Exploring pH-Triggered Lamellar to Cubic Phase Transition in 2-Hydroxyoleic Acid/Monoolein Nanodispersions: Insights into Membrane Physicochemical Properties.

Self-assembled lipid nanoparticles (LNPs) are essential nanocarriers for drug delivery. Functionalization of LNPs with ionizable lipids creates pH-responsive nanoparticles that change structures under varying pH conditions, enabling pH-triggered drug release. Typically, bicontinuous cubic phase nanoparticles (Cubosomes) and lamellar structured vesicles (Liposomes) differ in lipid packing statuses, affecting drug release and cellular uptake. However, most research predominantly focuses on elucidating lattice structure changes of these LNPs without a deep investigation of lipid-membrane properties. Addressing this gap, our study delves into the lipid-membrane physicochemical property variations during the lamellar-to-cubic phase transition. Here, we prepared pH-responsive LNPs using 2-hydroxyoleic acid/monoolein (2-OHOA/MO) binary components. Small-angle X-ray scattering (SAXS) revealed a phase transition from lamellar vesicles (Lα) to cubosomes (Im3m/Pn3m) with pH reduction. Laurdan and 1,6-diphenyl-1,3,5-hexatriene (DPH) fluorescence probes tracked the lipid-water interfacial polarity and lipid-membrane fluidity variations during the phase transition. Raman spectroscopy provided further insights into lipid-membrane lipid chain packing and chain torsion. We observed that the changes in lipid-membrane properties coincided with the lamellar-to-cubic phase transition, emphasizing the interplay between the phase structure and lipid-membrane behaviors in the 2-OHOA/MO system. This study provides insights into the lipid-membrane properties variation during the pH-triggered phase transition in the 2-OHOA/MO system, guiding future research toward more effective and reliable pH-responsive drug delivery platforms.

Preparation and characterization of macrophage membrane camouflaged cubosomes as a stabilized and immune evasive biomimetic nano-DDS.

This study aims to develop a biomimetic nano-drug delivery system (nano-DDS) by employing a macrophage cell membrane camouflaging strategy to modify lyotropic liquid crystal nanoparticles (LLC-NPs). The cubic-structured LLC-NPs (Cubosomes, CBs) were prepared via a top-down approach (ultra-sonification) using monoolein (MO) and doped with the cationic lipid, DOTAP. The cell membrane camouflaging procedure induced changes in the cubic lipid phase from primitive cubic phase (QIIP) to a coexistence of QIIP and diamond cubic phase (QIID). The macrophage membrane camouflaging strategy protected CB cores from the destabilization by blood plasma and enhanced the stability of CBs. The in vitro experiment results revealed that the macrophage cell membrane coating significantly reduced macrophage uptake efficacy within 8 h of incubation compared to the non-camouflaged CBs, while it had minimal impact on cancer cell uptake efficacy. The macrophage membrane coated CBs showed lower accumulation in the heart, kidney and lungs in vivo. This study demonstrated the feasibility of employing cell membrane camouflaging on CBs and confirmed that the bio-functionalities of the CBs-based biomimetic nano-DDS were retained from the membrane source cells, and opened up promising possibilities for developing an efficient and safe drug delivery system based on the biomimetic approach.

Influence of cholesterol on hydrogen-bond dynamics of water molecules in lipid-bilayer systems at varying temperatures.

Cholesterol (Chol) plays a crucial role in shaping the intricate physicochemical attributes of biomembranes, exerting a considerable influence on water molecules proximal to the membrane interface. In this study, we conducted molecular dynamics simulations on the bilayers of two lipid species, dipalmitoylphosphatidylcholine (DPPC) and palmitoyl sphingomyelin; they are distinct with respect to the structures of the hydrogen-bond (H-bond) acceptors. Our investigation focuses on the dynamic properties and H-bonds of water molecules in the lipid-membrane systems, with a particular emphasis on the influence of Chol at varying temperatures. Notably, in the gel phase at 303 K, the presence of Chol extends the lifetimes of H-bonds of the oxygen atoms acting as H-bond acceptors within DPPC with water molecules by a factor of 1.5-2.5. In the liquid-crystalline phase at 323 K, on the other hand, H-bonding dynamics with lipid membranes remain largely unaffected by Chol. This observed shift in H-bonding states serves as a crucial key to unraveling the subtle control mechanisms governing water dynamics in lipid-membrane systems.

A methodology of quantifying membrane permeability based on returning probability theory and molecular dynamics simulation.

We propose a theoretical approach to estimate the permeability coefficients of substrates (permeants) for crossing membranes from donor (D) phase to acceptor (A) phase by means of molecular dynamics (MD) simulation. A fundamental aspect of our approach involves reformulating the returning probability (RP) theory, a rigorous bimolecular reaction theory, to describe permeation phenomena. This reformulation relies on the parallelism between permeation and bimolecular reaction processes. In the present method, the permeability coefficient is represented in terms of the thermodynamic and kinetic quantities for the reactive (R) phase that exists within the inner region of a membrane. One can evaluate these quantities using multiple MD trajectories starting from phase R. We apply the RP theory to the permeation of ethanol and methylamine at different concentrations (infinitely dilute and 1 mol % conditions of permeants). Under the 1 mol% condition, the present method yields a larger permeability coefficient for ethanol (0.12 ± 0.01 cm s-1) than for methylamine (0.069 ± 0.006 cm s-1), while the values of the permeability coefficient are satisfactorily close to those obtained from the brute-force MD simulations (0.18 ± 0.03 and 0.052 ± 0.005 cm s-1 for ethanol and methylamine, respectively). Moreover, upon analyzing the thermodynamic and kinetic contributions to the permeability, we clarify that a higher concentration dependency of permeability for ethanol, as compared to methylamine, arises from the sensitive nature of ethanol's free-energy barrier within the inner region of the membrane against ethanol concentration.

Investigating the impact of 2-OHOA-embedded liposomes on biophysical properties of cancer cell membranes via Laurdan two-photon microscopy imaging.

2-Hydroxyoleic acid (2-OHOA) has gained attention as a membrane lipid therapy (MLT) anti-cancer drug. However, in the viewpoint of anti-cancer drug, 2-OHOA shows poor water solubility and its effectiveness still has space for improvement. Thus, this study aimed to overcome the problems by formulating 2-OHOA into liposome dosage form. Furthermore, in the context of MLT reagents, the influence of 2-OHOA on the biophysical properties of the cytoplasmic membrane remains largely unexplored. To bridge this gap, our study specifically focused the alterations in cancer cell membrane fluidity and lipid packing characteristics before and after treatment. By using a two-photon microscope and the Laurdan fluorescence probe, we noted that liposomes incorporating 2-OHOA induced a more significant reduction in cancer cell membrane fluidity, accompanied by a heightened rate of cellular apoptosis when compared to the non-formulated 2-OHOA. Importantly, the enhanced efficacy of 2-OHOA within the liposomal formulation demonstrated a correlation with its endocytic uptake mechanism. In conclusion, our findings underscore the significant influence of 2-OHOA on the biophysical properties of cancer plasma membranes, emphasizing the potential of liposomes as an optimized delivery system for 2-OHOA in anti-cancer therapy.

Significance of in situ quantitative membrane property-morphology relation (QmPMR) analysis.

Deformation of the cell membrane is well understood from the viewpoint of protein interactions and free energy balance. However, the various dynamic properties of the membrane, such as lipid packing and hydrophobicity, and their relationship with cell membrane deformation are unknown. Therefore, the deformation of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and oleic acid (OA) giant unilamellar vesicles (GUVs) was induced by heating and cooling cycles, and time-lapse analysis was conducted based on the membrane hydrophobicity and physical parameters of "single-parent" and "daughter" vesicles. Fluorescence ratiometric analysis by simultaneous dual-wavelength detection revealed the variation of different hydrophilic GUVs and enabled inferences of the "daughter" vesicle composition and the "parent" membrane's local composition during deformation; the "daughter" vesicle composition of OA was lower than that of the "parents", and lateral movement of OA was the primary contributor to the formation of the "daughter" vesicles. Thus, our findings and the newly developed methodology, named in situ quantitative membrane property-morphology relation (QmPMR) analysis, would provide new insights into cell deformation and accelerate research on both deformation and its related events, such as budding and birthing.

Solvation dynamics on the diffusion timescale elucidated using energy-represented dynamics theory.

Photoexcitation of a solute alters the solute-solvent interaction, resulting in the nonequilibrium relaxation of the solvation structure, often called a dynamic Stokes shift or solvation dynamics. Thanks to the local nature of the solute-solvent interaction, the characteristics of the local solvent environment dissolving the solute can be captured by the observation of this process. Recently, we derived the energy-represented Smoluchowski-Vlasov (ERSV) equation, a diffusion equation for molecular liquids, which can be used to analyze the solvation dynamics on the diffusion timescale. This equation expresses the time development for the solvent distribution on the solute-solvent pair interaction energy (energy coordinate). Since the energy coordinate can effectively treat the solvent flexibility in addition to the position and orientation, the ERSV equation can be utilized in various solvent systems. Here, we apply the ERSV equation to the solvation dynamics of 6-propionyl-2-dimethylamino naphthalene (Prodan) in water and different alcohol solvents (methanol, ethanol, and 1-propanol) for clarifying the differences of the relaxation processes among these solvents. Prodan is a solvent-sensitive fluorescent probe and is thus widely utilized for investigating heterogeneous environments. On the long timescale, the ERSV equation satisfactorily reproduces the relaxation time correlation functions obtained from the molecular dynamics (MD) simulations for these solvents. We reveal that the relaxation time coefficient on the diffusion timescale linearly correlates with the inverse of the translational diffusion coefficients for the alcohol solvents because of the Prodan-solvent energy distributions among the alcohols. In the case of water, the time coefficient deviates from the linear relationship for the alcohols due to the difference in the extent of importance of the collective motion between the water and alcohol solvents.

Exploring the Influence of Morphology on Bipolaron-Polaron Ratios and Conductivity in Polypyrrole in the Presence of Surfactants.

This research aims to deepen the understanding of the relationship between conductivity and morphology in polypyrrole (PPy) via a comparison of the bipolaron to polaron ratios with a focus on the C-H deformation area. PPy samples were synthesized with different surfactants: sodium dodecyl sulfate (SDS), cetyltrimethylammonium bromide (CTAB), and tween 80 (TW). This study revealed that SDS significantly altered the bipolaron and polaron in the C-H deformation region and showed higher conductivity than other surfactants. Notably, the morphological shifts to a sheet-like structure when using ammonium sulfate (APS) contrasted with the particle-like form observed with ferric chloride (FeCl3). These results showed that if the oxidant changed, the bipolaron and polaron ratios in C-H deformation were unrelated to PPy morphology. However, this work showed a consistent relationship between SDS use, the bipolaron and polaron ratios in the C-H deformation, and the conductivity properties. Moreover, the natural positive charge of PPy and negatively charged SDS molecules may lead to an electrostatic interaction between PPy and SDS. This work assumes that this interaction might cause the transformation of polaron to bipolaron in the C-H deformation region, resulting in improved conductivity of PPy. This work offers more support for the future investigation of PPy characteristics.

Preparation and Characterization of Biodegradable Sponge-like Cryogel Particles of Chitosan via the Inverse Leidenfrost (iLF) Effect.

Chitosan-based cryogel particles were synthesized using the inverse Leidenfrost (iLF) effect, with glutaraldehyde employed as the cross-linker. The resulting cryogels exhibited a sponge-like morphology with micrometer-sized interconnected pores and demonstrated resilience, withstanding up to three compression-release cycles. These characteristics highlight the potential of chitosan cryogels for diverse applications, including adsorption and biomedical uses. We further investigated the influence of varying acetic acid concentrations on the properties of the chitosan cryogels. Our findings revealed that the particle size distribution of the cryogels ranged from 1300 to 2900 µm. As the concentration of acetic acid increased, the swelling degree of the chitosan cryogels decreased, stabilizing at an approximate value of around 6 at 0.03 mol of acetic acid. Additionally, the shift in the absorption peak of the OH and free amino groups from 3261 to 3404 cm-1 confirmed the cross-linking reaction between chitosan and glutaraldehyde.

Multiplicity of solvent environments in lipid bilayer revealed by DAS deconvolution of twin probes: Comparative method of Laurdan and Prodan.

Laurdan and Prodan were designed for the evaluation of the surrounding hydration state. When inserted into lipid bilayer systems, both probes are located at different positions and their fluorescence properties are drastically varied, depending on their surrounding environment. In this study, a novel method using the above fluorescence probes was proposed on the basis of fluorescence lifetime (τ) and emission peak (λ), called as τ vs. λ plot, determined by global analysis of their multiple fluorescence decays and deconvolution of these decay-associated spectra. According to the evaluation of τ vs. λ plot, the existence of multiple fluorescence components in the membrane was revealed. In addition, their fluorescence distribution properties, described on τ vs. λ plot, of each probe tended to correspond to the phase state and vertical direction of the lipid membrane. To assess the contribution of environmental effect to each distribution, we defined the region in the τ vs. λ plot, which was modeled from a series of solvent mixtures (hexane, acetone, ethanol and water) to emulate the complex environment in the 1,2-dipalmitoyl-sn-glycero-3-phosphocholine bilayer system. The distributions of fluorescence components of Laurdan and Prodan in lipid membranes were classified into each solvent species, and Prodan partition into bulk water was distinguished. The sensitivity of Prodan to the phase pretransition of the 1,2-dipalmitoyl-sn-glycero-3-phosphocholine bilayer system was also observed in increasing the temperature. Noticeably, most of the fluorescence components was assigned to the solvent model, except for a single component that has longer lifetime and shorter emission wavelength. This component was dominant in solid-ordered phase; hence, it is assumed to be a specific component in lipid membranes that cannot be represented by solvents. Although these are still qualitative analytical methods, the unique approach proposed in this study provides novel insights into the multi-focal property of the membrane.

Niosomes in cancer treatment: A focus on curcumin encapsulation.

Curcumin is widely used as a therapeutic drug for cancer treatment. However, its limited absorption and rapid excretion are the major therapeutic limitations to its clinical use. Using niosomes as a curcumin delivery system is a cheap, easy, and less toxic strategy for enhancing the absorption of curcumin by cells and delaying its excretion. Thus, there is a vital need to explore curcumin niosomes to configure the curcumin to suitably serve and aid current pharmacokinetics in treatments for cancer. To date, no comprehensive review has focused on the cytotoxic effects of curcumin niosomes on malignant cells. Thus, this review provides a critical analysis of the curcumin niosomes in cancer treatment, formulations of curcumin niosomes, characterizations of curcumin niosomes, and factors influencing their performance. The findings from this review article can strongly accelerate the understanding of curcumin niosomes and pave a brighter direction towards advances in the pharmaceutical, biotechnology, and medical industries.

Cholesterol as a Subsidiary Component of Sorbitan Surfactant-Based Aggregates: A Study of Formation, Hydrophobicity, and Estimation of Localization of Embedded Molecules.

Aggregates of amphiphilic molecules can be used as drug carriers, for which the properties can be modified by mixing with other molecules such as cholesterol. It is important to understand the effects of such additives on the properties because they directly define the material functions. In this work, we investigated the effect of cholesterol on the formation and hydrophobicity of aggregates of sorbitan surfactants. As cholesterol changed its formation from micelles to vesicles, an increase in hydrophobicity was seen, particularly in the middle regions compared with the shallow and deep regions. We show that this gradual hydrophobicity is related to the localization of the embedded molecules. 4-Hydroxy-TEMPO and 4-carboxy-TEMPO were preferentially localized in the shallow region of the aggregates, whereas 4-PhCO2-TEMPO was preferentially localized in the deep region of the vesicle. The localization of molecules depends on their chemical structure. However, the localization of 4-PhCO2-TEMPO in micelles was not observed, despite the similar hydrophobicity in the hydrophobic region within the aggregates. The localization of embedded molecules was related to other properties, such as molecular mobility.

Versatility of the Preparation Method for Macroporous Cryogel Particles Utilizing the Inverse Leidenfrost Effect.

We have investigated the versatility of a two-step preparation method, without a detergent, that combines both the inverse Leidenfrost effect and the cryogelation technique by using the macroporous particles of different kinds of monomers (four vinyl monomers) or a natural polymer (agarose). First, the precursor of polymers was dropped into liquid nitrogen to prepare the spherical frozen droplet by the inverse Leidenfrost effect. Second, the frozen droplets were cryo-polymerized at the frozen temperature; then, cryogel particles were prepared after thawing. Subsequently, the basic characteristics of the macroporous polymer particles obtained above were compared, focusing on the appearances, porous morphologies, and mechanical properties. It was found that the similar polymer particles could be obtained by the two-step preparation method, while there was a slight difference in their characteristics, depending on the type of monomers. Especially for the mechanical properties, the cryogel particles of the hydrophilic polymer exhibited a shape memory function with sponge-like elasticity, whereas the hydrophobic polymer particles were observed to be cracked after compression (i.e., no shape memory function). This work provides a versatile method of adopting various kinds of monomers and natural polymers for the preparation of macroporous particles. Hence, the method possibly has a potential to prepare and design "tailor-made" macroporous polymer particles for the application purpose.

Study of Chemical Polymerization of Polypyrrole with SDS Soft Template: Physical, Chemical, and Electrical Properties.

Polypyrrole (PPy) is a conductive polymer known for its biocompatibility and ease of synthesis. Chemically polymerized PPy was synthesized in the presence of sodium dodecyl sulfate (SDS), showing correlations among chemical properties, physical morphology, and electrical properties. Focused synthesis parameters included the pyrrole (Py) concentration, SDS concentration, and ammonium persulfate (APS)/Py ratio. The addition of SDS during chemical polymerization influenced the physical morphology of PPy by altering the self-assembling process via micelle formation, yielding sheet-like morphologies. However, the phenomenon also relied heavily on other synthesis parameters. Varying SDS concentrations within the 0.01 to 0.30 M window produced PPy sheets with no significant difference in optical band gap or physical size. While using 0.10 M SDS, an increase in Py concentration from 0.10 to 0.30 M yielded a larger size of PPy as the morphology changed from sheet-like to irregular shape. The band gap dropped from 2.35 to 1.10 eV, and the conductivity rose from 6.80 × 10-1 to 9.40 × 10-1 S/m. With an increase in the APS/Py ratio, the PPy product changed from a random to a sheet-like form. The product provided a larger average size, a decreased band gap, and increased electrical conductivity. Py polymerization in the absence of SDS revealed no significant change in shape or size as the Py concentration increased from 0.10 to 0.30 M; only a sphere-like form was observed, with a large band gap and small conductivity. Results from Raman spectral analysis indicated a correlation between optical band gap, physical morphology, and bipolaron/polaron ratio, mainly at the wavelengths associated with C-C stretching and C-H deformation. The increase in average size was associated with a decrease in band gap and resistance as well as an increase in the bipolaron/polaron ratio. This work indicates a strong correlation between size, morphology, electrical properties, and the bipolaron/polaron ratio of PPy in the presence of SDS.

Revealed Properties of Various Self-Assemblies in Two Catanionic Surfactant Systems in Relation to Their Polarity and Molecular Packing State.

A catanionic surfactant system is an aqueous solution or dispersion of cationic and anionic surfactants that spontaneously self-assemble into structures such as micelles, vesicles, and coacervates. Their structural diversity varies depending on the ratios of cationic and anionic surfactants (compositions), the chemical structure of the constituent molecules, etc. Herein, two types of catanionic surfactant systems were systematically characterized: (i) cetyltrimethylammonium bromide (CTAB) and sodium dodecyl sulfate (SDS), both typical ionic surfactants; and (ii) dodecylmethylimidazolium ammonium bromide ([C12mim]Br) and SDS, where the former is an ionic liquid. By observing the sample appearance, turbidity, and particle size, the phase state of each system was analyzed according to the total concentration of surfactants and the molar ratio of cationic surfactants to the total concentration. Especially, for specific compositions of catanionic surfactant vesicles (cataniosome), the closed structure of the vesicles was confirmed through calcein entrapment and release detected with a fluorescence assay. The polarities of the interface of the prepared self-assemblies were evaluated using a fluorescence probe, Laurdan. The packing state of the molecules in the formed self-assembly structure was estimated using Raman spectroscopy. The results clearly indicate consistent phase-transition behavior for the CTAB-SDS (i) and [C12mim]Br-SDS (ii) systems, depending on the total surfactant concentration and composition, while the membrane properties of the two systems differed. The cataniosome formed in the CTAB-SDS system was in a tightly packed membrane state and more hydrophobic than that formed in the [C12mim]Br-SDS system owing to the difference in the structure of the constituting molecule: [C12mim]Br has a larger head group and shorter acyl chain than CTAB. The self-assembly properties evaluated in this study were compared with those of typical lipid membranes, liposomes (lipid vesicles), to determine a possible application of the catanionic systems with various self-assembly formulations.

Characterization of Phase Separated Planar Lipid Bilayer Membrane by Fluorescence Ratio Imaging and Scanning Probe Microscope.

The lipid membrane forms nanodomains (rafts) and shows heterogeneous properties. These nanodomains relate to significant roles in various cell functions, and thus the analysis of the nanodomains in phase-separated lipid membranes is important to clarify the function and role of the nanodomains. However, the lipid membrane possesses small-sized nanodomains and shows a small height difference between the nanodomains and their surroundings at certain lipid compositions. In addition, nanodomain analysis sometimes requires highly sensitive and expensive apparatus, such as a two-photon microscope. These have prevented the analysis by the conventional fluorescence microscope and by the topography of the scanning probe microscope (SPM), even though these are promising methods in macroscale and microscale analysis, respectively. Therefore, this study aimed to overcome these problems in nanodomain analysis. We successfully demonstrated that solvatochromic dye, LipiORDER, could analyze the phase state of the lipid membrane at the macroscale with low magnification lenses. Furthermore, we could prove that the phase mode of SPM was effective in the visualization of specific nanodomains by properties difference as well as topographic images of SPM. Hence, this combination method successfully gave much information on the phase state at the micro/macro scale, and thus this would be applied to the analysis of heterogeneous lipid membranes.

Characterization of entrapment behavior of polyphenols in nanostructured lipid carriers and its effect on their antioxidative activity.

Polyphenols are widely used as antioxidant agents to protect human health. Resveratrol, kaempferol, and quercetin have been reported to have potent antioxidant activity; however, these compounds have many problems related to their practical application, such as instability and insolubility. Thus, a nanostructured lipid carrier (NLC) was utilized as a drug delivery system (DDS) to overcome these limitations. This study investigated the particle stability, drug loading performance, and antioxidant activity of polyphenols-incorporated NLCs. The particle size and distribution were suitable for DDS applications, and all the samples demonstrated good stability after 2 months of storage. Based on Raman spectroscopy analysis, polyphenols were successfully encapsulated in NLCs. Quantitative high-performance liquid chromatography analysis indicated that NLCs could load resveratrol more than kaempferol and quercetin. In addition, NLCs have successfully improved all the antioxidant activity per unit concentration of polyphenol (specific antioxidant activity) compared to the free polyphenols. Quercetin-incorporated NLCs showed the highest specific antioxidant activity. This result is the opposite of entrapment efficiency and actual antioxidant activity, most likely influenced by the location of entrapped polyphenol molecules. As it was performed, NLCs are highly recommended to be applied as an antioxidant delivery system.

Preferential adsorption of L-tryptophan by L-phospholipid coated porous polymer particles.

Chiral selective adsorption of L-amino acid, tryptophan (Trp) was achieved using phospholipid membrane-coated porous polymer particles (PPPs). PPPs with numerous pores were prepared by in situ polymerization of divinylbenzene, and then coated with 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC, L-phospholipid) via the impregnation method. Elemental mapping of energy dispersive X-ray (EDX) analysis revealed that DPPC molecules were distributed to the surface and the inner part of PPPs, where almost all the DPPC molecules applied for impregnation were deposited on PPPs. The phospholipid membrane properties of DPPC-PPPs were characterized using the fluorescence probe 6-lauroyl-2-dimethylaminonaphthalene (Laurdan). The results show that DPPC-PPPs possessed a lipid membrane-like environment similar to pure DPPC liposomes, especially at temperatures below 35 °C. DPPC-PPPs slightly adsorbed L-Trp and D-Trp at 45 °C, while DPPC-PPPs significantly adsorbed L-Trp but not D-Trp at 30 °C: enantio excess (e.e.) was 75.0%. The time course of Trp adsorption was investigated: for both enantiomers, similar adsorption behaviors were observed for 30 h, thus suggesting surface adsorption onto DPPC-PPPs. L-Trp adsorption continued after 30 h, suggesting that L-Trp could be distributed in the inner part of DPPC-PPPs. Interestingly, the reused DPPC-PPPs featured improved adsorption performance, suggesting that the deposited DPPC membranes on PPPs could act as chiral selectors for L-Trp. The optical resolution of L-/D-Trp was performed using DPPC-PPPs, resulting in the e.e. of D-Trp was > 60%. Thus, DPPC-PPPs have the potential of chiral selective adsorption of L-amino acid, which can be used as chiral separation materials.

A Simple Method for Continuous Synthesis of Bicelles in Microfluidic Systems.

Bicelle has great potential for drug delivery systems due to its small size and biocompatibility. The conventional method of bicelle preparation contains a long process and harsh conditions, which limit its feasibility and damage the biological substances. For these reasons, a continuous manufacturing method in mild conditions has been demanded. Here, we propose a novel method for DMPC/DHPC bicelle synthesis based on a microfluidic device without heating and freezing processes. Bicelles were successfully prepared using this continuous method, which was identified by the physicochemical properties and morphologies of the synthesized assemblies. Experimental and analytical studies confirm that there is critical lipid concentration and critical mixing time for bicelle synthesis in this microfluidic system. Furthermore, a linear relation between the actual composition of bicelle and initial lipid ratio is deduced, and this enables the size of bicelles to be controlled.

Insight into the Exosomal Membrane: From Viewpoints of Membrane Fluidity and Polarity.

Numerous research studies have been done for exosomes, particularly focusing on membrane proteins and included nucleic acids, and the volume of the knowledge about the lipids in the exosomal membrane has been increasing. However, the dynamic property of the exosomal membrane is hardly studied. By employing milk exosome as an example, herein the exosomal membrane was characterized focusing on the membrane fluidity and polarity. The lipid composition and phase state of milk exosome (exosome from bovine milk) were estimated. The milk exosome contained enriched Chol (43.6 mol % in total lipid extracts), which made the membrane in the liquid-ordered (lo) phase by interacting with phospholipids. To suggest a model of exosomal vesicle cargo, the liposome compositions that mimic milk exosome were studied: liposomes were made of cholesterol (Chol), milk sphingomyelin (milk SM), and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC). By using fluorescent probes 1,6-diphenyl-1,3,5-hexatriene and 6-dodecanoyl-2-dimethylaminonaphthalene, the microenvironments of submicron-sized membranes of exosome and model liposomes were investigated. The membrane fluidity of milk exosome was slightly higher than those of Chol/milk SM/POPC liposomes with a similar content of Chol, suggesting the presence of enriched unsaturated lipids. The most purposeful membrane property was obtained by the liposome composition of Chol/milk SM/POPC = 40/15/45. From the above, it is concluded that Chol is a fundamental component of the milk exosomal membrane to construct the enriched lo phase, which could increase the membrane rigidity and contribute to the function of exosome.