Recent Developments in Lyotropic Liquid Crystals as Drug Delivery Vehicles - Self-Assembled Supramolecular Architectures: Lyotropic Liquid Crystals - page 224

critical and optimal chain length of the triglyceride is required to induce the
formation of H II at room temperature. Among the examined TAGs, tricaprylin
(C 8 ) was the most successful, fl exibly accommodating between the tails of the
GMO.
The structural properties of ternary hexagonal mesophases composed of
GMO, tricaprylin, and water were extensively and systematically studied as
was shown in numerous publications (Achrai et al., 2011; Amar-Yuli et al.,
2007a,b, 2008a,b, 2009). Several additives, including dermal penetration
enhancers, were solubilized to control the physical properties of these carriers
(Amar-Yuli et al., 2007b, 2008a,b), such as viscosity and thermal stability. For
instance, the synergistic solubilization of two major hydrophilic (vitamin C,
ascorbic acid, AA) and lipophilic (vitamin E, D- - tocopherol, VE) antioxi-

dants within H II mesophases was reported by Bitan-Cherbakovsky et al. (2009,
2010). This enabled expanding conditions to obtain stable H II mesophases at
room temperature. In addition, it was shown that phosphatidylcholine (PC)
can be embedded into the ternary GMO-TAG-water system (Ben Ishai et al.,
2009; Libster et al., 2007, 2008, 2009a,b). PC was incorporated into the ternary
mesophases because it is known that phospholipid-based structures possess
relatively high thermal stability and enhance transdermal drug permeation
(Kurosaki et al., 1991; Touitou et al., 1994; Spernath and Aserin, 2006) and
transmembrane transport across the digestive tract (Brondsted et al., 1995; Liu
et al., 1999).
Incorporation of PC to the ternary system caused competition for water
binding between the hydroxyl groups of GMO and the phosphate groups of
the PC, leading to dehydration of the GMO hydroxyls in favor of the phos-
pholipid hydration (Libster et al., 2009a). On the macroscopic level, this was
correlated with the improvement of elastic properties and thermal stability of
the H II mesophase (Libster et al., 2007). Structural fl exibility and stability is
essential for a drug delivery system, especially for tuning its physical properties
(such as viscosity) and composition.
Libster et al. (2008) also explored and demonstrated correlations between
the microstructural and mesostructural properties of the reverse hexagonal
LLC, using the environmental scanning electron microscopy (ESEM) tech-
nique. It was shown that the mesoscopic organization of these systems is based
on an alignment of polycrystalline domains. The topography of H II meso-
phases, imaged directly in their hydrated state, as a function of aqueous phase
concentration, was found to possess fractal characteristics, indicating a discon-
tinuous and disordered alignment of the corresponding internal water rods
on the mesoscale. Fractal analysis indicated that the mesoscale topography of
the H II phase was likely to be infl uenced by the microstructural parameters
and the water content of the samples (Libster et al., 2008). Garti and co-
workers also made considerable progress elucidating the solubilization of
therapeutic peptides into the H II mesophase (Cohen-Avrahami et al., 2010;
Libster et al., 2007, 2009a,b; Mishraki et al., 2010a,b).
Lately, for the fi rst time Cohen-Avrahami et al. (2011) used cell-penetrating
peptides (CPPs) as enhancers to overcome the stratum corneum barrier.

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