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assembly of porous nanodroplets (“nanocubosomes”) with diameters between
30 and 60 nm. Large protein molecules have been suggested to be confi ned at
the interfaces between the nanocubosomes inside the multicompartment pro-
teocubosome particles.
Hexosomes
Depending on temperature and water composition, monoglyc-
eride lipids and phytantriol, in mixtures with coamphiphiles, can form also an
inverted hexagonal phase (Angelov et al., 2011b; Dong et al., 2006; Fong et al.,
2009; Qiu and Caffrey, 2000; Rizwan et al., 2009). By adding surfactants and
supplying mechanical energy, this liquid crystalline phase can be dispersed in
excess aqueous medium to form hexosomes. Nanostructures, obtained from
an inverted hexagonal phase (Fig. 11.2d), have been reported as vehicles for
the delivery of proteins and peptides. In particular, the encapsulation of lyso-
zyme has received attention as a model protein (Mishraki et al., 2010; Zabara
et al., 2011). The preparation of aqueous colloidal dispersions from a reverse
hexagonal phase has been evidenced by electron microscopy (Ferreira et al.,
2006; Gustafsson et al., 1997). The hexosome nanoparticles, formed by self-
assembly of monoolein and oleic acid (Ferreira et al., 2006), have found appli-
cation as nanodispersions for local delivery of the peptide cyclosporine A
(Lopes et al., 2006).
Sponge Phase and Spongosomes
The sponge (L
3
) phase has been regarded
as a bicontinuous bilayer phase (Fig. 11.2e) that is a disordered version of
bicontinuous cubic lipid phases (Bender et al., 2008; Merclin et al., 2004;
Wadsten et al., 2006). Landh and Larsson (1993) have patented the use of
colloidal L
3
-phase particles with stabilized interfaces. Sponge phases have
been widely investigated for their swelling properties and drug encapsulation
(Alfons and Engstrom, 1998; Angelov et al., 2009, 2011b; Merclin et al., 2004).
To our knowledge, no study has described yet the peptide or protein release
from colloidal L
3
-phase nanoparticles (spongosomes). Such particles could
coexist with cubosomes, exemplifying the possibility of developing self-
assembled colloidal systems with multiphase release characteristics (Baraus-
kas et al., 2006). The manufacturing of thermodynamically stable vesicles from
a sponge phase also presents interest for future pharmaceutical applications
(Imura et al., 2005 ).
11.2.2.3 Other Lipid Systems for Peptide and Protein Vectoriza-
tion
Solid lipid nanoparticles (Almeida and Sauto, 2007; Martins et al., 2007;
Mehner and Mäder, 2001) have been studied as carriers for proteins and pep-
tides such as insulin or somatostatin. Nanoemulsions, microemulsions, and
emulsions have been used as vehicles for ovokinine, which is a vasodilator
peptide (Fujita et al., 1995; Jorgensen et al., 2006; Martins et al., 2007). Other
vectors, called “layersomes,” which are vesicles surface coated by polymer
multilayers (Ciobanu et al., 2007), as well as solid triglyceride nanoparticles,
have served for the encapsulation of calcitonin (Garcia-Fuentes et al., 2005).
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