Formation Of Lyotropic Liquid Crystalline Phases Research Articles

Limitation and potential of lignin-assisted stabilisation of oriented liquid crystalline cellulosic mesophase

This study aimed at progressing in the fundamental understanding of the lignin-assisted microstructural stabilisation observed in solution-processed materials based on the polymer blend of hydroxypropyl cellulose and hardwood organosolv lignin. Mechanical analysis, polarised infrared spectroscopy and wide-angle X-ray scattering of shear cast blend films revealed that the effect of lignin on the flow-oriented cellulosic mesophase is also valid for blends composed of ethyl cellulose as liquid crystalline matrix polymer and lignin derived oligomers from base-catalysed depolymerisation as dispersed “microstructural cementing agent”. The results underline the significant role of the solvent diffusion between the continuous cellulosic and the dispersed lignin phase, which is ascribed to polymer-/oligomer-solvent interactions. An abundance of the solvent within the lignin phase caused the disruption of the microstructural stabilisation effect. The concept of a balanced proton-donor activity was introduced linking the solvent diffusion with the lyotropic liquid crystalline phase formation, the macro- and microstructural blend morphology and aspects regarding the solution processing.

The search for new amphiphiles: synthesis of a modular, high-throughput library.

Amphiphilic compounds are used in a variety of applications due to their lyotropic liquid-crystalline phase formation, however only a limited number of compounds, in a potentially limitless field, are currently in use. A library of organic amphiphilic compounds was synthesised consisting of glucose, galactose, lactose, xylose and mannose head groups and double and triple-chain hydrophobic tails. A modular, high-throughput approach was developed, whereby head and tail components were conjugated using the copper-catalysed azide–alkyne cycloaddition (CuAAC) reaction. The tails were synthesised from two core alkyne-tethered intermediates, which were subsequently functionalised with hydrocarbon chains varying in length and degree of unsaturation and branching, while the five sugar head groups were selected with ranging substitution patterns and anomeric linkages. A library of 80 amphiphiles was subsequently produced, using a 24-vial array, with the majority formed in very good to excellent yields. A preliminary assessment of the liquid-crystalline phase behaviour is also presented.

Formation of Inverse Topology Lyotropic Phases in Dioleoylphosphatidylcholine/Oleic Acid and Dioleoylphosphatidylethanolamine/Oleic Acid Binary Mixtures

The addition of saturated fatty acids (FA) to phosphatidylcholine lipids (PC) that have saturated acyl chains has been shown to promote the formation of lyotropic liquid-crystalline phases with negative mean curvature. PC/FA mixtures may exhibit inverse bicontinuous cubic phases (Im3m, Pn3m) or inverse topology hexagonal phases (HII), depending on the length of the acyl chains/fatty acid. Here we report a detailed study of the phase behavior of binary mixtures of dioleoylphosphatidylcholine (DOPC)/oleic acid (OA) and dioleoylphosphatidylethanolamine (DOPE)/oleic acid at limiting hydration, constructed using small-angle X-ray diffraction (SAXD) data. The phase diagrams of both systems show a succession of phases with increasing negative mean curvature with increasing OA content. At high OA concentrations, we have observed the occurrence of an inverse micellar Fd3m phase in both systems. Hitherto, this phase had not been reported for phosphatidylethanolamine/fatty acid mixtures, and as such it highlights an additional route through which fatty acids may increase the propensity of bilayer lipid membranes to curve. We also propose a method that uses the temperature dependence of the lattice parameters of the HII phases to estimate the spontaneous radii of curvature (R0) of the binary mixtures and of the component lipids. Using this method, we calculated the R0 values of the complexes comprising one phospholipid molecule and two fatty acid molecules, which have been postulated to drive the formation of inverse phases in PL/FA mixtures. These are -1.8 nm (±0.4 nm) for DOPC(OA)2 and -1.1 nm (±0.1 nm) for DOPE(OA)2. R0 values estimated in this way allow the quantification of the contribution that different lipid species make to membrane curvature elastic properties and hence of their effect on the function of membrane-bound proteins.

Lyotropic Liquid Crystals Formed from ACHC-Rich β-Peptides

We have examined the effect of β-peptide modifications on the propensity of these helical molecules to form lyotropic liquid crystalline (LC) phases in water. All of the β-peptides we have examined contain 10 residues. In each case, at least three residues are derived from trans-2-aminocyclohexanecarboxylic acid (ACHC), which strongly promotes folding to a 14-helical conformation. The structural features varied include the number of ACHC residues, the nature and spatial arrangement of charged side chains (cationic vs anionic), and the identity of groups at the β-peptide termini. We found that relatively small changes (e.g., swapping the positions of a cationic and an anionic side chain) could have large effects, such as abrogation of LC phase formation. The trends revealed by sequence-property studies led to the design of LC-forming β-peptides that bear biomolecular recognition groups (biotin or the tripeptide Arg-Gly-Asp). Structural analysis via circular dichroism and cryo-transmission electron microscopy revealed the existence of two different types of self-associated species, globular aggregates and nanofibers. Nanofibers are the predominant assembly formed at concentrations that lead to LC phase formation, and we conclude that these nanofibers are the functional mesogens. Overall, these studies show how the modularity of β-peptide oligomers enables elucidation of the relationship between molecular structure and large-scale self-assembly behavior.

Lamellar crystalline self-assembly behaviour and solid lipid nanoparticles of a palmityl prodrug analogue of Capecitabine—A chemotherapy agent

An amphiphile prodrug, 5'-deoxy-5-fluoro-N(4)-(palmityloxycarbonyl) cytidine or 5'-deoxy-5-fluoro-N(4)-(hexadecanaloxycarbonyl) cytidine (5-FCPal), consisting of the same head group as the commercially available chemotherapeutic agent Capecitabine, linked to a palmityl hydrocarbon chain via a carbamate bond is reported. Thermal analysis of this prodrug indicates that it melts at ∼115 °C followed quickly by degradation beginning at ∼120 °C. The neat solid 5-FCPal amphiphile acquires a lamellar crystalline arrangement with a d-spacing of 28.6±0.3 Å, indicating interdigitation of the hydrocarbon chains. Under aqueous conditions, solid 5-FCPal is non-swelling and no lyotropic liquid crystalline phase formation is observed. In order to assess the in vitro toxicity and in vivo efficacy in colloidal form, solid lipid nanoparticles (SLNs) with an average size of ∼700 nm were produced via high pressure homogenization. The in vitro toxicity of the 5-FCPal SLNs against several different cancer and normal cell types was assessed over a 48 h period, and IC(50) values were comparable to those observed for Capecitabine. The in vivo efficacy of the 5-FCPal SLNs was then assessed against the highly aggressive mouse 4T1 breast cancer model. To do so, the prodrug SLNs were administered orally at 3 different dosages (0.1, 0.25, 0.5 mmol/mouse/day) and compared to Capecitabine delivered at the same dosages. After 21 days of receiving the treatments, the 0.5 mmol dose of 5-FCPal exhibited the smallest average tumour volume. Since 5-FCPal is activated in a similar manner to Capecitabine via a 3 step enzymatic pathway with the final step occurring preferentially at the tumour site, formulation of the prodrug into SLNs combines the advantage of selective, localized activation with the sustained release properties of nanostructured amphiphile self-assembly and multiple payload materials thereby potentially creating a more effective anticancer agent.

Nanostructured self-assembly materials from neat and aqueous solutions of C18 lipid pro-drug analogues of Capecitabine—a chemotherapy agent. Focus on nanoparticulate cubosomes™ of the oleyl analogue

A series of prodrug analogues based on the established chemotherapy agent, 5-fluorouracil, have been prepared and characterized. C18 alkyl and alkenyl chains with increasing degree of unsaturation were attached to the N4 position of the 5-fluorocytosine (5-FC) base via a carbamate bond. Physicochemical characterization of the prodrug analogues was carried out using a combination of differential scanning calorimetry, cross-polarized optical microscopy, X-ray diffraction and small-angle X-ray scattering. The presence of a monounsaturated oleyl chain was found to promote lyotropic liquid crystalline phase formation in excess water with a fluid lamellar phase observed at room temperature and one or more bicontinuous cubic phases at 37 °C. The bulk phase was successfully dispersed into liposomes or cubosomes at room and physiological temperature respectively. In vitro toxicity of the nanoparticulate 5-FCOle dispersions was evaluated against several normal and cancer cell types over a 48 h period and exhibited an IC50 of ∼100 μM against all cell types. The in vivo efficacy of 5-FCOle cubosomes was assessed against the highly aggressive mouse 4T1 breast cancer model and compared to Capecitabine (a water-soluble commercially available 5-FU prodrug) delivered at the same dosages. After 21 days of treatment, the 0.5 mmol 5-FCOle treatment group exhibited a significantly smaller average tumour volume than all other treatment groups including Capecitabine at similar dosage. These results exemplify the potential of self-assembled amphiphile prodrugs for delivery of bioactives in vivo.

Lyotropic Liquid Crystalline Self-Assembly in Dispersions of Silver Nanowires and Nanoparticles

We report demixed nematic lyotropic liquid crystalline phase formation in dispersions of silver nanowires and spherical nanoparticle aggregates in ethylene glycol and water. This phase is observed in samples in spite of the high density, large aspect ratio, and long relaxation times of the nanowires which have an average length of 6.8 microm. Remarkably, in the biphasic region, the nanowire-rich liquid crystalline phase exhibits a strandlike morphology which has only previously been reported for single-walled carbon nanotube liquid crystals. Shearing predominantly liquid crystalline dispersions results in both significant nanowire alignment and nanowire-aggregate demixing. The results of this research suggest that the nanoparticle contaminants common to many synthesis schemes facilitate liquid crystalline phase formation and that these dispersions can be processed into aligned coatings.

Lyotropic Liquid Crystals from Designed Helical β-Peptides

We demonstrate that 14-helical beta-peptides can self-assemble to form lyotropic liquid crystalline (LC) phases in water. beta-Peptides 1-4 were designed to form globally amphiphilic 14-helices of increasing length. Optical microscopy showed that several of these beta-peptides formed LC phases in aqueous solutions at concentrations as low as 2.5 wt % (15 mM). Liquid crystallinity appears to require the adoption of a globally amphiphilic conformation because a scrambled sequence, 5, does not display LC behavior. Thermal stability and reversibility of LC phase formation were assessed by variable temperature 2H NMR spectroscopy and optical microscopy. The LC phase formed by beta-peptide 3 at 10 wt % is disrupted above 40 degrees C in D2O and re-forms within minutes upon cooling. LC phase behavior for solutions of 3 is influenced by concentration and net charge. These studies demonstrate that highly folded 14-helical beta-peptides can produce LC phases at shorter lengths than do alpha-helical alpha-peptide mesogens and can provide a basis for tailoring properties of LC phases for future applications.