Search

Ordered amphiphile self-assembly materials with a tunable three-dimensional (3D) nanostructure are of fundamental interest, and crucial for progressing several biological and biomedical applications, including in meso membrane protein crystallization, as drug and medical contrast agent delivery vehicles, and as biosensors and biofuel cells. In binary systems consisting of an amphiphile and a solvent, the ability to tune the 3D cubic phase nanostructure, lipid bilayer properties and the lipid mesophase is limited. A move beyond the binary compositional space is therefore required for efficient engineering of the required material properties. In this critical review, the phase transitions upon encapsulation of more than 130 amphiphilic and soluble additives into the bicontinuous lipidic cubic phase under excess hydration are summarized. The data are interpreted using geometric considerations, interfacial curvature, electrostatic interactions, partition coefficients and miscibility of the alkyl chains. The obtained lyotropic liquid crystal engineering design rules can be used to enhance the formulation of self-assembly materials and provides a large library of these materials for use in biomedical applications (242 references). [ABSTRACT FROM AUTHOR]

Amphiphile self-assembly materials, which contain both a hydrophilic and a hydrophobic domain, have great potential in high-throughput and combinatorial approaches to discovery and development. However, the materials chemistry community has not embraced these ideas to anywhere near the extent that the medicinal chemistry community has. While this situation is beginning to change, extracting the full potential of high-throughput approaches in the development of self-assembling materials will require further development in the synthesis, characterization, formulation, and application domains. [ABSTRACT FROM AUTHOR]

The effect of chain branching on glycolipid thermotropic and lyotropic phases was investigated for a series of synthetic β-D-glucosides derived from Guerbet alcohols, whose total hydrocarbon chain length ranged from C8 to C24. The compounds, which can be viewed as isosteric mimics for glycoglycerolipids, were synthesised in high purity and their liquid crystalline phases were studied using optical polarising microscopy (OPM), and small-angle X-ray diffraction. When dry, the shortest compound (total C8) exhibits a monotropic Lα phase while longer ones (C16 and C20) adopt inverse hexagonal HII phases. The C24 compound forms an ordered lamellar phase at room temperature, but exhibits a metastable HII phase upon cooling. Curiously the intermediate chain length homologue (C12) adopts an isotropic inverse micellar (L2) phase in the dry state over the range of temperatures studied. Upon hydration, the C8 compound dissolves, and the C12 compound forms a fluid lamellar Lα phase. The C16 Guerbet glucoside (i.e. β-Glc-C10C6) exhibits an inverse bicontinuous cubic phase of space group Ia3d in excess water, never previously observed in branched-chain lipids, and very seldom observed in excess water. The C20 compound remains in the HII phase upon hydrating, with the lattice parameter swelling substantially. [ABSTRACT FROM AUTHOR]

The lyotropic phase behaviour of a library of sugar-based amphiphiles was investigated using high-throughput small-angle X-ray scattering (SAXS). Double unsaturated-chain monosaccharide amphiphiles formed inverse hexagonal and cubic micellar (Fd3m) lyotropic phases under excess water conditions. A galactose-oleyl amphiphile from the library was subsequently formulated into hexosome nanoparticles, which have potential uses as drug delivery vehicles. The nanoparticles were shown to be stable at elevated temperatures and non-cytotoxic up to at least 200 μg mL −1 . [ABSTRACT FROM AUTHOR]

Abstract: An amphiphile prodrug, 5′-deoxy-5-fluoro-N4-(palmityloxycarbonyl) cytidine or 5′-deoxy-5-fluoro-N4-(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±0.3Å, 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 ∼700nm 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 48h period, and IC50 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, 0.5mmol/mouse/day) and compared to Capecitabine delivered at the same dosages. After 21days of receiving the treatments, the 0.5mmol 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. [Copyright &y& Elsevier]