can be fragmented, with the help of dispersing agents under agitation, to form
nanosized colloidal-type amphiphilic aggregates. The internal structures of the
obtained lipid nanoparticles may adopt various kinds of supramolecular orga-
nizations (Larsson, 2000; Larsson and Tieberg, 2005; Seddon and Templer,
1995), which can accommodate peptides either in the aqueous channel com-
partments, in the lipid bilayers, or at the lipid-water interfaces. In cubic phases
(Fig. 11.2c), the created three-dimensional lipid membrane surface area essen-
tially exceeds that of a liposome interface. Hence, the capacity for incorpora-
tion of guest molecules in nonlamellar, multicompartment-type lipid carriers
is considerably enhanced (Angelova et al., 2003; Barauskas et al., 2005; Caboi
et al., 2001; Shah et al., 2001).
In the majority of studies on nonlamellar liquid crystalline nanoparticle
preparation, monoolein (MO) has been used as a biodegradable, biocompat-
ible, and nontoxic lipid, which is listed in the Food and Drug Administration
(FDA) regulation as an inactive component. MO has a low solubility in water,
but it easily swells in contact with an aqueous phase and, therefore, exhibits a
lyotropic behavior (Hyde et al., 1984; Larsson, 1989; Luzzati, 1997). Its phase
diagram is well characterized (Qiu and Caffrey, 2000). The long-chain unsatu-
rated monoglyceride forms liquid crystalline phases upon hydration, in par-
ticular inverse bicontinuous cubic phases of the Ia3d (Q 230 ) and Pn3m (Q 224 )
types (Angelov et al., 2006, 2007, 2009; Mariani et al., 1988; Qiu and Caffrey,
2000). In mixed systems with soluble polymeric surfactant, another cubic liquid
crystalline phase of the Im3m (Q 229 ) symmetry has been described (Gustafsson
et al., 1997; Larsson, 2000; Nakano et al., 2001).
Cubosomes Cubosomes are multicompartment lipid particles with the inter-
nal structure of an inverted bicontinuous cubic liquid crystalline type (Angelov
et al., 2006; Gustafsson et al., 1996; Nakano et al., 2001; Siekmann et al., 2002;
Spicer and Hayden, 2001). The cubic lipid membrane is periodically organized
and divides intertwined networks of aqueous channels (Fig. 11.3). The struc-
tural properties of the cubosomes characterize them as multicompartment
vehicles for the delivery of peptides, proteins, and other molecules (Angelova
et al., 2003, 2005a,b, 2008, 2011a; Caboi et al., 2001; Nylander et al., 1996,
Rizwan et al., 2009). The cubosome structure offers the possibility to entrap
hydrophilic substances in the water channels and to control the biomolecular
release by a slow diffusion process (Anderson and Wennerström, 1990; Boyd,
2003; Fong et al., 2009). Modifi cation of the charges in the liquid crystalline
phase can infl uence the kinetics of release (Lynch et al., 2003). Toward paren-
teral administration, the colloidal dispersions of cubosome particles can be
stabilized by the inclusion of amphiphilic polymers (Gustafsson et al., 1997;
Murgia et al., 2010; Nakano et al., 2001; Spicer and Hayden, 2001). Investiga-
tions with rats on the interaction of plasma components with cubosomes,
composed of monoolein and Pluronic F-127, have shown a prolonged circula-
tion (Leesajakul et al., 2004 ).