Lamellar Liquid Crystalline Systems Research Articles

Innovative Mucoadhesive Precursor of Liquid Crystalline System Loading Anti-Gellatinolytic Peptide for Topical Treatment of Oral Cancer.

Current researches report an actual benefit of a treatment for oral cancer via inhibition of proteolytic matrix metallopro-teinases (MPP) with a peptide drug, called CTT1. However, peptides present poor oral bioavailability. Topical administration on oral mucosa avoids its passage through the gastrointestinal tract and the first-pass liver metabolism, but the barrier function of the oral mucosa can impair the permeation and retention of CTT1. The objective of this study is to incorporate CTT1 into a mucoadhesive precursor of liquid crystalline system (PLCS) as an interesting strategy for the topical treatment of oral cancer. PLCS consisting of oleic acid, ethoxylated 20 and propoxylated cetyl alcohol 5, polyethyleneimine (P)-associated chitosan (C) dispersion and CTT1 (FPC-CTT1) was developed and characterized by polarized light microscopy (PLM) and small-angle X-ray scattering (SAXS). In vitro permeation and retention across esophageal mucosa, In vitro cytotoxicity towards tongue squamous cell carcinoma cells, and in vivo evaluation of vascular changes using the chick embryo chorioallantoic membrane (CAM) model were performed. PLM and SAXS showed that FPC-CTT1acted as PLCS, because it formed a lamellar liquid crystalline system after the addition of artificial saliva. FPC-CTT1increased approximately 2-fold the flux of permeation and 3-fold the retention of CTT1 on the porcine esophageal mucosa. CTT1 does not affect cell viability. CAM tests showed that FPC preserved the blood vessels and it can be a safe formulation. These findings encourage the use of the FPC-CTT1 for topical treatment of oral cancer.

Phase diagrams of new lamellar liquid crystalline systems based on 2H NMR spectroscopy data

Lyotropic liquid crystals based on cetylpyridinium chloride (or bromide) and n-hexanol were examined by NMR spectroscopy. The partial molecule ordering, residual dipolar couplings as well as the conditions (component concentrations and temperatures) under which lamellar phases exist were determined.

Trans-resveratrol-loaded nonionic lamellar liquid-crystalline systems: structural, rheological, mechanical, textural, and bioadhesive characterization and evaluation of in vivo anti-inflammatory activity.

Resveratrol (Res) is a common phytoalexin present in a few edible materials, such as grape skin, peanuts, and red wine. Evidence has shown the beneficial effects of Res on human health, which may be attributed to its anti-inflammatory activity. However, the poor aqueous solubility of Res limits its therapeutic effectiveness. Therefore, the use of nanostructured delivery systems for Res, such as liquid-crystalline systems, could be beneficial. In this study, we aimed to develop, characterize, and determine the in vivo effectiveness of Res-loaded liquid-crystalline systems. Systems containing copaiba balsam oil, polyethylene glycol-40 hydrogenated castor oil, and water were designed. Results of polarized light microscopy, small-angle X-ray scattering, texture-profile analysis, and flow-rheology analysis showed that the Res-loaded liquid-crystalline system had a lamellar structure, textural and mechanical (hardness, compressibility, and adhesiveness) properties, and behaved as a non-Newtonian fluid, showing pseudoplastic behavior upon skin application. Furthermore, all liquid-crystalline systems presented bioadhesive properties that may have assisted in maintaining the anti-inflammatory activity of Res, since the topical application of the Res-loaded lamellar mesophase liquid crystals resulted in edema inhibition in a carrageenan-induced paw-inflammation mouse model. Therefore, Res-loaded lamellar mesophases represent a promising new therapeutic approach for inhibition of skin inflammation.

Lamellar Liquid-Crystalline System with Tunable Iridescent Color by Ionic Surfactants.

Liquid crystals formed by the self-assembly of small molecules are very promising smart materials because of their unique properties, such as self-assembled multivalency, biocompatibility, and fast response to external stimuli. Here we report an iridescent liquid-crystal system composed of water layers, which is sandwiched by two bilayer membranes. Such membranes are composed of a self-assembled nonionic surfactant, which is called hexadecylglyceryl maleate (HGM), and only a small amount of ionic surfactants. It is found that the iridescent color of the liquid crystal system is very sensitive to the concentration of ionic surfactants, even if a trace of change of the ionic surfactants' concentration will induce the color change of liquid-crystal system. The result shows that with the increase in ionic surfactant concentration, the flat bilayer membrane tends to be curved to form some edge-dislocation defects. The appearance of such defects in the lamellar system leads to the decrease in spacing distance between adjacent bilayer membranes. This is because some vacant spaces emerged inevitably during this process. The ionic surfactant-sensitive HGM system also shows the thermal response. It is because the phase-separation results in the increase in local concentration of SDS in the bilayer membrane, which has the same effect as increasing the SDS concentration in the whole system.

Bioadhesive Surfactant Systems for Methotrexate Skin Delivery

Methotrexate (MTX) is an immunosuppressive drug for systemic use in the treatment of skin diseases, however, MTX presents a number of side effects, such as hepatotoxicity. To overcome this limitation, this study developed skin MTX delivery surfactant systems, such as a microemulsion (ME) and a liquid crystalline system (LCS), consisting of a glycol copolymer-based silicone fluid (SFGC) as oil phase, polyether functional siloxane (PFS) as surfactant, and carbomer homopolymer type A (C971) dispersion at 0.5% (wt/wt) as aqueous phase. Polarized light microscopy and small-angle X-ray scattering evidenced the presence of hexagonal and lamellar LCSs, and also a ME. Texture profile and in vitro bioadhesion assays showed that these formulations are suitable for topical application, showing interesting hardness, adhesiveness and compressibility values. Rheology analysis confirmed the Newtonian behaviour of the ME, whereas lamellar and hexagonal LCSs behave as pseudoplastic and dilatant non-Newtonian fluids, respectively. In vitro release profiles indicated that MTX could be released in a controlled manner from all the systems, and the Weibull model showed the highest adjusted coefficient of determination. Finally, the formulations were not cytotoxic to the immortalized human keratinocyte line HaCaT. Therefore, these bioadhesive surfactant systems established with PFS and C971 have great potential as skin delivery systems.

Rheological Characterization and Safety Evaluation of Non-Ionic Lamellar Liquid Crystalline Systems Containing Retinyl Palmitate.

Retinyl palmitate (RP) is widely used as a special interest ingredient in dermatological formulations to improve the elasticity of the skin and to reduce wrinkles by stimulating collagen synthesis. Nanotechnology-based drug delivery systems, such as liquid crystalline systems (LCSs), can modulate drug permeation into skin and improve the drug action. The effects of such systems on the skin, however, are not completely known. Possible undesirable effects of these formulations on the skin can be detected and interpreted by histopathology and histomorphometry. The objective of this study was to perform a rheological characterization to evaluate the safety of RP used in a lamellar LCS in vitro and in vivo. LCSs containing polyether functional siloxane as a surfactant, silicon glycol copolymer as an oil phase and water at ratios of 60:10:30 and 40:30:30, with (F₁v and F₂v, respectively) and without (F₁ and F₂ respectively) RP, were investigated. The rheological characterization was performed using steady shear rate sweep tests and dynamic frequency sweep tests carried out for up to 30 days for various storage temperature conditions (25 ± 2 °C, 37 ± 2 °C and 5 ± 2 °C). Cytotoxic effects were evaluated using J-774 mouse macrophages as a cellular model system. The in vivo tests were conducted on rabbits that had areas of skin treated as follows for 15 days: C (Control); F₁; F₁v; F₂; and F₂v. Histomorphometric and histopathological techniques were used to estimate the thicknesses of the epidermis and stratum corneum and the numbers of fibroblasts and leukocytes in the papillary dermis. Mean values were compared by ANOVA, followed by the Tukey test (p < 0.05). The steady shear rate sweep and dynamic frequency sweep tests confirmed the high viscosity of the LCS and the typical pseudo-plastic characteristic of the lamellar system. The RP-unloaded LCS and the RP-loaded LCS did not produce cytotoxicity, nor did they provoke significant thickening of the epidermis and stratum corneum. The number of leukocytes in the treated areas did not change; however, the number of fibroblasts in the area treated with F₁v was higher than in the areas treated with the control and F₂. The histological analyses demonstrated that none of the formulations irritated the skin and that formulation F₁v significantly increased the number of fibroblasts in the dermis, which could result in an increase in the production of collagen.

Director orientations in lyotropic liquid crystals: diffusion MRI mapping of the Saupe order tensor.

The macroscopic physical properties of a liquid crystalline material depend on both the properties of the individual crystallites and the details of their spatial arrangement. We propose a diffusion MRI method to estimate the director orientations of a lyotropic liquid crystal as a spatially resolved field of Saupe order tensors. The method relies on varying the shape of the diffusion-encoding tensor to disentangle the effects of voxel-scale director orientational order and the local diffusion anisotropy of the solvent. Proof-of-concept experiments are performed on water in lamellar and reverse hexagonal liquid crystalline systems with intricate patterns of director orientations.

Polyampholyte-tuned lyotrop lamellar liquid crystalline systems

The influence of a polyampholyte, i.e., poly(N,N′-diallyl-N,N′-dimethyl-altmaleamic carboxylate) (PalH), on the lamellar liquid crystalline (LC) system sodium dodecyl sulfate (SDS)/decanol/water was investigated by means of microdifferential scanning calorimetry, small-angle X-ray diffraction (SAXS), and cryo-scanning electron microscopy. After incorporating PalH into the lamellar liquid crystalline system, SAXS measurements show that three different LC phases exist: i.e., a swelling, slightly swelling, and non-swelling one. At pH 4, the positively charged polymer with an extended conformation can directly adsorb at the anionic head groups of the surfactant and more compact vesicles are formed at room temperature. At pH 9, the electrostatic interactions between the polyampholyte (in a more coiled conformation) and the sulfate head groups of the SDS are leveled off and incompact vesicles are formed at room temperature. That means in presence of the polyampholyte the morphology of the LC phase, i.e., the supramolecular vesicle structure, can be tuned by varying the pH and/or the temperature.

Structural characterization and in vivo evaluation of retinyl palmitate in non-ionic lamellar liquid crystalline system

Carrier systems for lipophilic drugs, such as the liquid crystalline systems (LCS) have been extensively studied to improve effect and selectivity. Retinyl palmitate (RP) is widely used in pharmaceutical and cosmetics products to improve the skin elasticity. The aim of this study was the development, characterization and the in vivo effectiveness of RP in non-ionic LCS structures. LCS containing polyether functional siloxane as oil phase, silicon glycol copolymer as surfactant and water in the ratio 30:10:60, with and without RP were studied. The results of the polarized light microscopy, small-angle X-ray scattering and rheology analysis indicated the presence of typical LCS structures with lamellar arrangement. Regardless of the presence of RP, the rheological studies showed the pseudo plastic behavior of the systems. However, highest hysteresis area was verified when comparing the system in the presence and in the absence of RP. Stability study SAXS monitored, carried out up to 30 days in various storage temperature conditions (25±2 °C, 37±2 °C and 5±2 °C) demonstrated the great structural stability of the LCS systems. The in vivo effectiveness analysis suggests that the RP-loaded LCS provided a significant reduction of the orbicular wrinkles in human volunteers (P=0.048).

Electrochemical Determination of Diffusion Anisotropy in Molecularly-Structured Materials

Theory is presented for the case of two-dimensional diffusion anisotropy in axiosymmetric systems, which, advantageously and indirectly, affords a unified theory of diffusive mass transport at planar, microdisk (or nanodisk) and cylindrical electrodes in isotropic media. A strategy is proposed to determine the extent of diffusion anisotropy in experimental data; proof-of-concept is considered via a lamellar lyotropic liquid crystalline system.

Molecular Dynamics Study of Poly(diallyldimethylammonium chloride) (PDADMAC)/Sodium Dodecyl Sulfate (SDS)/Decanol/Water Systems

We have performed a 50 ns of molecular dynamics study of poly(diallyldimethylammonium chloride) (PDADMAC)/sodium dodecyl sulfate (SDS)/decanol/water systems. The influence of the cationic polyelectrolyte on the anionic SDS-based lamellar liquid crystalline system was investigated. The main structural parameters have been calculated and compared with experimental data. We obtain two types of PDADMAC conformation, a more folded structure A and a structure B where the PDADMAC molecule is adsorbed at the anionic head groups of the surfactant molecules. The polyelectrolyte-induced coexistence of two lamellar phases at a concentration of 2-3% of PDADMAC is observed, which is in agreement with experimental findings.

Phase behavior and viscous properties of cetyltrimethylammonium bromide and sodium dodecyl sulfonate aqueous mixtures

Phase behavior of cetyltrimethylammonium bromide (CTAB)/sodium dodecyl sulfonate (AS)/water systems at 318.15 K with the total surfactant mole fraction x T ≤ 0.020 was investigated. In addition to the seven phase regions in the lower concentration range, two new phase regions, i.e. the hexagonal liquid crystalline phase region and its adjacent aqueous two-phase region were obtained in the higher concentration range. Shear viscosities of some isotropic single-phase systems, aqueous two-phase systems and lamellar liquid crystalline systems were measured. The experimental results indicate that at either isotropic single-phase region, under certain x T, there exists one shear viscosity maximum peak. As x T increases, the shear viscosity maximum peak shifts to the position far from the equimolar ratio of CTAB and AS, and meanwhile the value of the shear viscosity maximum peak increases. At each x T, the value of shear viscosity peak at the isotropic single-phase region with excess AS is less than that at the isotropic single-phase region with excess CTAB. The rheological behavior of the isotropic single-phase systems around the shear viscosity peak and that of lamellar liquid crystalline systems are complicated. Thixotropic, antithixotropic and complex thixotropic behaviors were all observed for these systems. Experimental results illustrate that both the isotropic single-phase systems and lamellar liquid crystalline systems located at position very close to the boundaries of the aqueous two-phase systems, as well as the coexisted phases in aqueous two-phase systems are not very viscous. When x T ≤ 0.005, their shear viscosities are usually several to dozens mPa s. In order to understand the rheological behaviors of the mixed systems, TEM micrographs of some isotropic single-phase systems and aqueous two-phase systems were investigated.

Effect of water-in-oil microemulsions and lamellar liquid crystalline systems on the precorneal tear film of albino New Zealand rabbits

The aim of this study is to investigate the effect of phase transition water-in-oil (w/o) microemulsions (ME) and liquid crystalline systems (LC) on the precorneal tear film (PCTF). The study used six albino NZ rabbits and monitored the integrity and stability of the PCTF before and after instillation of test formulations. The effects were evaluated by assessment of the PCTF lipid layer using interferometry, tear evaporation rate measurements, and indirect estimation of tear volume. Ocular application of test formulations changed the appearance of the PCTF lipid layer, indicating lipid layer disruption. The recovery time was longer in case of ME compared with an aqueous solution (SOL). The tear evaporation rate was increased after application of both ME and LC systems compared with the SOL, with the LC system showing the greatest effect. Tear volume measurement results revealed minimal changes associated with the instillation of both ME systems. Whilst phase transition w/o ME systems can interact with the PCTF lipid layer in albino New Zealand rabbits, their effect on the volume of resident tears was found to be minimal.

Relationship between Optical and Rheological Properties of Polymer-Added Lamellar Liquid-Crystalline Systems

Structural changes caused by polymer additives in lamellar liquid-crystalline systems have been studied by polarized microscopy and oscillatory rheology. Four ethoxylated fatty acid surfactants and two polymer additives (poly(ethylene oxide)−poly(propylene oxide)−poly(ethylene oxide)) were used. The parameters of a recently developed theoretical model were determined from the measured data. Values of the so-called orientation modulus (GE) were compared to the time of pseudoisotropy (tISO). Their change with the polymer content and polarity show the same tendency, which means that these essentially different parameters can be used in the same way for characterizing the elastic properties of such liquid-crystalline systems.

Structural properties of nonionic surfactant/glycerol/paraffin lyotropic liquid crystals

Lamellar lyotropic liquid-crystalline systems are thermodynamically stable, optically isotropic and are formed spontaneously. New possibilities for the development of controlled drug delivery systems are inherent in these systems in consequence of their stability and special, skin-friendly structure. The aim was to formulate and study two-component or multicomponent compositions with a relatively low Brij 96V content, liquid paraffin, glycerol and water for therapeutic purposes. The liquid crystals were examined by polarizing light microscopy and transmission electron microscopic observation of replicas produced by the freeze–fracture technique to demonstrate the presence of lamellar liquid-crystalline domains. The existence of a regular structure was determined by X-ray diffraction.

Structure and drug release of lamellar liquid crystals containing glycerol

Lamellar lyotropic liquid crystalline (LLC) systems are thermodynamically stable, optically isotropic systems, which are formed with low energy input. New possibilities for the development of controlled drug delivery systems are inherent in these systems due to their stability and special skin-similarly structure. The present aim was to formulate multicomponent LLC systems with a relatively low surfactant content, composed of materials official in the European Pharmacopoeia 4th. Polarizing light microscopic examination of the samples was carried out, together with TEM observation of replicas produced by freeze-fractured technique for the purpose of demonstrating the presence of lamellar LC domains. Our LLC samples contained: Brij 96 (poly-oxyethylene-10-oleyl ether) with water, liquid petrolatum (LP) and glycerol in a given concentration range. The interlamellar repeated distance ( d L) confirming the existence of a regular structure was determined by means of X-ray diffraction. The d L and G′values of the samples changed according to a maximum curve with increasing glycerol concentration up to 40% (w/w). A prolonged drug release was observed in case of the very water-soluble ephedrine hydrochloride and the same phenomena was observed in the case of tenoxicam, which is practically insoluble in water.

Polymerization of N,N-dimethylacrylamide in Aerosol OT–water mixtures: from lamellae to segregation

The polymerizable N,N-dimethylacrylamide (DMAA) is added to the lamellar liquid crystalline system formed by the anionic surfactant Aerosol OT and water. Small angle X-ray scattering, gives the same bilayer thickness and hydrophilic group cross-sectional area as without DMAA, and an environment sensitive fluorescent probe indicates that DMAA is likely to be in the water layers between the AOT bilayers. This shows that the structure of the AOT bilayer in the lamellar phase is not affected by DMAA. However, DMAA induces instability of the lamellar phase, and a second phase, an isotropic solution, appears for larger DMAA contents The effect of DMAA in stabilizing this phase with respect to lamellae is much larger than that expected from a simple dilution with water. Furthermore, there is a combined influence of temperature and DMAA concentration on the coexistence of the lamellar and the isotropic phases. When an initiator is added and the monomer polymerizes the tendency to phase separate increases strongly. The lamellar spacing after polymerization is below the value predicted by the global AOT/H2O ratio. This indicates that the polymer segregates from the AOT phase and that the lamellar phase is osmotically compressed by the polymer rich phase. (C) 2003 Elsevier Science B.V. All rights reserved.

Preparation of silver nanoparticles in liquid crystalline systems

Silver nanoparticles preparation and the aggregation stability of the particles was investigated in lamellar liquid crystalline systems. A liquid crystal of HDTABr/pentanol/water was first prepared. The water content was next increased while keeping the mass ratio of HDTABr and pentanol constant. Silver nanoparticles were produced by replacing the aqueous phase by Ag sols of various concentrations (0.5–5×10–3 mol/l) or by an in situ preparation method, i.e., interlamellar reduction of Ag+ ions in the liquid crystalline phase. The stability of the silver nanoparticles was monitored by UV-VIS spectroscopy and TEM. The particle size ranged from 5 to 44 nm. The kinetic of silver nanoparticle aggregation was investigated. The effect of nanoparticles on structural ordering in liquid crystals was studied by XRD measurements and it was established that the lamellar distance (dL) was only slightly altered.

Structural properties of cationic surfactant/pentanol/water systems and their interaction with negatively charged layer silicates

Hexadecyltrimethylammonium bromide/pentanol/water and hexadecylpyridinium chloride/pentanol/water liquid crystalline systems were investigated. We studied the influence of water and pentanol on the swelling and rheological properties of lamellar liquid crystalline systems. We studied the possibility of inserting negatively charged layer silicates in these cationic surfactant/pentanol/water systems. Combining the adsorption data from X-ray diffraction, the composition of adsorption layer was calculated. After addition of Na-montmorillonite to the liquid crystalline system, the silicate lamellae were built up into the ordered liquid crystalline structure. Therefore, in the case of adsorption from aqueous solution, ordered liquid crystalline structure appears in the adsorption space between the silicate layers, and this structure determines the degree of swelling and the adsorption layer composition on the solid silicate surface.

Polymeric Surfactants Based on Oleic Acid— Lamellar Liquid Crystal Polymerization of Sodium Oleate/Water/Hexadecane/4-Allyl-1, 6-Heptadiene-4-ol System And Sodium Oleate/Water/Hexadecane/Pentaerythritol Triarylate System

AbstractThe lamellar liquid crystalline (LLC) regions of sodium oleate (NaOL)/ water/hexadecane/4-allyl-1,6-heptadiene-4-ol (AHD-ol) system and sodium oleate (NaOL) /water/hexadecane/pentaerythritol triacrylate (PETA) system were determined when the weight ratio of NaOL to hexadecane was kept at 90:10. Copolymerization was accomplished in the LLC phases of the above systems. AHD-ol and PETA acted as the cross-linking agents between the double bonds on NaOL backbones in their systems respectively. Interlayer spacing determinations showed that the cross-linking agents, AHD-ol and PETA, were solubilized in the middle of the NaOL hydrocarbon chains in each LLC system. As a result, the copolymerization reactions were confined within each monolayer of the amphiphilic bilayer. The systems after the copolymerization were a mixture of water and LLC phase for the former system and a mixture of LLC phase and solid particles for the latter one. The aqueous solutions of copolymers exhibited surface activity, but with both higher CMC and surface tension values than NaOL aqueous solutions.