Nanomedicines, while having been approved for cancer therapy, present many challenges such as low stability, rapid clearance, and nonspecificity leading to off-target toxicity. Cubosomes are porous lyotropic liquid crystalline nanoparticles that have shown great premise as drug delivery vehicles; however, their behavior in vivo is largely underexplored, hindering clinical translation. Here, we have engineered cubosomes based on the space group Im3m that are loaded with copper acetylacetonate as a model drug, and their surfaces are functionalized for the first time with Affimer proteins via copper-free click chemistry to actively target overexpressed carcinoembryonic antigens on LS174T colorectal cancer cells. Unlike nontargeted cubosomes, Affimer tagged cubosomes showed preferential accumulation in cancer cells compared to normal cells not only in vitro (2D monolayer cell culture and 3D spheroid models) but also in vivo in colorectal cancer mouse xenografts, while exhibiting low nonspecific absorption and toxicity in other vital organs. Cancerous spheroids had maximum cell death compared to noncancerous cells upon targeted delivery. Xenografts subjected to targeted drug-loaded cubosomes showed a 5-7-fold higher drug accumulation in the tumor tissue compared to the liver, kidneys, and other vital organs, a significant decrease in tumor growth, and an increased survival rate compared to the nontargeted group. This work encompasses the first thorough preclinical investigation of Affimer targeted cubosomes as a cancer therapeutic.
Non-small cell lung cancer (NSCLC) is one of the major causes of cancer-related mortality globally. Despite the availability of therapeutic options, the improvement in patient survival is yet to be achieved. Recent advances in natural product (e.g., Rutin) research, therapeutic nanotechnology and especially the combination of both could aid in achieving significant improvements in the treatment or management of NSCLC. In this study, we explore the anti-cancer activity of Rutin-loaded liquid crystalline nanoparticles (LCNs) in an in vitro model where we have employed the A549 human lung epithelial carcinoma cell line. The anti-proliferative activity was determined by MTT and Trypan blue assays, whereas, the anti-migratory activity was evaluated by the scratch wound healing assay and a modified Boyden chamber assay. We also evaluated the anti-apoptotic activity by Annexin V-FITC staining, and the colony formation activity was studied using crystal violet staining. Here, we report that Rutin-LCNs showed promising anti-proliferative and anti-migratory activities. Furthermore, Rutin-LCNs also induced apoptosis in the A549 cells and inhibited colony formation. The findings warrant further detailed and in-depth anti-cancer mechanistic studies of Rutin-LCNs with a focus towards a potential therapeutic option for NSCLC. LCNs may help to enhance the solubility of Rutin used in the treatment of lung cancer and hence enhance the anticancer effect of Rutin.
The lyotropic phase behavior of four common and easily accessible glycosides, n-octyl α-d-glycosides, namely, α-Glc-OC8, α-Man-OC8, α-Gal-OC8, and α-Xyl-OC8, was investigated. The presence of normal hexagonal (HI), bicontinuous cubic (VI), and lamellar (Lα) phases in α-Glc-OC8 and α-Man-OC8 including their phase diagrams in water reported previously was verified by deuterium nuclear magnetic resonance (2H NMR), via monitoring the D2O spectra. Additionally, the partial binary phase diagrams and the liquid crystal structures formed by α-Gal-OC8 and α-Xyl-OC8 in D2O were constructed and confirmed using small- and wide-angle X-ray scattering and 2H NMR. The average number of bound water molecules (nb) per headgroup in the Lα phase was determined by the systematic measurement of the quadrupolar splitting of D2O over a wide range of molar ratio values (glycoside/D2O), especially at high glucoside composition. The number of bound water molecules bound to the headgroup was found to be around 1.5-2.0 for glucoside, mannoside, and galactoside, all of which possesses four OH groups. In the case of xyloside, which has only three OH groups, the bound water content is ∼2.0. Our findings confirmed that the bound water content of all n-octyl α-d-glycosides studied is lower compared to the number of possible hydrogen bonding sites possibly due to the fact that most of the OH groups are involved in intralayer interaction that holds the lipid assembly together.
Aim: In the present study, the inhibitory potential of rutin-loaded liquid crystalline nanoparticles (LCNs) on oxidative stress was determined in human bronchial epithelial cells (BEAS-2B) by analysing the expression levels of different antioxidant (NADPH quinine oxidoreductase-1 (NQO1); γ-glutamyl cysteine synthetase catalytic subunit (GCLC)) and pro-oxidant (NADPH oxidase (Nox)-4; Nox2B) genes. Results: Our findings revealed that the rutin-loaded LCNs inhibited the genes, namely Nox2B and Nox4, which caused oxidative stress. In addition, these nanoparticles demonstrated an upregulation in the expression of the antioxidant genes Gclc and Nqo-1 in a dose-dependent manner. Conclusion: The study indicates the promising potential of rutin-loaded LCNs as an effective treatment strategy in patients with high oxidant loads in various respiratory diseases.
Intranasal administration is poised as a competent method in delivering drugs to the brain, because the nasal route has a direct link with the central nervous system bypassing the formidable blood-brain barrier. C17-monoglycerol ester (MGE) and glyceryl monooleate (GMO) as liquid crystal (LC)-forming lipids possess desirable formulation characteristics as drug carriers for intranasally administered drugs. This study investigated the effect of LC formulations on the pharmacokinetics of tranilast (TL), a lipophilic model drug, and its distribution in the therapeutic target regions of the brain in rats. The anatomical biodistribution of LC formulations was monitored using micro-computed tomography tandem in vivo imaging systems. MGE and GMO effectively formed LC with suitable particle size, zeta potential, and viscosity supporting the delivery of TL to the brain. MGE and GMO LC formulations enhanced brain uptake by 10- to 12-fold and 2- to 2.4- fold, respectively, compared with TL solution. The olfactory bulb had the highest TL concentration and fluorescent signals among all the brain regions, indicating a direct nose-to-brain delivery pathway of LC formulations. LC-forming lipids, MGE and GMO, are potential biomaterials in formulations intended for intranasal administration.
A series of liquid crystal molecules with two Schiff base linking units and a cinnamaldehyde core with different terminal groups were synthesized and characterized. The intermediates of 4-heptyloxybenzaldehyde (1a) and 4-dodeyloxybenzaldehyde (1b) were synthesized through the alkylation of 4-hydroxybenzaldehyde with a series of bromoalkane. A condensation reaction of cinnamaldehyde, 1,4-phenylenediamine and a series of substituted benzaldehydes with different terminal groups such as bromo, chloro, hydroxy, cinnamaldehyde, hydrogen, methoxy, heptyloxy and dodecyloxy produced a series of new cinnamaldehyde-based compounds, 2-9, respectively. All these compounds were characterized using Fourier transform infrared (FTIR) spectroscopy, nuclear magnetic resonance (NMR) spectroscopy, and CHN elemental analysis. The liquid crystal properties of these compounds were determined using polarized optical microscopy (POM), and their transitions were further confirmed using differential scanning calorimetry (DSC). Compounds with chloro, bromo, methoxy, heptyloxy, and dodecyloxy substituents are mesogenic compounds with nematic phase behavior. However, the other compounds were found to be non-mesogenic without any mesophase transitions. The structure-property relationship was investigated in order to study the effect of different terminal groups and Schiff base linking units on the liquid crystalline behavior of these compounds.
Two series of new hexasubstituted cyclotriphosphazene derivatives were successfully synthesized and characterized. These derivatives are differentiated by two types of linking units in the molecules such as amide-azo (6a-j) and azo-azo (8a-j). The homologues of the same series contain different terminal substituents such as heptyl, nonyl, decyl, dodecyl, tetradecyl, hydroxyl, carboxyl, chloro, nitro, and amino groups. All the intermediates and final compounds were characterized using Fourier transform infrared spectroscopy (FT-IR), nuclear magnetic resonance spectroscopy (NMR), and Carbon, Hydrogen, and Nitrogen (CHN) elemental analysis. Liquid crystal properties for all compounds were determined using polarized optical microscope (POM). It was found that only intermediates 2a-e with nitro and alkoxyl terminal chains showed a smectic A phase. All the final compounds with alkoxyl substituents are mesogenic with either smectic A or C phases. However, other intermediates and compounds were found to be non-mesogenic. The study on the fire retardancy of final compounds was determined using limiting oxygen index (LOI) method. The LOI value of pure polyester resin (22.53%) was increased up to 24.71% after treating with 1 wt% of hexachlorocyclotriphosphazene (HCCP). Moreover, all the compounds gave positive results on the LOI values and compound 6i with the nitro terminal substituent showed the highest LOI value of 27.54%.
A series of new hexasubstituted cyclotriphosphazene compounds (4a-j) consisting of two Schiff base linking units and different terminal substituents was successfully synthesized and characterized. The structures of these compounds were confirmed using Fourier Transform Infra-Red (FTIR), Nuclear Magnetic Resonance (NMR), and CHN elemental analysis. Polarized optical microscopy (POM) was used to determine their liquid-crystal behavior, which was then further confirmed using differential scanning calorimetry (DSC). Compounds 4a-i with heptyl, nonyl, decyl, dodecyl, tetradecyl, hydroxy, 4-carboxyphenyl, chloro, and nitro terminal ends, respectively, showed the liquid-crystal properties, whereas compound 4j with the amino group was found to be non-mesogenic. The attachment of an electron-donating group in 4j eventually give a non-mesogenic product. The study of the fire-retardant properties of these compounds was done using the limiting oxygen index (LOI). In this study, polyester resin (PE) was used as a matrix for moulding, and the LOI value of pure PE was 22.53%. The LOI value increased to 24.71% when PE was incorporated with 1 wt.% of hexachlorocyclotriphosphazene (HCCP), thus indicating that HCCP has a good fire-retardant properties. The result showed that all the compounds have good agreement in their LOI values. Compound 4i with a nitro terminal group gave the highest LOI value of 28.37%.
Battery Monitoring System (BMoS) is an electronic system that monitors rechargeable battery cells or packs with various parameters, such as battery voltage, current and State-of-Charge (SoC). This system can be used to avoid overcharging or over-discharging of batteries to increase its shelf life. However, BMoS on the market is very expensive and not suitable for low cost embedded systems. As the Arduino Uno is widely used for low cost microcontroller boards, easy programming environment, and open-source platforms for building electronic projects, therefore, this study focuses on Arduino Uno BMoS based system. This system consists of current and voltage sensors, an Arduino Uno microcontroller and a liquid crystal display (LCD). In order to develop this system, there are three objectives to be achieved. First, the relationship between input and output of the sensors must be derived mathematically. The mathematical expression obtained can be verified by connecting and disconnecting the circuit with load and monitoring the value of output sensors. Then, a complete prototype of the BMoS was developed by connecting the LCD, current and voltage sensors to the Arduino Uno microcontroller. The complete prototype was tested using an 11.1 V of Lithium-ion battery and a DC motor as a load. From the results, the current sensor shows zero value when no load is connected as no current flow. The LCD also displays 11.1V of battery voltage when fully charged. Using the developed system, the user can monitor the current, the voltage and the SoC of the battery to ensure the battery is not overcharged and overused. The development of the BMoS can help to monitor the operation and performance of the batteries in any electronic systems. At the end of this study, the complete BMoS prototype gives benefits to the user and makes work easier.
Lyotropic nonlamellar liquid crystalline nanoparticles (NPs) (LCN), such as cubosomes and hexosomes, are useful tools for applications in drug delivery because of their unique structural properties. LCNs are highly versatile carriers that can be applied for use with topical, oral, and intravenous treatments. In recent years, significant research has focused on improving their preparation and characterization, including controlling drug release and enhancing the efficacy of loaded bioactive molecules. Nevertheless, the clinical translation of LCN-based carriers has been slow. In this review, we highlight recent advances and challenges in the development and application of LCN, providing examples of their topical, oral, and intravenous drug delivery applications, and discussing translational obstacles to LCN as a NP technology.
With the advancement of the fourth industrial revolution, the demand for LCD has widely accelerated as monitoring screens for computers and cell phones. Consequently, old LCD panels are expected to end up as a tremendous amount of e-waste. Apart from transparent electrodes and transistor, waste LCD panel also contains hazardous liquid crystal compound that can contaminate the landfill site. Thus, removing the material from waste LCD was investigated. In this study, water at subcritical state was applied at temperatures between 100 and 360 °C. Initially, the liquid crystals were extracted using toluene and were used to compare with subcritical water. The specific compounds of the liquid crystals were not identified. The liquid crystals (12 mg/g-LCD) were entirely removed from the LCD panel when treated above 300 °C by means of extraction with the subcritical water. Although liquid crystal was successfully removed, recovery was complicated due to the degradation of liquid crystals above 250 °C. A recovery of 70% was obtained at 250 °C without deformation of the molecules. Consequently, this study has shown that although it is not practical to recover LC from LCD panel waste using subcritical water, liquid crystals can be removed efficiently. This method is auspicious in reducing hazardous liquid crystal from waste LCD panel before their disposals at landfill sites.
Also recognized as carbohydrate liquid crystals, glycolipids are amphiphiles whose basic unit comprises of a sugar group attached to an alkyl chain. Glycolipids are amphitropic, which means these materials form liquid crystal self-assemblies when dry (thermotropic) as well as when dissolved in solvents (lyotropic/surfactants) such as water. Many glycolipids are also naturally derived since these can be found in cell membranes. Their membrane and surfactant functions are largely understood through their lyotropic properties. While glycolipids are expected to play major roles as eco-friendly surfactants in the global surfactant market, their usefulness as thermotropic liquid crystal material is, to date, unknown, due to relatively lack of research performed and data reported in the literature. Understandably since glycolipids are hygroscopic with many hydroxy groups, removing the last trace water is very challenging. In recent time, with careful lyophilization and more consistent characterization technique, some researchers have attempted serious studies into "dry" or anhydrous glycolipids. Motivated by possible developments of novel thermotropic applications, some results from these studies also provide surprising new understanding to support conventional wisdom of the lyotropic systems. Here we review the dry state of glycosides, a family of glycolipids whose sugar headgroup is linked to the lipid chain via a glycosidic oxygen linker. The structure property relationship of both linear and anhydrous Guerbet glycosides will be examined. In particular, how the variation of sugar stereochemistry (e.g. anomer vs. epimer), the chain length and chain branching affect the formation of thermotropic liquid crystals phases, which not only located under equilibrium but also far from equilibrium conditions (glassy phase) are scrutinized. The dry glycolipid assembly has been subjected to electric and magnetic fields and the results show interesting behaviors including a possible transient current generation.
The demonstration of the structure-properties relationship of shape-dependent photocatalysts remains a challenge today. Herein, one-dimensional (1-D)-like titania (TiO2), as a model photocatalyst, has been synthesized under a strong magnetic field in the presence of a magnetically responsive liquid crystal as the structure-aligning agent to demonstrate the relationship between a well-aligned structure and its photocatalytic properties. The importance of the 1-D-like TiO2 and its relationship with the electronic structures that affect the electron-hole recombination and the photocatalytic activity need to be clarified. The synthesis of 1-D-like TiO2 with liquid crystal as the structure-aligning agent was carried out using the sol-gel method under a magnetic field (0.3 T). The mixture of liquid crystal, 4'-pentyl-4-biphenylcarbonitrile (5CB), tetra-n-butyl orthotitanate (TBOT), 2-propanol, and water, was subjected to slow hydrolysis under a magnetic field. The TiO2-5CB took a well-aligned whiskerlike shape when the reaction mixture was placed under the magnetic field, while irregularly shaped TiO2-5CB particles were formed when no magnetic field was applied. It shows that the strong interaction between 5CB and TBOT during the hydrolysis process under a magnetic field controls the shape of titania. The intensity of the emission peaks in the photoluminescence spectrum of 1-D-like TiO2-5CB was lowered compared with the TiO2-5CB synthesized without the magnetic field, suggesting the occurrence of electron transfer from 5CB to the 1-D-like TiO2-5CB during ultraviolet irradiation. Apart from that, direct current electrical conductivity and Hall effect studies showed that the 1-D-like TiO2 composite enhanced electron mobility. Thus, the recombination of electrons and holes was delayed due to the increase in electron mobility; hence, the photocatalytic activity of the 1-D-like TiO2 composite in the oxidation of styrene in the presence of aqueous hydrogen peroxide under UV irradiation was enhanced. This suggests that the 1-D-like shape of TiO2 composite plays an important role in its photocatalytic activity.
A new class of liquid crystalline acetylide-imine system was successfully synthesized, characterized
and deposited on indium tin oxide (ITO) coated substrate via electrochemical deposition
method for potential organic film application. The relationship between liquid crystal
molecular structure, phase transition temperature and electrical performance was evaluated.
The mesomorphic properties were identified via polarized optic microscopy (POM) which displayed
fan-shaped texture of smectic A phase and their corresponding transition enthalpies
are in concurrence with DSC and TGA studies. The findings from the conductivity analysis
revealed that the fabricated film exhibits good electrical performance where it displayed
linear current-voltage relationship of I-V curve. Therefore, this proposed type of molecular
framework has given an ideal indication to act as transporting material for application in
optoelectronic devices.
In this study, we developed positively charged liquid crystalline nanoparticles (LCN) coated with chitosan (CHI) to enhance the skin permeation and distribution of 5α-reductase inhibitors for the treatment of androgenetic alopecia. LCN and surface-modified LCN (CHI-LCN) were prepared by ultrasonication method, and their physicochemical properties were characterized. In vitro and in vivo skin permeation and retention were studied using porcine abdominal skin and mice skin using the Franz diffusion cell. Skin distribution and cellular uptake of LCN and CHI-LCN were also investigated. The particle size and surface charge were 244.9 ± 2.1 nm and -19.2 ± 1.1 mV, respectively, for LCNs and 300.0 ± 7.6 nm and 24.7 ± 2.4 mV, respectively, for CHI-LCN. The permeation of 5α-reductase inhibitors was significantly greater with CHI-LCN compared with LCN, whereas there was no significant difference observed in the skin distribution. In fluorescence studies, fluorescence intensity was higher for CHI-LCNs throughout the skin, whereas more intense fluorescence was seen only in the epidermis layer for LCN. CHI-LCN showed greater cellular uptake than LCN, resulting in internalization of 98.5 ± 1.9% of nanoparticles into human keratinocyte cells. In conclusion, surface modification of LCN with CHI is a promising strategy for increasing skin permeation of 5α-reductase inhibitors for topical delivery.
Non-lamellar liquid crystalline aqueous nanodispersions, known also as ISAsomes (internally self-assembled 'somes' or nanoparticles), are gaining increasing interest in drug solubilisation and bio-imaging, but they often exhibit poor hemocompatibility and induce cytotoxicity. This limits their applications in intravenous drug delivery and targeting. Using a binary mixture of citrem and soy phosphatidylcholine (SPC) at different weight ratios, we describe a library of colloidally stable aqueous and hemocompatible nanodispersions of diverse nanoarchitectures (internal self-assembled nanostructures). This engineered library is structurally stable in human plasma as well as being hemocompatible (non-hemolytic, and poor activator of the complement system). By varying citrem to lipid weight ratio, the nanodispersion susceptibility to macrophage uptake could also be modulated. Finally, the formation of nanodispersions comprising internally V2 (inverse bicontinuous cubic) and H2 (inverse hexagonal) nanoarchitectures was achieved without the use of an organic solvent, a secondary emulsifier, or high-energy input. The tunable binary citrem/SPC nanoplatform holds promise for future development of hemocompatible and immune-safe nanopharmaceuticals.
The molecular dynamics of a synthetic branched chain glycolipid, 2-decyl-tetradecyl-β-d-maltoside (C14-10G2), in the dry assemblage of smectic and columnar liquid crystal phases has been studied by dielectric spectroscopy as a function of frequency and temperature during the cooling process. Strong relaxation modes were observed corresponding to the tilted smectic and columnar phases, respectively. At low frequency (∼900 Hz to 1 kHz) in the smectic phase, Process I* was observed due to the tilted sugar bilayer structure. The process continued in the columnar phase (Process I) with an abrupt dynamic change due to phase transition in the frequency range of ∼1.3 kHz to 22 kHz. An additional process (Process II) was observed in the columnar phase with a broader relaxation in the frequency range of ∼10 Hz to 1 kHz. A bias field dependence study was performed in the columnar phase and we found that the relaxation strength rapidly decreased with increased applied dc bias field. This relaxation originates from a collective motion of polar groups within the columns. The results of dielectric spectroscopy were supported by a molecular dynamics simulation study to identify the origin of the relaxation processes, which could be related to the chirality and hydrogen bonds of the sugar lipid.
Two new ether substituted azodyes were synthesized and characterized by different spectral analysis such as (1)H NMR, (13)C NMR, FTIR and UV/Vis. Synthesized compounds were used to study the photoisomerization phenomenon by using UV-Vis spectro-photometer. Interesting polarity dependent effect is observed for the first time on these materials. Trans-cis (E-Z) and cis-trans (Z-E) conversion occurred within 41 s and 445 min, respectively for both the compounds in solutions. Polarizing optical microscopy studies revealed that there is no liquid crystal phase for both the compounds. The dramatic variation in the optical property is speculated to be the polarity of the chemical species. These derivatives are useful to fabricate optical data storage devices.
Cell migration is a key contributor to wound repair. This study presents findings indicating that the liquid crystal based cell traction force transducer (LCTFT) system can be used in conjunction with a bespoke cell traction force mapping (CTFM) software to monitor cell/surface traction forces from quiescent state in real time. In this study, time-lapse photo microscopy allowed cell induced deformations in liquid crystal coated substrates to be monitored and analyzed. The results indicated that the system could be used to monitor the generation of cell/surface forces in an initially quiescent cell, as it migrated over the culture substrate, via multiple points of contact between the cell and the surface. Future application of this system is the real-time assaying of the pharmacological effects of cytokines on the mechanics of cell migration.