Recent Developments in Lyotropic Liquid Crystals as Drug Delivery Vehicles

Recently, self-assembled lyotropic liquid crystals (LLCs) of lipids and water have attracted the attention of both the scientifi c and the applied research communities due to the remarkable structural complexity and practical potential of these nanostructures in diverse applications. The phase behavior of mixtures of glycerol monooleate (monoolein, GMO) was particularly well studied due to the potential utilization of these systems in drug delivery systems, food products, and encapsulation and crystallization of proteins. The present chapter summarizes structural features of LLCs and recent systematic efforts to utilize these for solubilization and the potential release of drugs and biomacromolecules. One of the most interesting applications is the implementation of cell-penetrating peptides in the reversed hexagonal mesophase to enhance the skin-penetrating pattern of a model drug (sodium diclofenac). Liquid crystal vehicles were shown to allow " on demand " targeted release, based on controlling the polymorphism of lyotropic liquid crystalline mesophases. Novel liquid crystalline matrix-gold nanorod hybrid materials were reported to induce light-triggered phase transition of liquid crystalline phases. Hydrophobized gold nanorods (GNRs) have been incorporated within the LLCs, composed of phytantriol and water, to provide remote heating, and trigger the phase transitions on irradiation at close to their resonant wavelength. A new pathway to pH-responsive LLCs, enabling the controlled release of hydrophilic drugs diffusing through the water channels of the mesophases, was also investigated. The system is capable of self-assembling into a reverse bicontinuous cubic phase of Im3m symmetry at pH 7 and transforming into a reverse columnar hexagonal phase at pH 2. Lyotropic liquid crystals were shown to entrap several nucleotides into cubic and lamellar monoolein-based mesophases in order to protect them and enable their release. Deoxyribonucleic acid (DNA) within two types of reverse columnar hexagonal mesophases was studied, one based on pure nonionic lipids and the other decorated by cationic lipids to induce opposite charges at the surfaces of the water channels of the mesophases. This provided new opportunities in the design technologies for DNA transfection and for gene delivery. The main outcomes of the described research demonstrated that control of the physical properties of hexagonal LLC on different length scales is key for rational design of these systems as delivery vehicles for both low-molecular-weight therapeutics and biomacromolecules.