Lamellar Gel Research Articles

Ocular lamellar crystalline gels for sustained release and enhanced permeation of resveratrol against corneal neovascularization

Corneal neovascularization (CNV) is the major cause of blindness after eye injury; however, only several drugs can be applied and the invasive administration ways (i.e., intravitreal injection and subconjunctival injection) are used. Resveratrol is a highly effective anti-VEGF agent against CNV. However, its applications are limited due to its strong hydrophobicity and instability. Here, we developed a resveratrol-loaded ocular lamellar crystalline gel (ROLG) for high inhibition of CNV. ROLGs were composed of resveratrol, glyceryl monooleate (GMO), ethanol, and water, and their lamellar crystalline structures were identified by polarizing light microscopy and small-angle X-ray scattering. High drug loading (4.4 mg/g) of ROLGs was achieved due to the hydrogen bonding between GMO and resveratrol. Resveratrol showed sustained release with 67% accumulative release in 7 h, which was attributed to the slow erosion of gels. Resveratrol in ROLGs had a high corneal permeation 3 times higher than resveratrol in hyaluronic acid suspensions (RHSs). ROLGs were administered to rats only once a day because of their strong retention on the cornea surface. ROLGs were safe due to the very little contact of ethanol in ROLGs to the cornea. CNV post-rat corneal alkaline injury was highly inhibited by ROLGs, resulting from the attenuation of corneal VEGF expression and then corneal healing was improved. The ROLG was a promising ocular medicine for the prevention of CNV.

Structural properties of cationic surfactant-fatty alcohol bilayers: insights from dissipative particle dynamics.

Bilayers, self-assembled by cationic surfactants and fatty alcohols in water, are the basic units of lamellar gel networks - creamy formulations extensively used in cosmetics and pharmaceutics. Mesoscopic modelling and study of the bilayers formed by single- or double-tail cationic surfactants (CTAC or DHDAC), and fatty alcohols (FAs) in the lamellar fluid and gel phases were employed. Fatty alcohols with alkyl tail equal to or greater than the surfactant alkyl tail, i.e., C16FA or C18FA and C22FA, were considered. A model formulation was explored with the FA concentration greater than that of the surfactant and the structure of the fluid and gel bilayers in tensionless state characterised via the density profiles across the bilayers, orientational order parameters of the surfactant and FA chains, intrinsic analysis of the bilayer interfaces, and bending rigidity. The intrinsic analysis allows identification and quantification of the coexistence of the interdigitated and non-interdigitated phases present within the gel bilayers. The FA chains were found to conform the primary scaffolding of the bilayers while the surfactant chains tessellate bilayer monolayers from their water-hydrophobic interface. Further, the overlap of the FA chains from the apposed monolayers of the fluid bilayers rises with increasing FA length. Finally, the prevalence of the non-interdigitated phase over the interdigitated phase within the gel bilayers becomes enhanced upon the FA length increase with a preference of the surfactant chains to reside in the non-interdigitated phase rather than the interdigitated phase.

Unexpected observation of an intermediate hexagonal phase upon fluid-to-gel transition: SDS self-assembly in glycerol

Understanding morphological transformations upon temperature-induced mesophase transitions offers mechanistic insights into the self-assembly process. We have recently reported the unexpected formation of a microfibrillar lamellar gel in SDS-glycerol mixtures above a critical gelation concentration (CGC) as low as ~2 wt%. The gel phase comprised a fibrillar structure on the microscale and a lamellar structure on the nanoscale. Here, the nanoscopic structure of the gel as a function of temperature was probed with small-angle neutron scattering (SANS). The gel underwent a gel-to-fluid transition at a critical gelation temperature, TGC = 45 °C, forming cylindrical micelles at elevated temperatures. Upon cooling, a hexagonal phase formed at ~TGC, evident from the SANS Bragg peaks. This hexagonal phase upon the fluid-to-gel transition sheds light on the gelation mechanism, in which self-assembled SDS micelles undergo a cylindrical-to-lamellar morphological transition via a hexagonal phase. This unprecedented observation also highlights the complexity of self-assembly in nonaqueous hydrogen-bonding rich media.

Stabilization of vitamin C in emulsions of liquid crystalline structures

Emulsified systems are widely used for topical delivery with the aim of optimizing cutaneous absorption and offering a pleasant sensory. They also may provide a protection of the active molecule against oxidation and/or degradation. The oil phase of o/w emulsions may consist of liquid crystalline structures, especially lamellar structures which are similar to those found in the stratum corneum lipids. In the present work, o/w emulsions containing liquid crystals of mixed cetyl alcohol and Polysorbate 60 were developed for topical delivery of vitamin C, a potent antioxidant with several applications in the cosmetic and pharmaceutical fields. In addition to the well-documented lipid supplementation of the stratum corneum, the liquid crystal emulsions provide a significant chemical stabilization of vitamin C against its degradation. Emulsions were characterized by X-ray diffraction, polarized optical microscopy, and transmission electron microscopy. The stability of vitamin C in the formulations was evaluated upon storage in different conditions of temperature. The emulsions contain a complex colloidal structure, consisting of lamellar liquid crystalline (Lα) and crystalline lamellar gel (Lβ) phases, that provide a very efficient protection of vitamin C against its degradation.

Rheological fingerprinting as an effective tool to guide development of personal care formulations

Conventional rheological techniques in the linear viscoelastic region provide insights about the spatial configuration of the microstructural components of personal care formulations in their 'at-rest' state. However, they fail to describe the textural experience associated with large and fast deformations during daily consumer application. In this study we present a non-conventional rheological technique-large amplitude oscillatory shear (LAOS)-for probing the transformation of a material during its application. This technique is proposed a practical tool for formulators in their efforts to design products with desired textural attributes. A non-linear rheological technique termed LAOS was utilized to capture the textural expression perceived by consumers. Lissajous plots (stress vs. strain or strain rate) provide a fingerprint of the formula and are utilized to both analyse the thickening mechanism and monitor the influence of various parameters, such as the chemistry, molecular properties, colloidal parameters and processing conditions. In this study, we showcased several approaches for modifying the texture of personal care formulations and show the influence of various parameters on the characteristics of the Lissajous curves and their relation to sensorial perception. This fingerprinting technique shows that increasing the molecular weight or hydrophobic modification boosts the elasticity and thickening efficiency of a given polymer. Differences in the chemistry of rheological ingredients also influence the characteristic Lissajous fingerprint. In high concentration surfactant systems, which tend to form worm-like micelles, their unique Lissajous fingerprints indicate structure rebuild because of fast kinetics at large but slow deformations. Analysis of lamellar gel-based hair conditioner formulations demonstrates the unique high yield stress of these types of materials, accompanied by the fast breakdown transition from a solid to viscous structure because of their crystalline lamellar gel structure. The LAOS technique presented in this article is intended to better capture the textural expression perceived by consumers. Lissajous plots-generated from the LAOS experimental data-provide a fingerprint of the tested formula and are utilized to both analyse the thickening mechanism and monitor the influence of various parameters, such as the chemistry and molecular weight of the thickener, pH of the formula medium and influence of other ingredients in the formula (surfactants, emulsifiers, etc.).

Characterizing the rheology, slip, and velocity profiles of lamellar gel networks

The authors report the rheology and shear flow velocity profiles of pseudo-ternary “lamellar gel networks” commonly found in cosmetic emulsions such as creams, lotions, and hair conditioners, consisting of the cationic surfactant behentrimonium methosulfate, a fatty alcohol mixture of cetyl and stearyl alcohol, and water at surfactant/fatty alcohol mole fractions ranging from 0.1 to 0.6 and water mass fractions of 85%–97%. The high shear-thinning viscosity shows hysteresis in up- and down-ramps of the shear rate, with the gel “remembering” its highest shear for around 12 h before it heals and recovers its original viscosity. These materials exhibit rheological signatures characteristic of a soft glassy material (as described by the soft glassy rheology model) such as shear hysteresis, inhomogeneous velocity gradient, a solidlike creep response, power-law stress decay in step strain experiments, and high storage modulus relative to loss modulus over a wide range of frequencies, confirming its nearly elastic response for small deformations. Using particle image velocimetry (PIV) in steady shear experiments, a transition from a linear velocity profile to a pluglike profile was observed at shear rates above around 0.01 s−1. PIV also revealed macroscopic inhomogeneities including the development of fracture planes and shear bands, with rheology becoming gap-dependent and displaying some characteristics of solidlike friction.

Microstructure design of CTAC:FA and BTAC:FA lamellar gels for optimized rheological performance utilizing automated formulation platform.

The main objective of this paper was to optimize hair conditioner performance through variation of composition utilizing automated cosmetic formulation platform and advanced characterization techniques as well as develop understanding of how performance (wet combing and wet lubrication) of hair conditioner is affected by its rheology (i.e. yield stress) and controlled breakdown of the formulations (dilution). The experimental results show that yield stress greatly impacts rheology, stability and performance of the lamellar gels for hair conditioning. All samples were prepared on the Chemspeed Flex Formax. A mechanical rheometer was used to measure bulk viscosity and yield stress in each sample. Dia-stron tensile tester was used to measure the lamellar gels ability to reduce combing force. Potential stronger lamellar gel network formation in the formed lamellar gels potentially leads to higher yield stress exhibited. Viscosity values were also measured after a controlled breakdown (i.e. dilution) of each sample. This was also carried out using a mechanical rheometer. Yield stress of the formulations was engineered through composition variation and was recorded in each system. The highest yield stress value is 251.179Pa at a BTAC/CA ratio of 6:10, and the lowest yield stress is 50.14Pa at a BTAC/CA ratio of 6:5. The highest yield stress value is 50.14Pa at a CTAC/CA ratio of 6:10, and the lowest yield stress is 19.98Pa at a CTAC/CA ratio of 2:10. The highest overall yield stress values can also be observed in the BTAC/CA system, whereas the CTAC/CA system has relatively lower yield stress values. Dilution of each formulation caused a breakdown in viscosity of each formulation with the formulations with highest yield stress maintaining higher viscosity than the other formulations. The formulations with highest yield stress in each system which also maintains the highest dilution viscosity (6% BTAC/10% CA and 6% CTAC/10% CA) have the best effect on reducing overall combing force, that is from dry hair tress to wet hair tress and after product is rinsed off. At a BTAC/CA system of ratio 6:5, there is an 89% reduction in combing force and a 95% reduction in combing force in the BTAC/CA system of ratio 6:10. At a CTAC/CA system of ratio 2:10, there is a 65% reduction in combing force and a 88% reduction in combing force in the CTAC/CA system of ratio 6:10. A 'conditioned' soft feel was observed on each hair tress as the sample was applied and after it was rinsed off. The overall performance of the lamellar gels for hair conditioning can be engineered through optimization of the formulation microstructure and formulation microstructure breakdown on dilution.

The curious case of SDS self-assembly in glycerol: Formation of a lamellar gel

HypothesisHydrogen-bonding capacities of polar nonaqueous media significantly affect self-assembly behaviours of surfactants in these media. IntroductionGlycerol, a nonaqueous hydrogen-bonding solvent, is widely used in industrial formulations due to its desirable physical properties. Surfactants are ubiquitous in such applications; however, surfactant self-assembly in glycerol is not well understood. MethodsThe microscopic structure of the gel phase was studied using a series of imaging techniques: polarised light microscopy (PLM), confocal laser scanning microscopy (CLSM), and environmental scanning electron microscopy (ESEM). The rheological properties of the gel were studied using viscometry and oscillation rheology measurements. Further nano-structural characterisation was carried out using small-angle neutron scattering (SANS). ResultsWe have observed the unexpected formation of a microfibrillar gel in SDS and glycerol mixtures at a critical gelation concentration (CGC) as low as ~2 wt%; such SDS gelation has not been observed in aqueous systems. The microscopic structure of the gel consisted of microfibres some mm in length and with an average diameter of D ~ 0.5 μm. The fibres in the gel phase exhibited shear-induced alignment in the viscometry measurements, and oscillation tests showed that the gel was viscoelastic, with an elastic-dominated behaviour. Fitting to SANS profiles showed lamellar nano-structures in the gel microfibres at room temperature, transforming into cylindrical-micellar solutions above a critical gelation temperature, TCG ~ 45 °C. ConclusionsThese unprecedented observations highlight the markedly different self-assembly behaviours in aqueous and nonaqueous H-bonding solvents, which is not currently well understood. Deciphering such self-assembly behaviour is key to furthering our understanding of self-assembly on a fundamental level.

Comparative studies on structure and physiochemical changes of millet starch under microwave and ultrasound at the same power

As two novel starch modification technologies, the comparative study between microwave (MC) and ultrasound (UC) is of important significance for their applications. The objective of this work is to compare the changes of millet starch with MC and UC, focusing on the viscosity, swelling power (SP), transparency (TR), short-range molecular order (FT-IR spectrum), thermal properties (DSC), long-range molecular order (X-ray diffraction), in vitro enzymatic digestibility, and morphological properties. MC changed the type of the pasting curves form B-type to C-type, and the maximum decrease of the peak viscosity and relative crystallinity of MC starch was 74.9% and 100%, however, these changes for UC starch were only 14.8% and 23.2%. MC decreased the SP, TR, DSC, and ratio of absorbances at 1047/1022 cm−1, but UC caused opposite trend of these properties. Both MC and UC increased the in vitro enzymatic digestibility by 26.7% and 13.3%, respectively. MC also destroyed the original appearance of the starch granules and formed smaller and lamellar gel blocks. In conclusion, MC had greater influence on starch structure and properties than UC, even in a short period.

Effect of the Crystallization Process of Surfactant Bilayer Lamellar Structures on the Elongation of High-Aspect-Ratio Gold Nanorods.

The growth mechanism of an "in-gel synthesis method", that is, the effects of composition and structure of the lamellar gel phase below the Krafft temperature of surfactant solutions on the growth of long gold nanorods, was investigated. We changed the alkyl chain length of surfactant molecules to investigate the effect of surfactant self-assembly on the elongation of gold nanorods systematically; eight mixed solutions of alkyltrimethylammonium bromide (C nTAB; n = 2-16; n = even) with C18TAB were used for investigation. The Krafft temperature, self-assembly of surfactant molecules, and the crystallization process of each mixture were observed by differential scanning calorimetry, wide-angle X-ray scattering, visual inspection, and small-angle X-ray scattering. Gold nanorods were synthesized in these eight surfactant mixtures. These observations demonstrated that when the surfactant Lβ phase sustains for a long time, the space of the water layer is also kept large enough for the seeds to take up Au ions bound to surfactant micelles. In this case, the seeds can form long nanorods between bilayers. We conclude that not only the stability of the lamellar gel phase but also co-existence of Au-ion carriers, that is, surfactant micelles, is essential for the elongation of long gold nanorods.

A Thermally Stable Polyamine/Unsaturated Fatty Acid System: Gelation Behaviors and Application

AbstractThe gelation behavior of diethylenetriamine (DETA) and oleic acid (OLA) with different molar ratios in water was investigated. The gels, which were composed of lamellar phase and vesicles, were characterized using small‐angle X‐ray scattering (SAXS) and freeze‐fracture transmission electron microscopy (FF‐TEM). The responsive rheological properties were also investigated. Our results show that lamellar gels and rodlike micelles were formed successively with the increase of the DETA/OLA molar ratio. The lamellar gels exhibiting high thermal stability can be obtained in a wide range of polyamine/unsaturated fatty acid molar ratios. The mechanism of lamellar gel formation was explained by the packing parameter and the noncovalent interactions between the building blocks. Moreover, gel–sol transition can be triggered by tuning pH and ionic strength. This system has a good emulsification property, and no obvious nanoemulsion droplet coarsening is observed upon dilution after 30 days.

Physicochemical characterization of 6-O-acyl trehalose fatty acid monoesters in desiccated system

The understanding of the basic physicochemical properties of trehalose lipid is indispensable to extending their availability. In this study, the hydrate crystal (Cr), the liquid crystalline (LC) phase and the glassy state formations of 6-O-acyl trehalose fatty acid monoester (TREn) were examined under in a desiccated system. TREn (n = 10, 12, 14, 16) formed monohydrate Cr and showed the hydrate Cr-glassy fluid lamellar LC (Lα) phase transition via dehydration in the heating process. Here, Lα phase for TRE10 and TRE12 was kinetically formed by the dehydration below the glass transition temperature (Tg). On the dehydration temperature (Tdeh), Tgs, and heat capacity changes (ΔCps) at these Tgs, no distinct effects by the difference of the acyl chain length were recognized, possibly because the core structure of containing sugar hydrate Cr or sugar moieties should be similar regardless of the acyl chain length. Besides, TRE10 having a relatively high hydrophilic/hydrophobic balance (HLB) afforded to form the cubic LC (Q) phase and the corresponding glassy phase, while TRE14 and TRE16 having low HLB afforded the Lα phase as well as the corresponding glassy phases above Tg. TRE12 having middle HLB afforded both LCs and the corresponding glassy phase by controlling the kinetics of LC-LC phase transition between Lα and Q phases. Furthermore, the anomalous reversible phase transition during both the heating and cooling processes was also ascertained in the glassy phase for TRE16, which was considered the phase transition between glassy Lα and glassy lamellar gel (Lβ) phase. It greatly empathizes the two-dimensional trehalose glass layer and fluid hydrocarbon chains in the TREn glassy phase. Thus, in this study, it was demonstrated that TREn as the simplest trehalose lipid exhibited the glassy formation performance as well as the hydrate Cr formation, which showed less chain length dependence, together with the LC formation and the phase transition between glassy Lα and glassy Lβ phase, which depended on chain length greatly.

Effect of Tumor Relevant Acidic Environment in the Interaction of a N-hydroxyindole-2-Carboxylic Derivative with the Phospholipid Bilayer.

The inhibitors of the human isoform 5 of lactate dehydrogenase (hLDH5) have attracted growing interest as efficient anti-cancer agents. In the present paper, the interactions between an efficient hLDH5 inhibitor (N-hydroxyindole-2-carboxylic derivative) and lipid bilayers based on dipalmitoylphosphatidylcholine (DPPC) were investigated. Additionally, since interstitial acidification plays a key role in tumor pathogenesis and tumor drug therapy, the effect of acidic pH was assessed and correlated to DPPC/drug interaction. Four different techniques were used: differential scanning calorimetry, dynamic light scattering, UV-VIS second derivative spectrometry and attenuated total reflection Fourier transformed infrared spectroscopy. All techniques concur in highlighting a structural change of lipid assembly, susceptible both to pH change and to the presence of the antitumor compound. Lipid vesicles appeared more compact at the lower pH, since the thermal pre-transition from the lamellar gel phase to the ripple gel phase was absent at pH7.4 and the infrared analysis revealed a stronger acyl chain packing as well as a different hydration degree. Drug interaction was mainly detected in the lipid region including the ester linkages and the first portion of the acyl chains. Furthermore, a lower drug partitioning was recorded at pH6.6. The investigated antitumor agent possesses a stable negative charge at the investigated pH values, thus the lower interaction at the acidic pH is mainly ascribable to an environmental effect on lipid assembly. Therefore, drug efficacy under tumor acid conditions may be hampered by the observed lipid membrane constraints, and suggest for the development of suitable prodrugs.

Phase Behavior Controlled by the Addition of Long-Chain n-Alcohols in Systems of Cationic Surfactant/Anionic Polyion Complex Salts and Water.

Phase behavior of surfactants in water may be affected by the addition of a third component, and the present study discusses how long-chain n-alcohols affect phase transitions of systems formed by the surfactant hexadecyltrimethylammonium bromide, C16TAB, or its complex salts formed with polyacrylate, C16TAPA30, as well as other previously reported complex salts/water/alcohol systems. Structural characterization by X-ray diffraction patterns at small and wide angles and different temperatures was performed for samples containing n-decanol, n-dodecanol, or n-tetradecanol. Differential scanning calorimetry (DSC) was also used to study the phase transition. The results allowed us to observe and understand the coexistence of lamellar gel (Lβ) and lamellar liquid-crystal (Lα) phases, elucidating the structure of a previously reported mesophase, proposing an alternative assignment. Whereas the chain-melting transition is well-known to be sharp for lipids, we have found that it is broader for C16TAB and C16TAPA in the presence of these n-alcohols. We have investigated the effects of their composition and chain length on the temperature and enthalpy of transition. This elucidates why the addition of n-alcohols with chains slightly shorter than that of the surfactants leads to the formation of an ordered gel-like lamellar phase (Lβ). n-Alcohols act as neutral cosurfactants, leading to more packing, and all of the factors converge to a limit situation, associated with a common critical area occupied by each alkyl chain. We compared our results with other mesophase systems from the literature, demonstrating that the same trends of phase behavior occur for complex salts of other polyelectrolytes with alkyltrimethylammonium surfactants.

Impact of Headgroup Asymmetry and Protonation State on the Aggregation Behavior of a New Type of Glycerol Diether Bolalipid.

In the present work, we describe the synthesis and the temperature-dependent aggregation behavior of a new class of asymmetrical glycerol diether bolalipids. These bolalipids are composed of a membrane-spanning alkyl chain with 32 carbon atoms (C32) in the sn-3 position, a methyl-branched C16 alkyl chain in the sn-2 position, and a zwitterionic phosphocholine headgroup in the sn-1 position of a glycerol moiety. The long C32 alkyl chain is terminated either by a second phosphocholine (PC-Gly(2C16Me)C32-PC) or by a phosphodimethylethanolamine headgroup (PC-Gly(2C16Me)C32-Me2PE). The temperature- and pH-dependent aggregation behavior of both lipids was studied using differential scanning calorimetry (DSC), Fourier transform infrared (FTIR) spectroscopy, small-angle X-ray scattering (SAXS), and small-angle neutron scattering (SANS) experiments. The morphology of the formed aggregates in an aqueous suspension was visualized by transmission electron microscopy (TEM). We show that PC-Gly(2C16Me)C32-PC and PC-Gly(2C16Me)C32-Me2PE at pH 5 self-assemble into large lamellar aggregates and large lipid vesicles. Within these structures, the bolalipid molecules are probably assembled in a monolayer with fully interdigitated chains. The lipid molecules seem to be tilted with respect to the layer normal to ensure a dense packing of the alkyl chains. A temperature increase leads to a transition from a lamellar gel phase to the liquid-crystalline phase at about 28-30 °C for both bolalipids. The lamellar aggregates of PC-Gly(2C16Me)C32-Me2PE started to transform into nanofibers when the pH value of the suspension was increased to above 11. At pH 12, these nanofibers were the dominant aggregates.

Effect of Hydrophobic Modification on the Properties of Polymer‐Blended Microemulsion Gels

AbstractPhase behavior of sodium oleate (NaOl)/isoamyl alcohol‐based lamellar gel phase in cedar oil/water medium in the presence of the nonionic polymer hydroxyethyl cellulose (HEC) and its hydrophobic modified product (HMHEC) is investigated for the development of polymer‐embedded surfactant gels. HMHEC is more soluble in oil‐in‐water (o/w) microemulsions, but nonionic HEC shows limited solubility in the lamellar microemulsion (o/w type). Quantitative estimation of rate of adsorption of the polymer on lamellae bilayers can be easily done by Sudan solubilization and methylene blue complexation methods. Addition of HMHEC to the lamellar gel phase increases the polymer solubilization limit of lamellar gels as well as the viscoelasticity and thermal stability. The polymer‐embedded microemulsion gel acts as a “clean gel” since it exhibits good solubilization in different hydrocarbon media at ambient conditions. Elastic modulus of the polymer‐embedded gel influences directly the suspension performance of gels at high temperature and yields a reasonable sand‐settling velocity acceptable according to fracturing standards. The thermal characteristics and viscoelastic properties of polymer‐embedded gel were found to be suitable for moderate‐temperature reservoir stimulation where the bottom hole temperature is in the range 70–75 °C. Already a large amount of experimental data on pure microemulsions (without polymer) exists. Our studies indicate that the developed polymer‐embedded microemulsion gel has great potential as a model system for the study of polymer–microemulsion interactions.

Effects of preparation processes on the structure and properties of collagen gel

ABSTRACTIn this study, the effects of collagen self-assembly, drying methods, and reswelling on collagen gel structure and biological properties were determined. The results showed that the self-assembly of collagen improved the regularity and pore size of the collagen gel and promoted collagen gel thermostability and cell proliferation. After drying and reswelling, the main structure of the self-assembly gel was composed of lamellar gel walls, but the gel structure shrank to some extent and pore size was reduced. The structure of the self-assembled gel after drying and reswelling was closely related to that of the drying method.

Ligand partitioning into lipid bilayer membranes under high pressure: Implication of variation in phase-transition temperatures

The variation in phase-transition temperatures of dipalmitoylphosphatidylcholine (DPPC) bilayer membrane by adding two membrane-active ligands, a long-chain fatty acid (palmitic acid (PA)) and an inhalation anesthetic (halothane (HAL)), was investigated by light-transmittance measurements and fluorometry. By assuming the thermodynamic colligative property for the bilayer membrane at low ligand concentrations, the partitioning behavior of these ligands into the DPPC bilayer membrane was considered. It was proved from the differential partition coefficients between two phases that PA has strong affinity with the gel (lamellar gel) phase in a micro-molal concentration range and makes the bilayer membrane more ordered, while HAL has strong affinity with the liquid crystalline phase in a milli-molal concentration range and does the bilayer membrane more disordered. The transfer volumes of both ligands from the aqueous solution to each phase of the DPPC bilayer membrane showed that the preferential partitioning of the PA molecule into the gel (lamellar gel) produces about 20% decrease in transfer volume as compared with the liquid crystalline phase, whereas that of the HAL molecule into the liquid crystalline phase does about twice increase in transfer volume as compared with the gel (ripple gel) phase. Furthermore, changes in thermotropic and barotropic phase behavior of the DPPC bilayer membrane by adding the ligand was discussed from the viewpoint of the ligand partitioning. Reflecting the contrastive partitioning of PA and HAL into the pressure-induced interdigitated gel phase among the gel phases, it was revealed that PA suppresses the formation of the interdigitated gel phase under high pressure while HAL promotes it. These results clearly indicate that each phase of the DPPC bilayer membrane has a potential to recognize various ligand molecules.

Development of lamellar gel phase emulsion containing baru oil (Dipteryx alata Vog.) as a prospective delivery system for cutaneous application

The rational design of emulsions requires study of the main factors that influence their formation, physicochemical properties and, consequently, stability and performance. The use of vegetable oils in the pharmaceutical and cosmetic industries has recently become attractive. Dipteryx alata Vogel (D. alata) is an oleaginous species native to Brazil. The seeds of this species contain highly unsaturated oil with significant amounts of tocopherols and phytosterols, representing an important source of agents capable of combatting oxidative processes. In this work, a lamellar gel phase emulsion using oil extracted from the seeds of D. alata (baru) was developed. The steps involved in the development of this research were as follows: 1) development of formulations and 2) in vitro assays by simulating the evaporation of the final product after application to the skin and Electron paramagnetic resonance spectroscopy (EPR) of fatty acid spin labels was used to investigate the profile of interaction of the dispersed systems with stratum corneum (SC) lipids. The results indicate that the developed system shows no signs of instability during the storage period. Moreover, EPR studies indicated that D. alata oil and especially the developed formulation were able to increase SC lipid fluidity and extract a fatty-acid spin label from the lipid domain structures of SC, demonstrating its potential to act as a drug or skin care vehicle.

Flexibility vs rigidity of amphipathic peptide conjugates when interacting with lipid bilayers

For the first time, the photoisomerization of a diarylethene moiety (DAET) in peptide conjugates was used to probe the effects of molecular rigidity/flexibility on the structure and behavior of model peptides bound to lipid membranes. The DAET unit was incorporated into the backbones of linear peptide-based constructs, connecting two amphipathic sequences (derived from the β-stranded peptide (KIGAKI)3 and/or the α-helical peptide BP100). A β-strand-DAET-α-helix and an α-helix-DAET-α-helix models were synthesized and studied in phospholipid membranes. Light-induced photoisomerization of the linker allowed the generation of two forms of each conjugate, which differed in the conformational mobility of the junction between the α-helical and/or the β-stranded part of these peptidomimetic molecules. A detailed study of their structural, orientational and conformational behavior, both in isotropic solution and in phospholipid model membranes, was carried out using circular dichroism and solid-state 19F-NMR spectroscopy. The study showed that the rigid and flexible forms of the two conjugates had appreciably different structures only when embedded in an anisotropic lipid environment and only in the gel phase. The influence of the rigidity/flexibility of the studied conjugates on the lipid thermotropic phase transition was also investigated by differential scanning calorimetry. Both models were found to destabilize the lamellar gel phases.