Binding and distribution of water molecules in DPPC bilayers doped with ß-sitosteryl sulfate.

We have comparatively studied the behavior of water molecules associated with the DPPC (1,2-dipalmitoyl-sn-glycero-3-phosphocholine) bilayers in the presence and absence of ß-sitosteryl sulfate (PSO4) with the help of differential scanning calorimetry (DSC) and SAXS (small-angle x-ray scattering) techniques. The DSC heating endotherms were analyzed to understand the intermolecular interactions between water molecules and the lipid headgroups. The strongly bound, weakly bound, and free water (SB-Water, WB-Water, and FW-Water, respectively) were thus identified in the bilayers and the impact of incorporating PSO4 was evaluated. The SAXS data provided the supporting evidence for the impact of PSO4 on the intake of water into the bilayer. Regardless of the presence or absence of PSO4, the SB-Water existed in the system as the non-freezable fraction. On the other hand, the WB-Water and FW-Water fractions, both of which are freezable, exhibited freezing and melting behaviors that differed from each other significantly. The enthalpies of fusion of the WB-Water, which differed from that of the FW-Water, also varied with the mole fractions of PSO4. PSO4 enhanced the fraction of WB -water in the bilayer while at the same time reducing the fractions of SB-Water and FW-Water. The optimum retainability and the ease of release of the available water makes this system efficient for maintaining skin homeostasis if used in cosmetic and pharmaceutical formulations.

Impact of Doping a Phytosteryl Sulfate on the Properties of Liposomes Made of Saturated and Unsaturated Phosphatidylcholines.

The size, dispersibility, and fluidity of DPPC (1,2-dipalmitoyl-sn-glycero-3-phosphocholine), POPC (1-palmitoy-2-oleoyl-sn-glycero-3-phosphocholine), and DOPC (1,2-dioleoyl-sn-glycero-3-phosphocholine) liposomes doped with ß-sitosteryl sulfate (PSO4) were comparatively studied. In all three types of liposomes, PSO4 reduced sizes and enhanced the negative values of the ζ-potential. However, the effect on sizes quantitatively differed in the three cases in a manner dependent on their phase behaviors. PSO4 rigidified each type of membrane in its liquid crystalline phase and fluidized the gel phase. It enhanced the glucose trapping efficiency (TE) of both DPPC and DOPC liposomes. The TE of DPPC first increased with the increasing concentration of PSO4, then decreased gradually. On the other hand, in the case of DOPC, the TE increased significantly upon addition of PSO4, then remained nearly constant. Though the exact dependence of TE on the PSO4 concentration differed in the two cases, its effect, in each case, was more than the effect of ß-sitosterol (POH). The ability of PSO4 for reducing the size and enhancing dispersibility and TE of liposomes can be useful for preparing cosmetics and pharmaceutical formulations.

Phase Behavior of the Bilayers Containing Hydrogenated Soy Lecithin and ß-Sitosteryl Sulfate.

The phase behaviors of systems containing saturated phosphatidylcholine (PC) and plant steroids can be important for designing new alternative delivery methods. In our previous studies, we found that even a small amount of ß-sitosteryl sulfate (PSO4) significantly affects the phase behavior, hydration properties, and liposomal properties of pure saturated phosphatidylcholines [Kafle, A.; Colloids Surf., B 2018, 161, 59-66; Kafle, A.; J. Oleo Sci. 2018, 67 (12), 1511-1519]. In the current paper, we are reporting the phase behavior of a more complex system consisting of hydrogenated soy lecithin (HLC), which is useful as a carrier in drug delivery systems or in cosmetics, and PSO4. HLC, which is composed of phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidic acid (PA), and lysophosphatidylcholine (LPC), demonstrated a versatile phase behavior. The PC component of HLC was found to separate from the PE and PA components as a result of nonideal mixing. At room temperature, these two domains represented two distinct gel phases denoted Lß1 and Lß2. The Lß1 phase selectively underwent transition into the liquid crystalline phase (Lα) at a lower temperature than Lß2. Upon addition of PSO4, at room temperature, the PC fraction gradually converted into the liquid-ordered (Lo) phase, while the (PE + PA) fraction remained unaffected. When heated above 60 °C, the whole material converted into the liquid crystalline phase. The observed fluidizing effect of PSO4 on HLC can find applications in preparing vehicles for moisture or drugs in cosmetic and pharmaceutical formulations.

Effects of ß-Sitosteryl Sulfate on the Properties of DPPC Liposomes.

The effect of ß-sitosteryl sulfate (PSO4) on the liposomal size, stability, fluidity, and dispersibility of DPPC liposomes prepared by vortex mixing, bath-sonication, and probe-sonication has been studied. PSO4 significantly decreases the particle size of the multilamellar liposomes (MLVs). The sizes of the vortexmixed and the bath-sonicated liposomes vary as a function of PSO4 concentration. On the other hand, PSO4 has only little effect on the particle sizes of probe sonicated liposomes. In some cases, the liposomal stability at higher PSO4 concentrations depends on the preparation method. PSO4 improves the dispersibility of the DPPC liposomes and enhances their hydration. It also increases the fluidity of the liposomes prepared by each method. Our results suggest that liposomes consisting of DPPC and PSO4 can be suitable as a cosmetic or pharmaceutical ingredient for the effective delivery of the active components into the body.

Effects of ß-Sitosteryl Sulfate on the Hydration Behavior of Dipalmitoylphosphatidylcholine.

We investigated the hydration behavior of dipalmitoylphosphatidylcholine (DPPC) bilayers containing sodium ß-sitosteryl sulfate (PSO4). PSO4 was found to enhance hydration in the headgroup region of DPPC bilayers. Therefore, with the incorporation of PSO4 into DPPC membranes, the amount of water required to reach the fully hydrated state was enhanced as indicated by the constant values of the main phase transition temperature (Tm) and the bilayer repeat distance (d). For example, with the addition of 20 mol% of PSO4, the saturation point was shifted to ~70 wt% water compared to ~40 wt% for pure DPPC and 47 wt% for DPPC-cholesterol. The effectiveness of PSO4 in fluidizing the membrane and enhancing its hydration state can be useful in the pharmaceutical and cosmetic industries.

Effects of ß-Sitosteryl Sulfate on the Phase Behavior and Hydration Properties of Distearoylphosphatidylcholine: a Comparison with Dipalmitoylphosphatidylcholine.

We have studied the phase behavior of distearoylphosphatidylcholine (DSPC) in the presence of sodium ß-sitosteryl sulfate (PSO4). PSO4 was found to induce sterol-rich and sterol-poor domains in the DSPC membrane. These two domains constitute a fluid, liquid ordered (Lo) phase and a gel (Lß) phase. PSO4 was less miscible in DSPC than in a dipalmitoylphosphatidylcholine (DPPC) membrane, as evidenced by its tendency to separate from the bilayer at a concentration of 50 mol%. This lack of miscibility was attributed to the greater van der Waals forces between the PC hydrocarbon chains. In addition to affecting the phase behavior, PSO4 also enhanced the hydration of the membrane. Despite its weaker interaction with DSPC compared to DPPC, its tendency to fluidize this phospholipid and enhance its hydration can be useful in formulating cosmetics and pharmaceutical products.

Characterization of the micelle structure of oleic acid-based gemini surfactants: effect of stereochemistry.

In this study, we synthesize a novel oleic acid-based gemini surfactant with carboxylate headgroups, and study the effect of stereochemistry (anti- vs. syn-) on self-aggregation properties in water. We investigate these properties using phase diagrams, static surface tension, and one-dimensional and two-dimensional nuclear magnetic resonance (NMR) measurements. We find that a phase transition from a hexagonal liquid crystal (H1) phase to a lamellar liquid crystal (Lα) phase occurs at a lower surfactant concentration in the syn form, when compared with the anti form. In addition, the syn form gemini surfactant forms micelles with a close packing of the headgroups via hydrogen bonding. This was supported by static surface tensiometry; the area occupied by surfactant molecules at the air/aqueous solution interface is smaller for the syn form than for the anti form. We propose that, for the syn form gemini surfactant, the closer packing of the headgroups as well as the hydrogen bonding network around the micelle interface prevent water penetration into the hydrophobic part of the micelle.

Effects of sodium ß-sitosteryl sulfate on the phase behavior of dipalmitoylphosphatidylcholine.

We have studied the phase behavior of dipalmitoylphosphatidylcholine (DPPC) containing sodium ß-sitosteryl sulfate (PSO4). PSO4 was found to lower the phase transition temperature of DPPC to a higher degree than cholesterol or ß-sitosterol. It also gave rise to the formation of a modulated (ripple) phase (Pß) at low to moderate concentrations. At concentrations greater than 25 mol%, it completely changed the membrane into a fluid phase. This shows that PSO4 is capable of disordering the hydrocarbon chains of PC efficiently. The characteristics of PSO4 for fluidizing the membrane can be useful for the pharmaceutical and cosmetics industries.

Physicochemical Evaluation of Micellar Solution and Lyotropic Phases Formed by Self-Assembled Aggregates of Morpholinium Geminis.

The micellar solution and the lyotropic liquid crystalline phases formed by gemini surfactants containing morpholinium headgroups are investigated for their self-aggregation and physicochemical properties in water. These gemini surfactants demonstrated good surface activity because they are able to undergo micellization at lower concentration and form nanosized micellar aggregates in dilute aqueous solution. The binary mixture of the morpholinium gemini surfactant-water system is investigated over a wide range of concentrations. The micellar solution of the morpholinium gemini surfactants demonstrated Newtonian fluidlike behavior between 10 and 50 wt % as the observed viscosities were independent of the applied shear rate. At higher concentration, morpholinium geminis formed self-assembled lyotropic phases in water. These liquid crystalline phases were characterized by small-angle X-ray scattering and polarized optical microscopy techniques.

Structural diversity, physicochemical properties and application of imidazolium surfactants: Recent advances.

The current review covers recent advances on development and investigation of cationic surfactants containing imidazolium headgroup, which are being extensively investigated for their self-aggregation properties and are currently being utilized in various conventional and non-conventional application areas. These surfactants are being used as: soft template for synthesis of mesoporous/microporous materials, drug and gene delivery agent, stabilizing agent for nanoparticles, dispersants for single/multi walled carbon nanotubes, antimicrobial and antifungal agent, viscosity modifiers, preparing nanocomposite materials, stabilizing microemulsions, corrosion inhibitors and catalyst for organic reactions. Recently several structural derivatives of these surfactants have been developed having many interesting physicochemical properties and they have demonstrated enormous potential in the area of nanotechnology, material science and biomedical science.

New ester based gemini surfactants: the effect of different cationic headgroups on micellization properties and viscosity of aqueous micellar solution.

A new series of ester functionalized cationic gemini surfactants having different cationic headgroups (i.e. piperidinium, pyrrolidinium, morpholinium and quaternary ammonium) have been synthesized and characterized using NMR and Mass spectroscopy. These new gemini surfactants were investigated for their micellization and viscosity properties using surface tension, conductivity, fluorescence and rheology thechniques. The physicochemical properties of the aqueous surfactant system were influenced by polarity, size and the nature of cationic headgroups as the surface, thermodynamic and viscosity properties of these gemini surfactants were found to be dependent on the type of cationic headgroup. The current research finding establishes the structure-property relationship of the surfactant molecule specifically taking into account the dominant role displayed by the nature of the cationic headgroup.

Bio-inspired surfactants capable of generating plant volatiles.

Plants are able to synthesize, store and release lipophilic organic molecules known as plant volatiles (PVs) utilizing specific biological pathways and different enzymes which play vital roles in the plant's defence and in dealing with biotic and abiotic stress situations. The process of generation, storage and release of PVs by plants acquired during the course of evolution is a very complex phenomenon. Bio-inspired molecular design of farnesol-based surfactants facilitates similar production, storage and release of PVs. The designed molecules adsorb at air-water interface and self-aggregate into micelles in aqueous system. The structural design of the molecules allows them to self-activate in water via intramolecular cation-π interactions. The activated molecules undergo molecular rearrangements generating volatile organic molecules both at interface and inside the micelle core. The molecules adsorbed at the interface initially release the formed volatile molecules creating vacant space at interface, thus thermodynamically directing the micelle to release the manufactured volatile products.

Self-aggregation and liquid crystalline behavior of new ester-functionalized quinuclidinolium surfactants.

A new type of ester-based cationic surfactant having a quinuclidinolium headgroup has been synthesized starting from linear fatty alcohols and has been characterized using spectroscopic techniques. The self-aggregation and thermodynamic properties of these surfactants have been investigated by pendant-drop surface tensiometry and conductivity measurements. The liquid crystalline behaviors of these surfactants were investigated by small-angle X-ray scattering (SAXS) technique. The quinuclidinolium headgroup demonstrated a unique ability to interlock among themselves thus affecting the physicochemical properties of surfactants in aqueous solution. The current research finding supports the new concept of headgroup interlocking which is supported by 1D and 2D NMR studies.

Gemini imidazolium surfactants: synthesis and their biophysiochemical study.

New gemini imidazolium surfactants 9-13 have been synthesized by a regioselective epoxy ring-opening reaction under solvent-free conditions. The surface properties of these new gemini surfactants were evaluated by surface tension and conductivity measurements. These surfactants have been found to have low critical micelle concentration (cmc) values as compared to other categories of gemini cationic surfactants and also showed the tendency to form premicellar aggregates in solution at sufficiently low concentration below their cmc values. The thermal degradation of these surfactants was determined by thermograviometry analysis (TGA). These new cationic surfactants have a good DNA binding capability as determined by agarose gel electrophoresis and ethidium bromide exclusion experiments. They have also been found to have low cytotoxicity by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay on the C6 glioma cell line.

Physicochemical studies of pyridinium gemini surfactants with promethazine hydrochloride in aqueous solution.

The mixed micellization and interfacial behavior of pyridinium gemini surfactants, 1,1'-(1,1'-(ethane-1,2-diylbis-(sulfanediyl))bis(alkane-2,1-diyl))dipyridinium bromide, i.e., [12-(S-2-S)-12], [14-(S-2-S)-14], [16-(S-2-S)-16] with a phenothiazine tranquilizer drug, promethazine hydrochloride (PMT), has been investigated by conductivity, surface tension and steady state fluorescence measurements. Different spectroscopic techniques like fluorescence, UV-visible and NMR were also employed to understand the nature of interactions between the pyridinium gemini surfactants and PMT. The various micellar, interfacial and associated thermodynamic parameters for different mole fractions of PMT-pyridinium gemini surfactant mixtures have been evaluated. Synergism was observed in the mixed micelle as well as the monolayer formed by these mixtures. The fluorescence quenching experiment indicates that the interactions between PMT and surfactants are hydrophobic in nature. The UV-visible measurements reveal the distinct formation of a drug-surfactant complex. The detailed mechanism for the type of interactions was further studied by NMR titrations which show cation-π interactions between PMT and pyridinium gemini surfactant molecules.

Synthesis and properties of thioether spacer containing gemini imidazolium surfactants.

Twelve new gemini imidazolium surfactants have been synthesized, having dodecyl, tetradecyl, hexadecyl, and octadecyl chain lengths and three different spacers (i.e., -S-(CH(2))(n)-S-), where n = 2, 3, and 4 and their surface properties have been evaluated by surface tension and conductivity methods. The thermal degradation of these new gemini surfactants was determined by thermogravimetric analysis (TGA). These surfactants have low cmc values as compared to other categories of gemini cationic surfactants and exhibit peculiarities at sufficiently low concentration because they were able to form premicellar aggregates over a wide range of concentration below their cmc values. The DNA binding affinity of these gemini surfactants determined by agarose gel electrophoresis and ethidium bromide exclusion experiments established their strong interaction with DNA, thereby protecting it against enzymatic degradation.

Synthesis, characterization and comparative evaluation of phenoxy ring containing long chain gemini imidazolium and pyridinium amphiphiles.

Two series of phenoxy ring containing long chain imidazolium and pyridinium based gemini amphiphiles have been synthesized from renewable cardanol oil having different spacers (i. e. -S-(CH(2))(n)-S-, where n is 2, 3, 4 & 6). Critical micelle concentration (cmc) of these new gemini amphiphiles has been determined by conductivity method. Further, these new cationic amphiphiles have been evaluated for their DNA binding capability by agarose gel electrophoresis, ethidium bromide exclusion experiments and transmission electron microscopy (TEM). The cytotoxicity of these new amphiphiles have been evaluated by MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. Comparative studies of these phenoxy ring containing long chain gemini imidazolium amphiphiles and their pyridinium analogues depicted low cmc values of the later but greater DNA interaction capability and low cytotoxicity of the former series of amphiphiles.

Novel gemini pyridinium surfactants: synthesis and study of their surface activity, DNA binding, and cytotoxicity.

New pyridinium gemini amphiphiles having ethane-1,2-dithiol spacer have been synthesized by regioselective electrophilic cobromination of alpha-olefins. Ethane-1,2-dithiol (1) and N-bromosuccinimide (6) on reaction with alpha-olefins (dodecene (2), tetradecene (3), hexadecene (4), and octadecene (5)) gave the respective 1,2-bis(2-bromoalkylthio)ethane (7-10). The bromoalkylthio ethers when reacted with pyridine (11) gave the respective gemini bispyridinium bromide (12-15). The surface properties of new geminis were evaluated by surface tension and conductivity measurements. These gemini surfactants have also been found to be having low cytotoxicity by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay on C6 glioma cells. The DNA binding capabilities of these amphiphiles have been determined below as well as above critical micelle concentration. The preliminary studies by agarose gel electrophoresis indicated chain length dependent DNA binding abilities which has further been proved by ethidium bromide exclusion experiments and transmission electron microscopy (TEM).