Chemistry Reference
In-Depth Information
of peptides and proteins in medicine is hampered by their minimal permeabil-
ity and passage through biological barriers, short half-life in the systemic cir-
culation, and low bioavailability resulting from degradation due to either
proteolysis or hydrolysis. With sterically stabilized lipid nanovector systems,
the challenges for protein delivery, imposed by enzymatic degradation, early
elimination from the circulation, capturing by the reticuloendothelial system,
accumulation at nontargeted organs or tissues, and risk of immune response
could be progressively surmounted.
Lipid nanoparticulate carrier systems of therapeutic biomolecules can
provide a reservoir for peptides with a high degree of protection against enzy-
matic degradation and other destructive factors. The supramolecular architec-
ture of the lipid carriers constraints the direct contact of the peptide molecules
with the circulation medium and can be designed and built up so as to with-
stand the destabilizing infl uence of the biological environment. Self-assembly
offers additional advantages through the association of several kinds of active
and matrix components in one liquid crystalline nanocarrier object. The release
properties and the biocompatibility of the self-assembled lipid nanocarriers
with cells and tissues can be specifi cally optimized. All these advantages make
the self-assembled nanodispersed lipid systems very interesting vectors for the
administration of peptide and protein molecules.
Lipids of various types have been studied for the vectorization of peptides
with different routes of administration (Angelova, 2005a,b, 2008; Jorgensen
et al., 2006; Nylander et al., 1996; Rizwan et al., 2009; Shah et al., 2001). In the
presence of an aqueous medium, amphiphilic lipids self-organize so as to
minimize the exposure of their nonpolar chains to the surrounding water
phase, whereas their polar head groups remain in contact with the solution
(Drummond and Fong, 1999). Hydrated lipids may adopt different structural
organizations, for instance, lamellar, inverted cubic, inverted hexagonal, and
sponge phases (Fig. 11.2 ).
The arrangement of amphiphilic lipids in aggregates is governed by inter-
molecular hydrophobic and electrostatic interactions, temperature, degree of
hydration, and the geometry of the molecules. The supramolecular packing is
determined through the balance between the attractive interactions of the
hydrophobic residues, on one hand, and the repulsive interactions between the
polar head groups, on the other hand. The “critical packing parameter” is
defi ned as
p
v/al
, where
v
and
l
is the volume and length of the apolar part
of the amphiphile, respectively, and
a
corresponds to the area occupied by the
lipid molecule at the hydrophobic-hydrophilic interface (Israelachvili et al.,
1976). The steric packing constrains give indications for predicting the aggre-
gation state of the lipids in aqueous medium. Depending on the critical packing
parameter, one may distinguish globular micelles (
=
3
), cylindrical geome-
tries such as elongated micelles or worms in a hexagonal phase (
3
p
<
1
<<
p
1
2
),
quasi-plane bilayers in vesicles or multilamellar phases (
p
∼
1), inverted hex-
agonal (
p
>
1) and bicontinuous cubic membranes (
p
>
1), or sponge phase
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