Chemistry Reference
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structures (
p
1). The hydrated lipids display structural properties that are
intermediate between those of disordered liquid states and well-ordered crys-
talline solid states. They are referred to as liquid crystalline phases or meso-
phases (Fig. 11.2). By their particular architecture and capacity of incorporating
guest substances, liquid crystalline phases of lipids represent a source of nano-
structures for vectorization of peptides and proteins.
>
11.2.2.1 Vesicles and Liposomes
Among the known lipid carriers, ves-
icles and liposomes are the most widely employed in drug delivery (Gabizon
et al., 1994; Kawasaki et al., 2002; Klibanov et al., 1990; Martina et al., 2008)
and have characteristics suitable for peptide and protein encapsulation. Such
nanoparticles can be obtained from hydrated phospholipids or lipid mixtures
forming lamellar phases (Fig. 11.2b). They are biocompatible, biologically
inert, and display little toxicity and antigenic reactions. Liposomes are closed
bilayer structures, composed of one or more phospholipid membranes, enclos-
ing an aqueous volume (Fig. 11.2a). Lipophilic substances can be incorporated
into the lipid bilayer, whereas hydrophilic compounds can be entrapped in the
aqueous core. The aqueous compartments are used for the encapsulation and
protection of soluble peptides or proteins (Walde and Ichikawa, 2001). There
are numerous techniques for vesicle and liposome preparation, but some of
them are well-suited for manipulations compatible with the maintaining of the
integrity of the protein or peptide molecules (Table 11.2). A major obstacle
for the development of liposomal formulations has been imposed by aggrega-
tion phenomena and a risk of degradation during storage due to physicochemi-
cal instability (Torchilin, 2005 ).
Several studies have been conducted on encapsulation of peptides or pro-
teins in liposomes (Gregoriadis et al., 1999; Martins et al., 2007). Liposomes
are often produced by hydration of a lipid fi lm followed by energy input, for
instance, sonication. Upon mechanical agitation, the hydrated lipid sheets
disconnect and self-assemble to form vesicles. The bilayer structure is main-
tained by the hydrophobic effect that inhibits the interaction between the lipid
hydrocarbon chains and water. The morphology of the vesicles is infl uenced
by the chemical composition and the charge of the lipids, which in some cases
can be controlled by pH (Kawasaki et al., 2002; Oberdisse et al., 1996). The
diameter of a lipid vesicle can vary from 20 nm to several hundred microm-
eters (Walde and Ichikawa, 2001). The release of active biomolecules, nanopar-
ticle (NP) stability, and the in vivo biodistribution are determined by the
vesicles surface charge, stealth properties, size, and membrane fl uidity (Tor-
chilin, 2005). The membrane permeability can be modulated by variations
in the lipid bilayer composition, phospholipids nature, inclusion of additives
such as cholesterol or dioleoylphosphatidylethanolamine, DOPE, as examples
(Gregoriadis et al., 1999). PEGylated derivatives can be incorporated in
the lipid bilayer in order to avoid a premature capture of the liposomes by
the reticuloendothelial system (Gabizon et al., 1994; Klibanov et al., 1990). The
development of sterically stabilized NPs (stealth liposomes) can be further
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