A Solvent-Templated Porous Liquid Crystal Elastomer with Tactile Sensation beyond Reversible Actuation toward Versatile Artificial Muscles.

Liquid crystal elastomers (LCEs), as a classical two-way shape-memory material, are good candidates for developing artificial muscles that mimic the contraction, expansion, or rotational behavior of natural muscles. However, biomimicry is currently focused more on the actuation functions of natural muscles dominated by muscle fibers, whereas the tactile sensing functions that are dominated by neuronal receptors and synapses have not been well captured. Very few studies have reported the sensing concept for LCEs, but the signals were still donated by macroscopic actuation, that is, variations in angle or length. Herein, we develop a conductive porous LCE (CPLCE) using a solvent (dimethyl sulfoxide (DMSO))-templated photo-cross-linking strategy, followed by carbon nanotube (CNT) incorporation. The CPLCE has excellent reversible contraction/elongation behavior in a manner similar to the actuation functions of skeletal muscles. Moreover, the CPLCE shows excellent pressure-sensing performance by providing real-time electrical signals and is capable of microtouch sensing, which is very similar to natural tactile sensing. Furthermore, macroscopic actuation and tactile sensation can be integrated into a single system. Proof-of-concept studies reveal that the CPLCE-based artificial muscle is sensitive to external touch while maintaining its excellent actuation performance. The CPLCE with tactile sensation beyond reversible actuation is expected to benefit the development of versatile artificial muscles and intelligent robots.

Pluronic P123/DMSO Lyotropic Liquid Crystal for Incorporating Bioactive Substances for Topical Application.

Lyotropic liquid crystals (LLCs) have attracted considerably growing interest in drug delivery applications over the last years. The structure of LLC matrices is complementary to cell membranes and provides an efficient, controlled, and selective release of drugs. In this work, a complex of experimental methods was used to characterize binary LLCs Pluronic P123/DMSO and triple LLC systems Pluronic P123/DMSO/Ibuprofen, which are interesting as transdermal drug delivery systems. Liquid crystalline, thermal, and rheological properties of LLCs were studied. Concentration and temperature areas of the lyomesophase existence were found, and phase transition enthalpies were evaluated. Intermolecular interactions among the components were studied by infrared (IR) spectroscopy. In vitro studies of Ibuprofen (Ibu) release from various LLCs allow differentiation of its release depending on the polymer content. Atomic force microscopy and contact angle methods were used to characterize the surface morphology of the hydrophobic membrane, which was used as a stratum corneum model, and also evaluate the adhesion work of the LLCs. A complex analysis of the results provided by these experimental methods allowed revealing correlations between the phase behavior and rheological characteristics of the LLCs and release kinetics of ibuprofen. The proposed biocompatible systems have considerable potential for a transdermal delivery of bioactive substances.

Characteristic structures of liquid crystal monomers in EI-MS analysis and the potential application in suspect screening.

Liquid crystal monomers (LCMs) are of emerging concern due to their ubiquitous presence in indoor and outdoor environments and their potential negative impacts on human health and ecosystems. Suspect screening approaches have been developed to monitor thousands of LCMs that could enter the environment, but an updated suspect list of LCMs is difficult to maintain given the rapid development of material innovations. To facilitate suspect screening for LCMs, in-silico mass fragmentation model and quantitative structure-activity relationship (QSPR) models were applied to predict electron ionization (EI) mass spectra of LCMs. The in-silico model showed limited predictive power for EI mass spectra, while the QSPR models trained with 437 published mass spectra of LCMs achieved an acceptable absolute error of 12 percentage points in predicting the relative intensity of the molecular ion, but failed to predict the mass-to-charge ratio of the base peak. A total of 41 characteristic structures were identified from an updated suspect list of 1606 LCMs. Multi-phenyl groups form the rigid cores of 85% of LCMs and produce 154 characteristic peaks in EI mass spectra. Monitoring the characteristic structures and fragments of LCMs may help identify new LCMs with the same rigid cores as those in the suspect list.

Clinical application of hempseed or flaxseed oil-based lyotropic liquid crystals: Evaluation of their impact on skin barrier function.

The principal function of skin is to form an effective barrier between the human body and its environment. Impaired barrier function represents a precondition for the development of skin diseases such as atopic dermatitis (AD), which is the most common inflammatory skin disease characterized by skin barrier dysfunction. AD significantly affects patients' quality of life, thus, there is a growing interest in the development of novel delivery systems that would improve therapeutic outcomes. Herein, eight novel lyotropic liquid crystals (LCCs) were investigated for the first time in a double-blind, interventional, before-after, single-group trial with healthy adult subjects and a twice-daily application regimen. LCCs consisted of constituents with skin regenerative properties and exhibited lamellar micro-structure, especially suitable for dermal application. The short- and long-term effects of LCCs on TEWL, SC hydration, erythema index, melanin index, and tolerability were determined and compared with baseline. LCCs with the highest oil content and lecithin/Tween 80 mixture stood out by providing a remarkable 2-fold reduction in TEWL values and showing the most distinctive decrease in skin erythema levels in both the short- and long-term exposure. Therefore, they exhibit great potential for clinical use as novel delivery systems for AD treatment, capable of repairing skin barrier function.

Synchronized Codelivery of Combination Chemotherapies Intratumorally Using a Lipidic Lyotropic Liquid Crystal System.

In this work, an injectable in situ depot-forming lipidic lyotropic liquid crystal (L3C) system is developed to codeliver a precisely synchronized combination of chemotherapeutics intratumorally. The developed L3C system is composed of amphiphilic lipids and surfactants, including monoolein, phosphatidylcholine, tocopherol acetate, and d-α-tocopherol polyethylene glycol 1000 succinate. Owing to its amphiphilic nature, the developed formulation can coaccommodate both hydrophobic and hydrophilic chemotherapeutic moieties simultaneously. The study presents a proof of concept by designing a combination chemotherapy regimen in vitro and demonstrating its in vivo translation using doxorubicin and paclitaxel as model hydrophilic and hydrophobic drug moieties, respectively. The synchronized combination of the two chemotherapeutics with maximum synergistic activity was identified, coloaded in the developed L3C system at predefined stoichiometric ratios, and evaluated for antitumor efficacy in the 4T1 breast tumor model in BALB/c mice. The drug-loaded L3C formulation is a low-viscosity injectable fluid with a lamellar phase that transforms into a hexagonal mesophase depot system upon intratumoral injection. The drug-loaded depot system locally provides sustained intratumoral delivery of the chemotherapeutics combination at their precisely synchronized ratio for over a period of one month. Results demonstrate that the exposure of the tumor to the precisely synchronized intratumoral chemotherapeutics combination via the developed L3C system resulted in significantly higher antitumor activity and reduced cardiotoxicity compared to the unsynchronized combination chemotherapy or the synchronized but uncoordinated drug delivery administered by a conventional intravenous route. These findings demonstrate the potential of the developed L3C system for achieving synchronized codelivery of the chemotherapeutics combination intratumorally and improving the efficacy of combination chemotherapy.

Molecular Orientation Behavior of Lyotropic Liquid Crystal-Carbon Dot Hybrids in Microfluidic Confinement.

Lyotropic liquid crystals represent an important class of anisotropic colloid systems. Their integration with optically active nanoparticles can provide us with responsive luminescent media that offer new fundamental and applied solutions for biomedicine. This paper analyzes the molecular-level behavior of such composites represented by tetraethylene glycol monododecyl ether and nanoscale carbon dots in microfluidic channels. Microfluidic confinement allows for simultaneously applying multiple factors, such as flow dynamics, wall effects, and temperature, for the precise control of the molecular arrangement in such composites and their resulting optical properties. The microfluidic behavior of composites was characterized by a set of analytical and modeling tools such as polarized and fluorescent microscopy, dynamic light scattering, and fluorescent spectroscopy, as well as image processing in Matlab. The composites were shown to form tunable anisotropic intermolecular structures in microchannels with several levels of molecular ordering. A predominant lamellar structure of the composites was found to undergo additional ordering with respect to the microchannel axis and walls. Such an alignment was controlled by applying shear and temperature factors to the microfluidic environment. The revealed molecular behavior of the composite may contribute to the synthesis of hybrid organized media capable of polarized luminescence for on-chip diagnostics and biomimetics.

Antibacterial and anti-biofilm activities of antibiotic-free phosphatidylglycerol/docosahexaenoic acid lamellar and non-lamellar liquid crystalline nanoparticles.

Infectious diseases, particularly those associated with biofilms, are challenging to treat due to an increased tolerance to commonly used antibiotics. This underscores the urgent need for innovative antimicrobial strategies. Here, we present an alternative simple-by-design approach focusing on the development of biocompatible and antibiotic-free nanocarriers from docosahexaenoic acid (DHA) that has the potential to combat microbial infections and phosphatidylglycerol (DOPG), which is attractive for use as a biocompatible prominent amphiphilic component of Gram-positive bacterial cell membranes. We assessed the anti-bacterial and anti-biofilm activities of these nanoformulations (hexosomes and vesicles) against S. aureus and S. epidermidis, which are the most common causes of infections on catheters and medical devices by different methods (including resazurin assay, time-kill assay, and confocal laser scanning microscopy on an in vitro catheter biofilm model). In a DHA-concentration-dependent manner, these nano-self-assemblies demonstrated strong anti-bacterial and anti-biofilm activities, particularly against S. aureus. A five-fold reduction of the planktonic and a four-fold reduction of biofilm populations of S. aureus were observed after treatment with hexosomes. The nanoparticles had a bacteriostatic effect against S. epidermidis planktonic cells but no anti-biofilm activity was detected. We discuss the findings in terms of nanoparticle-bacterial cell interactions, plausible alterations in the phospholipid membrane composition, and potential penetration of DHA into these membranes, leading to changes in their structural and biophysical properties. The implications for the future development of biocompatible nanocarriers for the delivery of DHA alone or in combination with other anti-bacterial agents are discussed, as novel treatment strategies of Gram-positive infections, including biofilm-associated infections.

Structural, Optical, and Mechanical Insights into Cellulose Nanocrystal Chiral Nematic Film Engineering by Two Assembly Techniques.

Iridescent cellulose nanocrystal (CNC) films with chiral nematic nanostructures exhibit great potential in optical devices, sensors, painting, and anticounterfeiting applications. CNCs can assemble into a chiral nematic liquid crystal structure by evaporation-assisted self-assembly (EISA) and vacuum-assisted self-assembly (VASA) techniques. However, there is a lack of comprehensive examinations of their structure-property correlations, which are essential for fabricating materials with unique properties. In this work, we gained insights into the optical, mechanical, and structural differences of CNC films engineered using the two techniques. In contrast to the random self-assembly at the liquid-air interface in EISA, the continuous external pressure in the VASA process forces CNCs to assemble at the filter-liquid interface. This results in fewer defects in the interfaces between tactoids and highly ordered cholesteric phases. Owing to the distinct CNC assembly behaviors, the films prepared by these two methods show great differences in the nanostructure, microstructure, and macroscopic morphology. Consequently, the highly ordered cholesteric structure gives VASA-CNC films a more uniform structural color and enhanced mechanical performance. These fundamental understandings of the relationship of structure-property nanoengineering through various assembly techniques are essential for designing and constructing high-performance chiral iridescent CNC materials.

The Influence of PVP Polymer Topology on the Liquid Crystalline Order of Itraconazole in Binary Systems.

This study presents a novel approach by utilizing poly(vinylpyrrolidone)s (PVPs) with various topologies as potential matrices for the liquid crystalline (LC) active pharmaceutical ingredient itraconazole (ITZ). We examined amorphous solid dispersions (ASDs) composed of ITZ and (i) self-synthesized linear PVP, (ii) self-synthesized star-shaped PVP, and (iii) commercial linear PVP K30. Differential scanning calorimetry, X-ray diffraction, and broad-band dielectric spectroscopy were employed to get a comprehensive insight into the thermal and structural properties, as well as global and local molecular dynamics of ITZ-PVP systems. The primary objective was to assess the influence of PVPs' topology and the composition of ASD on the LC ordering, changes in the temperature of transitions between mesophases, the rate of their restoration, and finally the solubility of ITZ in the prepared ASDs. Our research clearly showed that regardless of the PVP type, both LC transitions, from smectic (Sm) to nematic (N) and from N to isotropic (I) phases, are effectively suppressed. Moreover, a significant difference in the miscibility of different PVPs with the investigated API was found. This phenomenon also affected the solubility of API, which was the greatest, up to 100 µg/mL in the case of starPVP 85:15 w/w mixture in comparison to neat crystalline API (5 µg/mL). Obtained data emphasize the crucial role of the polymer's topology in designing new pharmaceutical formulations.

Liquid crystal monomers disrupt photoreceptor patterning of zebrafish larvae via thyroid hormone signaling.

Liquid crystal monomers (LCMs) are the raw material for liquid crystal displays, and their use is steadily increasing in electronic products. Recently, LCMs have been reported to be novel endocrine disrupting chemicals, however, the mechanisms underlying their potential for thyroid hormone disruption and visual toxicity are not well understood. In this study, six widely used fluorinated LCMs (FLCMs) were selected to determine putative mechanisms underlying FLCM-induced toxicity to the zebrafish thyroid and visual systems. Exposure to FLCMs caused damage to retinal structures and reduced cell density of ganglion cell layer, inner nuclear layer, and photoreceptor layer approximately 12.6-46.1%. Exposure to FLCMs also disrupted thyroid hormone levels and perturbed the hypothalamic-pituitary-thyroid axis by affecting key enzymes and protein in zebrafish larvae. A thyroid hormone-dependent GH3 cell viability assay supported the hypothesis that FLCMs act as thyroid hormone disrupting chemicals. It was also determined that FLCMs containing aliphatic ring structures may have a higher potential for T3 antagonism compared to FLCMs without an aliphatic ring. Molecular docking in silico suggested that FLCMs may affect biological functions of thyroxine binding globulin, membrane receptor integrin, and thyroid receptor beta. Lastly, the visual motor response of zebrafish in red- and green-light was significantly inhibited following exposure to FLCMs. Taken together, we demonstrate that FLCMs can act as thyroid hormone disruptors to induce visual dysfunction in zebrafish via several molecular mechanisms.

A Wearable Thin-Film Hydrogel Laser for Functional Sensing on Skin.

Flexible photonics offers the possibility of realizing wearable sensors by bridging the advantages of flexible materials and photonic sensing elements. Recently, optical resonators have emerged as a tool to improve their oversensitivity by integrating with flexible photonic sensors. However, direct monitoring of multiple psychological information on human skin remains challenging due to the subtle biological signals and complex tissue interface. To tackle the current challenges, here, we developed a functional thin film laser formed by encapsulating liquid crystal droplet lasers in a flexible hydrogel for monitoring metabolites in human sweat (lactate, glucose, and urea). The three-dimensional cross-linked hydrophilic polymer serves as the adhesive layer to allow small molecules to penetrate from human tissue to generate strong light--matter interactions on the interface of whispering gallery modes resonators. Both the hydrogel and cholesteric liquid crystal microdroplets were modified specifically to achieve high sensitivity and selectivity. As a proof of concept, wavelength-multiplexed sensing and a prototype were demonstrated on human skin to detect human metabolites from perspiration. These results present a significant advance in the fabrication and potential guidance for wearable and functional microlasers in healthcare.

Rapid Surface Charge Mapping Based on a Liquid Crystal Microchip.

Rapid surface charge mapping of a solid surface remains a challenge. In this study, we present a novel microchip based on liquid crystals for assessing the surface charge distribution of a planar or soft surface. This chip enables rapid measurements of the local surface charge distribution of a charged surface. The chip consists of a micropillar array fabricated on a transparent indium tin oxide substrate, while the liquid crystal is used to fill in the gaps between the micropillar structures. When an object is placed on top of the chip, the local surface charge (or zeta potential) influences the orientation of the liquid crystal molecules, resulting in changes in the magnitude of transmitted light. By measuring the intensity of the transmitted light, the distribution of the surface charge can be accurately quantified. We calibrated the chip in a three-electrode configuration and demonstrated the validity of the chip for rapid surface charge mapping using a borosilicate glass slide. This chip offers noninvasive, rapid mapping of surface charges on charged surfaces, with no need for physical or chemical modifications, and has broad potential applications in biomedical research and advanced material design.

DNA liquid crystals with AIE effect toward humidity-indicating biomaterials.

In this study, by fabricating DNA doped with tetraphenylethene-containing ammonium surfactant, the resulting solvent-free DNA ionic complex could undergo a humidity-induced phase change that could be well tracked by the fluorescence signal of the surfactant. Taking advantage of the humidity-induced change in fluorescence, the reported ionic DNA complex could accurately indicate the humidity in real time.

High-resolution low-cost LCD 3D printing for microfluidics and organ-on-a-chip devices.

The fabrication of microfluidic devices has progressed from cleanroom manufacturing to replica molding in polymers, and more recently to direct manufacturing by subtractive (e.g., laser machining) and additive (e.g., 3D printing) techniques, notably digital light processing (DLP) photopolymerization. However, many methods require technical expertise and DLP 3D printers remain expensive at a cost ∼15-30 K USD with ∼8 M pixels that are 25-40 µm in size. Here, we introduce (i) the use of low-cost (∼150-600 USD) liquid crystal display (LCD) photopolymerization 3D printing with ∼8-58 M pixels that are 18-35 µm in size for direct microfluidic device fabrication, and (ii) a poly(ethylene glycol) diacrylate-based ink developed for LCD 3D printing (PLInk). We optimized PLInk for high resolution, fast 3D printing and biocompatibility while considering the illumination inhomogeneity and low power density of LCD 3D printers. We made lateral features as small as 75 µm, 22 µm-thick embedded membranes, and circular channels with a 110 µm radius. We 3D printed microfluidic devices previously manufactured by other methods, including an embedded 3D micromixer, a membrane microvalve, and an autonomous capillaric circuit (CC) deployed for interferon-γ detection with excellent performance (limit of detection: 12 pg mL-1, CV: 6.8%). We made PLInk-based organ-on-a-chip devices in 384-well plate format and produced 3420 individual devices within an 8 h print run. We used the devices to co-culture two spheroids separated by a vascular barrier over 5 days and observed endothelial sprouting, cellular reorganization, and migration. LCD 3D printing together with tailored inks pave the way for democratizing access to high-resolution manufacturing of ready-to-use microfluidic and organ-on-a-chip devices by anyone, anywhere.

Potential and performance of anisotropic 19F NMR for the enantiomeric analysis of fluorinated chiral active pharmaceutical ingredients.

Controlling the enantiomeric purity of chiral drugs is of paramount importance in pharmaceutical chemistry. Isotropic 1H NMR spectroscopy involving chiral agents is a widely used method for discriminating enantiomers and quantifying their relative proportions. However, the relatively weak spectral separation of enantiomers (1H Δδiso(R, S)) in frequency units at low and moderate magnetic fields, as well as the lack of versatility of a majority of those agents with respect to different chemical functions, may limit the general use of this approach. In this article, we investigate the analytical potential of 19F NMR in anisotropic chiral media for the enantiomeric analysis of fluorinated active pharmaceutical ingredients (API) via two residual anisotropic NMR interactions: the chemical shift anisotropy (19F-RCSA) and dipolar coupling ((19F-19F)-RDC). Lyotropic chiral liquid crystals (CLC) based on poly-γ-benzyl-L-glutamate (PBLG) show an interesting versatility and adaptability to enantiodiscrimination as illustrated for two chiral drugs, Flurbiprofen® (FLU) and Efavirenz® (EFA), which have very different chemical functions. The approach has been tested on a routine 300 MHz NMR spectrometer equipped with a standard probe (5 mm BBFO probe) in a high-throughput context (i.e., ≈10 s of NMR experiments) while the performance for enantiomeric excess (ee) measurement is evaluated in terms of trueness and precision. The limits of detection (LOD) determined were 0.17 and 0.16 µmol ml-1 for FLU and EFA, respectively, allow working in dilute conditions even with such a short experimental duration. The enantiodiscrimination capabilities are also discussed with respect to experimental features such as CLC composition and temperature.

A Molecular Rheology Dynamics Study on 3D Printing of Liquid Crystal Elastomers.

This work presents a rheological study of a biocompatible and biodegradable liquid crystal elastomer (LCE) ink for three dimensional (3D) printing. These materials have shown that their structural variations have an effect on morphology, mechanical properties, alignment, and their impact on cell response. Within the last decade LCEs are extensively studied as potential printing materials for soft robotics applications, due to the actuation properties that are produced when liquid crystal (LC) moieties are induced through external stimuli. This report utilizes experiments and coarse-grained molecular dynamics to study the macroscopic rheology of LCEs in nonlinear shear flow. Results from the shear flow simulations are in line with the outcomes of these experimental investigations. This work believes the insights from these results can be used to design and print new material with desirable properties necessary for targeted applications.

Microviscosity-Assisted Disaggregation of a Model Ophthalmic Drug and FRET-Controlled Singlet Oxygen Generation in Lyotropic Liquid Crystals.

Different phases of lyotropic liquid crystals (LLCs), made up of mesogen-like sodium dodecyl sulfate (SDS), mainly bestow different bulk viscosities. Along with this, the role of microviscosities of the individual LLC phases is of immense interest because a minute change in it due to guest incorporation can cause significant alteration in their property as a potential energy transfer scaffold. Recently, LLCs have been identified as plausible drug delivery agents for ocular treatments. In this direction, the present work illustrates photophysical modulations of an important laser dye as well as an ophthalmic medicine, coumarin 6 (C6), inside different LLC phases in an aqueous medium. C6 molecules spontaneously accumulate in water, leading to aggregation-caused quenching (ACQ) of fluorescence. However, the different phases of the LLCs prepared from SDS and water helped in disintegrating the C6 colonies to various extents depending upon the microviscosity. The heterogeneity in the LLC phases, in turn, could modulate the Förster resonance energy transfer (FRET) between C6 and the LLC incorporated with N-doped carbon nanoparticles (N-CNPs). The N-CNPs act as potential photosensitizers and generate singlet oxygen (1O2), a reactive oxygen species (ROS), to different extents. Microviscosities of the prepared LLCs were calculated by using fluorescence correlation spectroscopy (FCS). The different phases of the LLCs, viz., lamellar and hexagonal, with different microviscosities controlled the extent of C6 disaggregation and hence the FRET and the ROS generation. The results are encouraging since ROS generation has a significant role in the vision mechanism and PDT-based applications. LLC-based drug administration with potential FRET to control ROS generation may become handy in ophthalmology. The LLC phases used in this experiment not only served the purpose of drug delivery but also the photophysical events therein are compatible with the ocular environment.

Label-free, liquid crystal-based aptasensor for detecting carbendazim at picomolar levels.

We describe a simple and sensitive liquid-crystal (LC)-based method for quantifying carbendazim (CBZ) by exploiting aptamer-specific recognition at the aqueous-LC interface. The method relies on the interfacial interaction between an aptamer and cetyltrimethylammonium bromide (CTAB); this interaction varies depending on the amount of CBZ. In the absence of CBZ, the aptamer disrupts the CTAB monolayer through electrostatic attraction, leading to a transition from homeotropic to tilted ordering of the LCs. As CBZ concentrations rise, the formation of aptamer-CBZ complexes increases, preserving the vertical alignment of the LCs by reducing collapse of the CTAB layer caused by electrostatic interactions. Using these methods, we achieved a CBZ detection limit of 3.12 pM (0.000597 µg/L) over a linear range of 0.05-5 nM. Moreover, we quantified CBZ levels in peach, soil, and tap water samples. Our LC-based detection method has significant research potential, offering sensitive, and straightforward detection of CBZ.

A hybrid thermal-biological recycling route for efficient extraction of metals and metalloids from end-of-life liquid crystal displays (LCDs).

Waste liquid crystal displays (LCDs) are one of the most substantial and rapidly growing e-waste streams that contain a notable amount of critical, precious, and toxic elements. This study presented a novel thermal-biological hybrid method for resource recovery from waste LCDs. Through the design of a multistage thermal treatment process with the addition of optimized 20 wt% B2O3 to waste, the LCD's glass structure was separated into two interconnected phases, resulting in the transfer of metals from the LCD's glass phase to the B2O3 phase that can solubilize in the acid solution. Following the thermal treatment step, the biometabolites of Aspergillus niger were used for bioleaching of In, Sr, Al, and As from the obtained thermally treated product. The optimal bioleaching parameters were a pulp density of 10 g/L, temperature of 70 °C, and leaching time of 2 days, which led to the highest extraction of 82.6% Al, 70.8% As, 64.5% In, and 36.2% Sr from thermally treated LCD waste, representing a multifold increase in Al, As, and Sr extraction levels compared to untreated waste. This study demonstrated that the proposed hybrid method could successfully overcome waste complexities and ensure effective element extraction from discarded LCDs.

Non-lamellar lyotropic liquid crystalline nanoparticles as nanocarriers for enhanced drug encapsulation of atorvastatin calcium and proanthocyanidins.

Atorvastatin calcium (ATV) and proanthocyanidins (PAC) have a strong antioxidant activity, that can benefit to reduce the atherosclerotic plaque progression. Unfortunately, the bioavailability of ATV is greatly reduced due to its limited drug solubility while the PAC drug is unstable upon exposure to the atmospheric oxygen. Herein, the lyotropic liquid crystalline nanoparticles (LLCNPs) constructed by a binary mixture of soy phosphatidylcholine (SPC) and citric acid ester of monoglyceride (citrem) at different weight ratios were used to encapsulate the hydrophobic ATV and hydrophilic PAC. The LLCNPs were further characterized by small-angle X-ray scattering and dynamic light scattering. Depending on the lipid composition, the systems have a size range of 140-190 nm and were able to encapsulate both drugs in the range of 90-100%. Upon increasing the citrem content of drug-loaded LLCNPs, the hexosomes (H2) was completely transformed to an emulsified inverse micellar (L2). The optimum encapsulation efficiency (EE) of ATV and PAC were obtained in citrem/SPC weight ratio 4:1 (L2) and 1:1 (H2), respectively. There was a substantial change in the mean size and PDI of the nanoparticles upon 30 days of storage with the ATV-loaded LLCNPs exhibiting greater colloidal instability than PAC-loaded LLCNPs. The biphasic released pattern (burst released at the initial stage followed by the sustained released at the later stage) was perceived in ATV formulation, while the burst drug released pattern was observed in PAC formulations that could be attributed by its internal H2 structure. Interestingly, the cytokine studies showed that the PAC-LLCNPs promisingly up regulate the expressions of tumor necrosis factor-alpha (TNF-α) better than the drug-free and ATV-loaded LLCNPs samples. The structural tunability of citrem/SPC nanoparticles and their effect on physicochemical characteristic, biological activities and potential as an alternative drug delivery platform in the treatment of atherosclerosis are discussed.