Recent Developments in Lyotropic Liquid Crystals as Drug Delivery Vehicles - Self-Assembled Supramolecular Architectures: Lyotropic Liquid Crystals - page 232

pharmaceuticals. Such vehicles can provide enhanced drug solubility, relative
protection of the solubilized drugs, and controlled release of drugs, while
avoiding substantial side effects (Ericsson et al., 1991; Fong et al., 2009; Shah
et al., 2001). The effi ciency of the LLC delivery system can be further enhanced
in transdermal delivery, where peptide degradation and low absorption rates
are much less relevant.
Signifi cant progress has been made during the last decade in the character-
ization of the interactions of peptides and proteins with LLCs, mainly for
crystallographic and drug delivery purposes. LLCs have been shown to provide
sustained release of drug molecules with a range of physicochemical proper-
ties (Drummond and Fong, 2000; Shah and Paradkar, 2005; Shah et al., 2001).
The cubic phase was shown to host a range of water-soluble biomacromole-
cules for use in controlled-release applications. Clogston and Caffrey (2005)
systematically examined biomacromolecules ranging from a single amino acid
(tryptophan) to complex proteins and nuclear deoxyribonucleic acid (DNA).
These investigators found that for a given cubic phase, the rate of diffusion
depends on the molecular size of the specifi c diffusing molecule. Shah and
Paradkar (2005) prepared in situ a cubic phase system of GMO. This system
provided protection to the metalloenzyme seratiopeptidase (STP) in the
gastric environment and gave delayed and controlled release with no initial
burst after oral administration.
Although the cubic phase has been proposed and studied as a drug deliv-
ery vehicle, there is relatively little information about the interactions of
peptides and proteins with the H II mesophases and the therapeutic potential
of these structures. Libster and co-workers explored and controlled the physi-
cal properties of H II mesophases to use these systems as drug delivery vehi-
cles for biologically active peptides and proteins. The results of this structural
research enabled signifi cant expansion of the application spectrum of hexago-
nal LLCs, utilizing them for the solubilization of peptides and proteins
(Libster et al., 2007, 2009a,b, 2011), into this mesophase and its utilization as
sustained drug delivery vehicle. Two model cyclic peptides, cyclosporin A (11
amino acids) and desmopressin (9 amino acids), of similar molecular weight
but with very different hydrophilic and lipophilic properties, were chosen to
demonstrate the feasibility of using the H II mesophase (Libster et al., 2011).
In addition, a larger peptide, RALA (Cohen-Avrahami et al., 2010) (16 amino
acids), was solubilized into the H II structures as a model skin penetration
enhancer. Finally, a larger macromolecule, LSZ protein (129 amino acids),
was directly incorporated into a GMO-based H II mesophase (Mishraki et al.,
2010a,b ).
With the aim of designing a biologically inspired carrier in which the
encapsulation and the delivery of DNA can be effi ciently controlled, Amar-
Yuli et al. (2011a) have designed two lipid-based columnar hexagonal LLCs,
which can accomplish two opposite roles while maintaining the same liquid
crystalline symmetry. The fi rst system was based on a nonionic lipid, such as
monoolein, while the second system was modifi ed by a low additional amount