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.

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.

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.

Synthesis and Mesomorphic Properties of Liquid Crystals with 5-(4-Alkoxyphenylethynyl)tropolone.

New troponoid liquid crystals with 5-(4-alkoxyphenylethynyl)tropolone cores were synthesized. The 5-(4-alkoxyphenylethynyl)tropolones were obtained by the palladium-catalyzed cross-coupling of 5-iodotropolone with 4-alkoxyphenylacetylenes. The 2-alkoxy-5-(4-alkoxyphenylethynyl)tropones (1A) showed enantiotropic smectic phases, such as smectic A, C, and B. The 2-(4-alkoxy)benzoyloxy-5-(4-alkoxyphenylethynyl)tropones (1B) had enantiotropic nematic and smectic C phases. The 2-alkoxytropone derivatives (1A) had higher clearing temperatures and lower melting points than the corresponding benzene derivatives (2A). However, the 2-(4-alkoxybenzoyl)tropone derivatives (1B) had lower clearing temperatures and higher melting points than the corresponding benzene derivatives (2B).

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.

Self-Assembly of Unusually Stable Thermotropic Network Phases by Cellobiose-Based Guerbet Glycolipids.

Bicontinuous thermotropic liquid crystal (LC) materials, e.g., double gyroid (DG) phases, have garnered significant attention due to the potential utility of their 3D network structures in wide-ranging applications. However, the utility of these materials is significantly constrained by the lack of robust molecular design rules for shape-filling amphiphiles that spontaneously adopt the saddle curvatures required to access these useful supramolecular assemblies. Toward this aim, we synthesized anomerically pure Guerbet-type glycolipids bearing cellobiose head groups and branched alkyl tails and studied their thermotropic LC self-assembly. Using a combination of differential scanning calorimetry, polarized optical microscopy, and small-angle X-ray scattering, our studies demonstrate that Guerbet cellobiosides exhibit a strong propensity to self-assemble into DG morphologies over wide thermotropic phase windows. The stabilities of these assemblies sensitively depend on the branched alkyl tail structure and the anomeric configuration of the glycolipid in a previously unrecognized manner. Complementary molecular simulations furnish detailed insights into the observed self-assembly characteristics, thus unveiling molecular motifs that foster network phase self-assembly that will enable future designs and applications of network LC materials.

Hydrodynamics and multiscale order in confluent epithelia.

We formulate a hydrodynamic theory of confluent epithelia: i.e. monolayers of epithelial cells adhering to each other without gaps. Taking advantage of recent progresses toward establishing a general hydrodynamic theory of p-atic liquid crystals, we demonstrate that collectively migrating epithelia feature both nematic (i.e. p = 2) and hexatic (i.e. p = 6) orders, with the former being dominant at large and the latter at small length scales. Such a remarkable multiscale liquid crystal order leaves a distinct signature in the system's structure factor, which exhibits two different power-law scaling regimes, reflecting both the hexagonal geometry of small cells clusters and the uniaxial structure of the global cellular flow. We support these analytical predictions with two different cell-resolved models of epithelia - i.e. the self-propelled Voronoi model and the multiphase field model - and highlight how momentum dissipation and noise influence the range of fluctuations at small length scales, thereby affecting the degree of cooperativity between cells. Our construction provides a theoretical framework to conceptualize the recent observation of multiscale order in layers of Madin-Darby canine kidney cells and pave the way for further theoretical developments.

Regulating the structural polymorphism and protein corona composition of phytantriol-based lipid nanoparticles using choline ionic liquids.

Lipid-based lyotropic liquid crystalline nanoparticles (LCNPs) face stability challenges in biological fluids during clinical translation. Ionic Liquids (ILs) have emerged as effective solvent additives for tuning the structure of LCNP's and enhancing their stability. We investigated the effect of a library of 21 choline-based biocompatible ILs with 9 amino acid anions as well as 10 other organic/inorganic anions during the preparation of phytantriol (PHY)-based LCNPs, followed by incubation in human serum and serum proteins. Small angle X-ray scattering (SAXS) results show that the phase behaviour of the LCNPs depends on the IL concentration and anion structure. Incubation with human serum led to a phase transition from the inverse bicontinuous cubic (Q2) to the inverse hexagonal (H2) mesophase, influenced by the specific IL present. Liquid chromatography-mass spectrometry (LC-MS) and proteomics analysis of selected samples, including PHY control and those with choline glutamate, choline hexanoate, and choline geranate, identified abundant proteins in the protein corona, including albumin, apolipoproteins, and serotransferrin. The composition of the protein corona varied among samples, shedding light on the intricate interplay between ILs, internal structure and surface chemistry of LCNPs, and biological fluids.

Detection of glyphosate residues in agricultural products using liquid-crystal-based sensor exploiting competitive binding of glyphosate and Cu2+ at the aqueous/LC interface and capillary tube test strip.

Glyphosate is a widely used herbicide that poses both health and environmental risks. In this study, we propose a liquid crystal (LC)-based assay for glyphosate detection that exploits the unique properties of LC materials. The nematic LC 4-cyano-4'-pentylbiphenyl (5CB) was employed as the sensing material and a self-assembled monolayer of octadecyltrichlorosilane (OTS) was used to modify glass substrates. The assay involved strong competition for coordination with Cu2+ for glyphosate, resulting in changes in the LC texture. By monitoring and analyzing the optical images of the LC film using polarizing microscopy, we detected and quantified the glyphosate concentrations. The proposed assay demonstrated high sensitivity and selectivity toward glyphosate in the detection range of 1-300 nM with a limit of detection of 0.26 nM. Moreover, the assay successfully applied to analyze glyphosate in spiked samples, including tap water, soil, and cabbage, and satisfactory recovery rates were achieved. Based on this detection principle, capillary tube test strips were developed for on-site applications. The detection thresholds of the test strips were controlled by varying the Cu2+ concentration. The developed LC-based assay is a rapid and reliable glyphosate detection method with potential applications in environmental monitoring and food safety.

Patterning of Protein-Sequestered Liquid-Crystal Droplets Using Acoustic Wave Trapping.

Development of spatially organized structures and understanding their role in controlling kinetics of multistep chemical reactions are essential for the successful design of efficient systems and devices. While studies that showcase different types of methodologies for the spatial organization of various colloidal systems are known, design and development of well-defined hierarchical assemblies of liquid-crystal (LC) droplets and subsequent demonstration of biological reactions using such assemblies still remain elusive. Here, we show reversible and reconfigurable one-dimensional (1D) assemblies of protein-bioconjugate-sequestered monodisperse LC droplets by combining microfluidics with noninvasive acoustic wave trapping technology. Tunable spatial geometries and lattice dimensions can be achieved in an aqueous medium comprising ≈19 or 62 µm LC droplets. Different assemblies of a mixed population of larger and smaller droplets sequestered with glucose oxidase (GOx) and horseradish peroxidase (HRP), respectively, exhibit spatially localized enzyme kinetics with higher initial rates of reaction compared with GOx/HRP cascades implemented in the absence of an acoustic field. This can be attributed to the direct substrate transfer/channeling between the two complementary enzymes in close proximity. Therefore, our study provides an initial step toward the fabrication of LC-based devices for biosensing applications.

Cell interactions with lipid nanoparticles possessing different internal nanostructures: Liposomes, bicontinuous cubosomes, hexosomes, and discontinuous micellar cubosomes.

HYPOTHESIS: Lyotropic liquid crystalline nanoparticles (LLCNPs) with complex internal nanostructures hold promise for drug delivery. Cubosomes, in particular, have garnered interest for their ability to fuse with cell membranes, potentially bypassing endosomal escape challenges and improving cellular uptake. The mesostructure of nanoparticles plays a crucial role in cellular interactions and uptake. Therefore, we hypothesise that the specific internal mesophase of the LLCNPs will affect their cellular interactions and uptake efficiencies, with cubosomes exhibiting superior cellular uptake compared to other LLCNPs. EXPERIMENTS: LLCNPs with various mesophases, including liposomes, cubosomes, hexosomes, and micellar cubosomes, were formulated and characterised. Their physicochemical properties and cytotoxicity were assessed. Chinese Hamster Ovarian (CHO) cells were treated with fluorescently labelled LLCNPs, and their interactions were monitored and quantified through confocal microscopy and flow cytometry. FINDINGS: The non-lamellar LLCNPs showed significantly higher cellular interactions compared to liposomes, with cubosomes exhibiting the highest level. However, there was no significant difference in relative cell uptake between cubosomes, hexosomes, and micellar cubosomes. Cell uptake experiments at 4 °C revealed the presence of an energy-independent uptake mechanism. This study provides the first comparative analysis of cellular interactions and uptake efficiencies among LLCNPs with varying mesophases, while maintaining similar size, composition, and surface charge.

Intrinsic and Dynamic Heterogeneity of Nonlamellar Lyotropic Liquid Crystalline Nanodispersions.

Nonlamellar lyotropic liquid crystalline (LLC) nanoparticles are a family of versatile nano-self-assemblies, which are finding increasing applications in drug solubilization and targeted drug delivery. LLC nanodispersions are heterogeneous with discrete nanoparticle subpopulations of distinct internal architecture and morphology, frequently coexisting with micelles and/or vesicles. Diversity in the internal architectural repertoire of LLC nanodispersions grants versatility in drug solubilization, encapsulation, and release rate. However, drug incorporation contributes to the heterogeneity of LLC nanodispersions, and on exposure to biological media, LLC nanodispersions often undergo nanostructural and morphological transformations. From a pharmaceutical perspective, coexistence of multiple types of nanoparticles with diverse structural attributes, together with media-driven transformations in colloidal characteristics, brings challenges in dissecting biological and therapeutic performance of LLC nanodispersions in a spatiotemporal manner. Here, we outline innate and acquired heterogeneity of LLC nanodispersions and discuss technological developments and alternative approaches needed to improve homogeneity of LLC formulations for drug delivery applications.

Development of Sustained Release Formulations Based on Lipid-Liquid Crystal to Control the Release of Deoxycholate: In Vitro and In Vivo Assessment.

Subcutaneous injections of phosphatidylcholine (PC), sodium deoxycholate (NADC), and a mixture of them were found to be an effective option for treating cellulite. However, it is noteworthy that the injection of NADC may result in inflammation as well as necrosis in the injection area. The preparation of a sustained release formulation based on lipid-liquid crystal that controls the release of NADC could be a potential solution to address the issue of inflammation and necrosis at the site of injection. To present a practical and validated approach for accurately determining the concentration of NADC in LLC formulations, spectrofluorimetry was used based on the International Council for Harmonization (ICH) Q2 guidelines. Based on the validation results, the fluorometric technique has been confirmed as a reliable, efficient, and economical analytical method for quantifying NADC concentrations. The method demonstrated favorable attributes of linearity, precision, and accuracy, with an r2 value of 0.999. Furthermore, it exhibited excellent interday and intraday repeatability, with RSD values below 4%. The recovery percentages ranged from 97 to 100%, indicating the method's ability to accurately measure NADC concentrations. The subcutaneous injection of the LLC-NADC demonstrated a reduction in inflammation and tissue necrosis in skin tissue, along with an increase in fat lysis within 30 days, when compared to the administration of only NADC solution. Moreover, the histopathological assessment confirmed that the use of the LLC formulation did not result in any detrimental side effects for kidney or heart tissue.

Alkylbenzoic and Alkyloxybenzoic Acid Blending for Expanding the Liquid Crystalline State and Improving Its Rheology.

Thermotropic mesogens typically exist as liquid crystals (LCs) in a narrow region of high temperatures, making lowering their melting point with the temperature expansion of the mesophase state an urgent task. Para-substituted benzoic acids can form LCs through noncovalent dimerization into homodimers via hydrogen bonds, whose strength and, consequently, the temperature region of the mesophase state can be potentially altered by creating asymmetric heterodimers from different acids. This work investigates equimolar blends of p-n-alkylbenzoic (kBA, where k is the number of carbon atoms in the alkyl radical) and p-n-alkyloxybenzoic (kOBA) acids by calorimetry and viscometry to establish their phase transitions and regions of mesophase existence. Non-symmetric dimerization of acids leads to the extension of the nematic state region towards low temperatures and the appearance of new monotropic and enantiotropic phase transitions in several cases. Moreover, the crystal-nematic and nematic-isotropic phase changes have a two-step character for some acid blends, suggesting the formation of symmetric and asymmetric associates from heterodimers. The mixing of 6BA and 8OBA most strongly extends the region of the nematic state towards low temperatures (from 95-114 °C and 108-147 °C for initial homodimers, respectively, to 57-133 °C for the resulting heterodimer), whereas the combination of 4OBA and 5OBA gives the most extended high-temperature nematic phase (up to 156 °C) and that of 6BA and 9OBA (or 12OBA) provides the existence of a smectic phase at the lowest temperatures (down to 51 °C).

Lyotropic liquid crystalline 2D and 3D mesophases: Advanced materials for multifunctional anticancer nanosystems.

Cancer remains a leading cause of mortality. Despite significant breakthroughs in conventional therapies, treatment is still far from ideal due to high toxicity in normal tissues and therapeutic inefficiency caused by short drug lifetime in the body and resistance mechanisms. Current research moves towards the development of multifunctional nanosystems for delivery of chemotherapeutic drugs, bioactives and/or radionuclides that can be combined with other therapeutic modalities, like gene therapy, or imaging to use in therapeutic screening and diagnosis. The preparation and characterization of Lyotropic Liquid Crystalline (LLC) mesophases self-assembled as 2D and 3D structures are addressed, with an emphasis on the unique properties of these nanoassemblies. A comprehensive review of LLC nanoassemblies is also presented, highlighting the most recent advances and their outstanding advantages as drug delivery systems, including tailoring strategies that can be used to overcome cancer challenges. Therapeutic agents loaded in LLC nanoassemblies offer qualitative and quantitative enhancements that are superior to conventional chemotherapy, particularly in terms of preferential accumulation at tumor sites and promoting enhanced cancer cell uptake, lowering tumor volume and weight, improving survival rates, and increasing the cytotoxicity of their loaded therapeutic agents. In terms of quantitative anticancer efficacy, loaded LLC nanoassemblies reduced the IC50 values from 1.4-fold against lung cancer cells to 125-fold against ovarian cancer cells.

The influence of mannose-based esters on the mesophase behaviour of lyotropic liquid crystalline nanosystems as drug delivery vectors.

Lyotropic Liquid Crystalline (LLC) nanoparticles represent an emerging class of smart, biocompatible, and biodegradable systems for the delivery of drugs. Among these, structures with complex 3D architectures such as cubosomes are of particular interest. These are non- lamellar assemblies having hydrophobic and hydrophilic portions able to carry drugs of different nature. They can further be modulated including suitable additives to control the release of the active payload, and to promote an active targeting. Starting from monoolein (GMO) cubic phase, different concentrations of mannose-based esters were added, and the eventual structural modifications were monitored to ascertain the effects of the presence of glycolipids. Moreover, the structural properties of these nanosystems loaded with Dexamethasone (DEX), a very well-known anti-inflammatory steroid, were also studied. Experiments were carried out by synchrotron Small Angle X-ray Scattering (SAXS), Raman Microspectroscopy (RMS) and Attenuated Total Reflectance-Fourier Transform Infrared (ATR-FTIR) measurements. The drug delivery potential (i.e. entrapment efficiency and release properties) of the obtained nanoparticles was evaluated. Finally, in vitro cytocompatibility and anti-inflammatory activity studies of the prepared formulations were carried out. Inclusion of mannose-based surfactants up to 10 mol% influenced the structural parameters of Im3m cubic phase and swollen cubic phases were obtained with the different glycolipids with lattice parameters significantly higher than GMO. A complete cytocompatibility and an increased DEX activity were observed, thus suggesting the possibility to use GMO/glycolipids nanoparticles to formulate innovative drug delivery systems.

Harnessing Liquid Crystal Sensors for High-Throughput Real-Time Detection of Structural Changes in Lysozyme during Refolding Processes.

Despite the rapid advances in process analytical technology, the assessment of protein refolding efficiency has largely relied on off-line protein-specific assays and/or chromatographic procedures such as reversed-phase high-performance liquid chromatography and size exclusion chromatography. Due to the inherent time gap pertaining to traditional methods, exploring optimum refolding conditions for many recombinant proteins, often expressed as insoluble inclusion bodies, has proven challenging. The present study describes a novel protein refolding sensor that utilizes liquid crystals (LCs) to discriminate varying protein structures during unfolding and refolding. An LC layer containing 4-cyano-4'-pentylbiphenyl (5CB) intercalated with 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) is used as a sensing platform, and its proof-of-concept performance is demonstrated using lysozyme as a model protein. As proteins unfold or refold, a local charge fluctuation at their surfaces modulates their interaction with zwitterionic phospholipid DOPE. This alters the alignment of DOPE molecules at the aqueous/LC interface, affecting the orientational ordering of bulk LC (i.e., homeotropic to planar for refolding and planar to homeotropic for unfolding). Differential polarized optical microscope images of the LC layer are subsequently generated, whose brightness directly linked to conformational changes of lysozyme molecules is quantified by gray scale analysis. Importantly, our LC-based refolding sensor is compatible with diverse refolding milieus for real-time analysis of lysozyme refolding and thus likely to facilitate the refolding studies of many proteins, especially those lacking a method to determine structure-dependent biological activity.

Lyotropic liquid crystalline phases: Drug delivery and biomedical applications.

Liquid crystal (LC)-based nanoformulations may efficiently deliver drugs and therapeutics to targeted biological sites. Lyotropic liquid crystalline phases (LLCPs) have received much interest in recent years due to their unique structural characteristics of both isotropic liquids and crystalline solids. These LLCPs can be utilized as promising drug delivery systems to deliver drugs, proteins, peptides and vaccines because of their improved drug loading, stabilization, and controlled drug release. The effects of molecule shape, microsegregation, and chirality are very important in the formation of liquid crystalline phases (LCPs). Homogenization of self-assembled amphiphilic lipids, water and stabilizers produces LLCPs with different types of mesophases, bicontinuous cubic (cubosomes) and inverse hexagonal (hexosomes). Moreover, many studies have also shown higher bioadhesivity and biocompatibility of LCs due to their structural resemblance to biological membranes, thus making them more efficient for targeted drug delivery. In this review, an outline of the engineering aspects of LLCPs and polymer-based LLCPs is summarized. Moreover, it covers parenteral, oral, transdermal delivery and medical imaging of LC in targeting various tissues and is discussed with a scope to design more efficient next-generation novel nanosystems. In addition, a detailed overview of advanced liquid crystal-based drug delivery for vaccines and biomedical applications is reviewed.