Interactions of biomacromolecules with reverse hexagonal liquid crystals: Drug delivery and crystallization applications

Recently, self-assembled lyotropic liquid crystals (LLCs) of lipids and water have attracted the attention of both scientific and applied research communities, due to their remarkable structural complexity and practical potential 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. Among the studied lyotropic mesophases, reverse hexagonal LLC (HII) of monoolein/water were not widely subjected to practical applications since these were stable only at elevated temperatures. Lately, we obtained stable HII mesophases at room temperature by incorporating triacylglycerol (TAG) molecules into the GMO/water mixtures and explored the physical properties of these structures.The present feature article summarizes recent systematic efforts in our laboratory to utilize the HII mesophases for solubilization, and potential release and crystallization of biomacromolecules. Such a concept was demonstrated in the case of two therapeutic peptides—cyclosporin A (CSA) and desmopressin, as well as RALA peptide, which is a model skin penetration enhancer, and eventually a larger macromolecule—lysozyme (LSZ). In the course of the study we tried to elucidate relationships between the different levels of organization of LLCs (from the microstructural level, through mesoscale, to macroscopic level) and find feasible correlations between them. Since the structural properties of the mesophase systems are a key factor in drug release applications, we investigated the effects of these guest molecules on their conformations and the way these molecules partition within the domains of the mesophases. The examined HII mesophases exhibited great potential as transdermal delivery vehicles for bioactive peptides, enabling tuning the release properties according to their chemical composition and physical properties. Furthermore, we showed a promising opportunity for crystallization of CSA and LSZ in single crystal form as model biomacromolecules for crystallographic structure determination.The main outcomes of our 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 and crystallization medium for biomacromolecules.

Schematic presentation of HII mesophase, showing the packing of water-filled rods, surrounded by lipid layers.Figure optionsDownload high-quality image (100 K)Download as PowerPoint slideResearch highlights
► Monoolein-based HII mesophases, which are stable at room temperature.
► Structural characterization of the HII mesophases.
► Incorporation of peptides and proteins into reverse hexagonal mesophases.
► Sustained delivery of biomacromolecules via HII mesophases.
► Crystallization of biomacromolecules within HII mesophases.