Reversed hexagonal lyotropic liquid-crystal and open-shell glycodendrimers as potential vehicles for sustained release of sodium diclofenac.

The effect of second, third, and fifth generations of poly(propylene imine) glycodendrimers-open maltose shell (PPI-Mal) on reverse hexagonal (HII) mesophase and on the release of sodium diclofenac (Na-DFC) drug was investigated. The HII mesophase comprised glycerol monooleate (GMO)/tricaprylin (TAG) in a weight ratio of 90/10 and 20 wt % water (+0.5 wt % PPI-Mal of each generation) without or with 0.

Lipid polymorphism in lyotropic liquid crystals for triggered release of bioactives.

In this review we present recent progress on lyotropic liquid crystals (LLC) as delivery vehicles for cosmetoceuticals, nutraceuticals, and drugs. LLC have been known for decades and their potential as delivery vehicles is well recognized. Yet, the two major mesophases, reverse hexagonal (H(II)) and bicontinuous cubic (primitive, gyroid, and diamond), are relatively hard gels with very slow release kinetics of the bioactives.

Structural behavior and interactions of dendrimer within lyotropic liquid crystals, monitored by EPR spectroscopy and rheology.

Micro- and macrostructural behaviors of three different lyotropic liquid crystals (LLCs) loaded with a dendrimer, namely second generation poly(propylene imine) (PPI-G2), were studied by means of rheology and electron paramagnetic resonance (EPR). The three mesophases were L(α), Q(224), and H(II) composed of glycerol monooleate (GMO) and water-PPI-G2 solution (and d-α-tocopherol (vitamin E) in the case of H(II)). We characterized the impact of PPI-G2 interactions with the components of the host mesophases on their structural characteristics on different length scales.

Penetratin-induced transdermal delivery from H(II) mesophases of sodium diclofenac.

Penetratin, a cell penetrating peptide is embedded within a reversed hexagonal (H(II)) mesophase for improved transdermal delivery of sodium diclofenac (Na-DFC). The H(II) mesophase serves as the solubilization reservoir and gel matrix whereas penetratin is the transdermal penetration enhancer for the drug. The systems were characterized and the interactions between the components were determined by SAXS, ATR-FTIR and SD-NMR.

Complex dendrimer-lyotropic liquid crystalline systems: structural behavior and interactions.

The incorporation of dendrimer into three lyotropic liquid crystalline (LLCs) mesophases is demonstrated for the first time. A second generation (G2) of poly(propylene imine) dendrimer (PPI) was solubilized into lamellar, diamond reverse cubic, and reverse hexagonal LLCs composed of glycerol monooleate (GMO), and water (and D-α-tocopherol in the H(II) system). The combination of PPI with LLCs may provide an advantageous drug delivery system.

Sodium diclofenac and cell-penetrating peptides embedded in H(II) mesophases: physical characterization and delivery.

Glycerol monooleate (GMO)-based mesophases offer extensive prospects for incorporation of various bioactive molecules. This work deals with the solubilization of selected cell-penetrating peptides (CPPs) together with sodium diclofenac (Na-DFC) within the H(II) mesophase for transdermal applications. The effect of CPPs such as RALA (an amphipatic CPP), penetratin (PEN), and oligoarginine (NONA) on Na-DFC skin permeation kinetics to provide controlled release and tune the drug transdermal diffusion was studied.

Type and location of interaction between hyperbranched polymers and liposomes. Relevance to design of a potentially advanced drug delivery nanosystem (aDDnS).

Advanced drug delivery nanosystems (aDDnSs) combining liposomal and dendritic materials have only recently appeared in the research field of drug delivery. The nature and localization of the interactions between the components of such systems are not yet fully described. In this study, liposomes are combined with hyperbranched polyesters for the development of new aDDnSs.

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 (H(II)) of monoolein/water were not widely subjected to practical applications since these were stable only at elevated temperatures.

Solubilization of gabapentin into HII mesophases.

In the present work, we report on the solubilization of gabapentin (GBP) into lyotropic hexagonal mesophases composed of monoolein, tricaprylin, and water. It was demonstrated that the hexagonal structure remained intact up to 2 wt % gabapentin, whereas the lamellar phase coexisted with the hexagonal one in the concentration range of 3-4 wt % of the drug. At gabapentin content of 5-6 wt %, only lamellar phases containing defects such as dislocations and multilamellar vesicles were detected.

Solubilization of a dendrimer into a microemulsion.

The present work investigates, for the first time, a system comprising a dendrimer incorporated into the water core of water-in-oil (W/O) microemulsion (ME). A second generation (G-2) poly(propyleneimine) dendrimer (PPI) was solubilized into W/O ME composed of AOT (sodium bis(2-ethylhexyl)sulfosuccinate), heptane, and water. Such a model system possessing the benefits of both dendrimers and ME, can potentially offer superior control of drug administration.

Influence of cyclosporine A on molecular interactions in lyotropic reverse hexagonal liquid crystals.

We present a dielectric study of H(II) mesophases (H(II)) based on a GMO/tricaprylin/phosphatidylcholine/water system seeded with the peptide Cyclosporine A (CSA). The study covers a frequency range 0.01 Hz to 1 MHz and a temperature range of 293 to 319 K, with a 3 K temperature step.

In vitro permeation of diclofenac salts from lyotropic liquid crystalline systems.

In this paper we examined feasible correlations between the structure of different lyotropic mesophases and transdermal administration of three diclofenac derivatives with varying degrees of kosmotropic or chaotropic properties, solubilized within the mesophases. It was found that the most chaotropic derivative of diclofenac diethyl amine (DEA-DFC) interacted with the polar heads of glycerol monooleate (GMO), thus expanding the water-lipid interface of the lamellar and cubic mesophases. This effect was detected by an increase in the lattice parameter of both mesophases, enhanced elastic properties, and increased solid-like response of the systems in the presence of DEA.

Temperature-dependent behavior of lysozyme within the reverse hexagonal mesophases (H(II)).

This manuscript is the second part of a study on the structural behavior of lysozyme-loaded reverse hexagonal mesophases. In the current paper we focused mainly on the mutual temperature-dependency relationship between the protein and the mesophase. The conformational stability of the enzyme and the structural effects on the host system were characterized using small-angle X-ray scattering (SAXS), ATR-FTIR spectroscopy, fluorescence, and rheological measurements.

Lysozyme entrapped within reverse hexagonal mesophases: physical properties and structural behavior.

A model protein (lysozyme) was incorporated into monoolein-based reverse hexagonal (H(II)) mesophase and its structure effects were characterized by small angle X-ray scattering, ATR-FTIR spectroscopy, and rheological measurements. Modifications in molecular organization of the H(II) mesophases as well as the conformational stability of lysozyme (LSZ) as a function of pH and denaturating agent (urea) were clarified. Up to 3 wt.

Molecular interactions in lyotropic reverse hexagonal liquid crystals: a dielectric spectroscopy study.

A dielectric study of reverse hexagonal mesophases (HII) is presented. Conducted in the frequency range 0.01-1 MHz and temperature range 293 View Article and Find Full Text PDF

Soft matter dispersions with ordered inner structures, stabilized by ethoxylated phytosterols.

This paper describes the formation and characterization of liquid crystalline dispersions based on the hexagonal phase of GMO/tricaprylin/water. As a stabilizer of the soft particles dispersed in the aqueous phase, a non-ionic, non-polymeric surfactant--ethoxylated phytosterol with 30 oxyethylene units (PhEO) was utilized. In contrast to Pluronic copolymers, normally utilized in the stabilization of liquid crystalline dispersions with ordered inner structure, use of such non-polymeric surfactant is not a common practice in this field.

Crystal structure of an inverting GH 43 1,5-alpha-L-arabinanase from Geobacillus stearothermophilus complexed with its substrate.

Arabinanases are glycosidases that hydrolyse alpha-(1-->5)- arabinofuranosidic linkages found in the backbone of the pectic polysaccharide arabinan. Here we describe the biochemical characterization and the enzyme-substrate crystal structure of an inverting family 43 arabinanase from Geobacillus stearothermophilus T-6 (AbnB). Based on viscosity and reducing power measurements, and based on product analysis for the hydrolysis of linear arabinan by AbnB, the enzyme works in an endo mode of action.

Concentration- and temperature-induced effects of incorporated desmopressin on the properties of reverse hexagonal mesophase.

In this paper we report on the solubilization of desmopressin, as a model for peptide drugs, into reverse hexagonal (H(II)) liquid crystals. Concentration- and temperature-induced interactions of desmopressin, as well as the conformation of the peptide, were studied using small-angle X-ray scattering, ATR-FTIR spectroscopy, SD-NMR, and rheological measurements. A considerable increase (up to 6 A) in the lattice parameter of the mesophases was obtained upon incorporation of the peptide.

Molecular interactions in reverse hexagonal mesophase in the presence of Cyclosporin A.

The present work investigates the detailed molecular structure of the H(II) mesophase of GMO/tricaprylin/phosphatidylcholine/water system in the presence of hydrophobic model peptide Cyclosporin A (CSA) via ATR-FTIR analysis. The conformation of the peptide in the hexagonal mesophase, as well as its location and specific interactions with the components of the carrier, were studied. Incorporation of phosphatidylcholine to the ternary GMO/tricaprylin/water system caused competition for water binding between the hydroxyl groups of GMO and the phosphate groups of the phosphatidylcholine (PC) leading to dehydration of the GMO hydroxyls in favor of phospholipid hydration.

From the microscopic to the mesoscopic properties of lyotropic reverse hexagonal liquid crystals.

In the present study we aimed to explore a correlation between the microstructural properties of the lyotropic reverse hexagonal phase (HII) of the GMO/tricaprylin/phosphatidylcholine/water system and its mesoscopic structure. The mesoscopic organization of discontinuous and anisotropic domains was examined, in the native state, using environmental scanning electron microscopy. The topography of the HII mesophases was imaged directly in their hydrated state, as a function of aqueous-phase concentration and composition, when a proline amino acid was solubilized into the systems as a kosmotropic (water-structure maker) guest molecule.

An HII liquid crystal-based delivery system for cyclosporin A: physical characterization.

In the present study we demonstrate that large quantities of cyclosporin A and three dermal penetration enhancers (phosphatidylcholine, ethanol, or Labrasol) can be solubilized into reverse hexagonal (HII) liquid crystalline structures composed of monoolein, tricaprylin, and water. The microstructural characteristics of these complex multi-component systems were elucidated by rheological, SAXS, and DSC measurements. Addition of up to 20 wt% phosphatidylcholine improved significantly the elastic properties of the systems (lower values of tandelta) and increased the thermal stability of the mesophases enabling us to solubilize up to 6 wt% cyclosporin A and two other enhancers (Labrasol and ethanol) to obtain stable mesophases at physiological temperature.