Nanostructural Features of Lipid Liquid Crystalline Drug Delivery

Systems
Justas Barauskas1,2, Marija Jankunec1, Daiva Taurait1, Laura Adamonyt1,
Markus Johnsson3, Fredrik Tiberg3,4
1

Vilnius University Institute of Biochemistry, Mokslinink 12, LT-08662 Vilnius, Lithuania

Biomedical Science, Faculty of Health and Society, Malm University, SE-20506 Malm,
Sweden
Camurus AB, Slvegatan 41, Ideon Science Park Gamma 1, SE-22370 Lund, Sweden

Physical Chemistry 1, Center for Chemistry and Chemical Engineering, Lund University,
P. O. Box 124, SE-22100 Lund, Sweden

The ability of certain lipids to self-assemble into functional reversed phase nonlamellar liquid crystal (LC) gels in contact with aqueous media, make such systems highly
interesting for use as ambient responsive delivery systems using such functional features as;
bioadhesion, biodegradation, encapsulation and controlled release.1 By exploiting the
liquid-to-LC gel transition triggered on exposure of lipid solutions to aqueous media, it is
possible to combine excellent in vivo encapsulation and extended release properties of some
reversed LC gel phases, with the easy manufacturing and administration properties of
relatively low viscous non-aqueous lipid solutions comprising small amounts of nonaqueous solvent.2
The most frequently used non-lamellar LC forming lipid in drug delivery related
studies has been glycerol monooleate (GMO).34 At physiological conditions in excess
water, GMO forms a bilayer-based bicontinuous cubic phase (V2) with Pn3m space group
representing a three-dimensional network of hydrophilic and hydrophobic domains.
Although a promising candidate for several applications, the one-component GMO system
has limitations with respect to the drug delivery application in the difficulty of
compensating for any phase changes caused by solubilizing drug compounds.5 The use of a
two or multicomponent system typically can alleviate this issue and allows for
compensation of unwanted phase changes by simply adjusting the ratio of the lipid building
blocks.
One example of such a system is the two-component glyceryl monooleyl ether
(GME) and diglycerol monooleate (DGMO) system, where GME has a preference for the
reversed hexagonal LC phase (H2) and DGMO for the planar lamellar LC phase (L).
Between these extremes at full hydration a number of other 3D reversed LC phases were
expected to be formed. In this work full characterization of the phase behavior of ternary
GME/DGME/water system was characterized by small angle X-ray scattering (SAXS). The
xeperiments were performed in both, excess water conditions and at limited hydration.
Temperature stability and phase transformations of most interesting mixtures were also
explored.

The experiments have shown a wide

variety of highly swollen (up to 70 75
wt% or water, with q up to ~0.25 nm-1)
polymorphic LC aggregates formed in this
system depending on composition (Figure
1). Starting from fully hydrated GME and
with increasing DGMO concentration the
following
LC
phase
transformation
sequence is observed: H2 Q230 Q224
Q229 L3 L.
In addition, Figure 2 shows the
temperature behavior of the fully hydrated
GME/DGMO mixtures between weight
ratios of 65/35 and 45/55. As observed,
temperature induced several transformations
of LC phases: Q229 Q224, Q224 H2, L3
Q229 Q224.

Figure 1. SAXS profiles of fully hydrated mixtures

of GME and DGMO.

Figure 2. The temperature behavior of fully hydrated mixtures of GME and DGMO. The
GME/DGMO weight ratios are: 65/35 (a), 55/45 (b), 50/50 (c), and 45/55 (d).

F. Tiberg, M. Johnsson, J. Drug Del. Sci. Techn. 2011, 21, 101.

F. Tiberg, M. Johnsson, C. Nistor, F. Joabsson, in Long-Acting Injections and Implants, CRS, Springer, New York, 2012, p. 315.
3
J. Shah, Y. Sadhale, D. Chilurkuri, Adv. Drug Del. Rev. 2001, 47, 229.
4
C. J. Drummond, C. Fong, Curr. Opin. Colloid Interface Sci. 1999, 4, 449.
5
S. Engstrom, L. Engstrom, Int. J. Pharm. 1992, 79, 113.
2