Lyotropic Liquid Crystal System Research Articles

Lyotropic liquid crystal and self-emulsifying drug delivery systems nanoparticles as artesunic acid and praziquantel carriers: An innovative approach for formulation of anti-malaria and schistosomicidal drugs

Praziquantel (PZQ) is the drug of choice for treating cestode and trematode infections, and it is currently the only option against schistosomiasis. Artesunic acid (AcART) is effective against several parasites and has emerged as an alternative for schistosomiasis treatment. However, AcART and PZQ have limited bioavailability due to poor water solubility, low permeability, and rapid cell clearance. To address these challenges, this study aimed to develop self-emulsifying drug delivery systems to develop SEDDS and NPs-LLC to overcome the low water solubility affecting AcART and PZQ bioavailability. The study involved validating the HPLC analytical methodology for AcART, SEDDS, and NPs-LLC formulations, and conducting physicochemical characterization and ex-vivo intestinal permeation assays. The composition of formulations was determined by the solubility balance of AcART and PZQ. The drug content ranged between 83 and 90 %. The anionic zeta potential was attributed to Myverol®, and the particle diameter increased slightly after the drug incorporation, while the polydispersity index indicated the relatively narrow particle size distribution. Additionally, the DSC thermogram confirmed that PZQ and AcART are in solution within SEDDS and NPs-LLC. The FTIR analysis suggests that components of SEDDS and NPs-LLC and drugs do not react to form new chemical species. The selection of specific compound formulations was based on achieving the best solubility balance. The nanostructures were stable and exhibited a surface charge favorable to mucosal permeation, with slightly superior performance for SEDDS. The innovative formulations, SEDDS and NPs-LLC, are suitable and effective carriers for AcART and PZQ.

Phase behavior and biological activity of lyotropic liquid crystal systems doped with 1,2,3-triazole derivative

Heterocyclic compounds are important for the synthesis of pharmaceuticals, especially substituted triazoles, which have high biological activity. The development of approaches to the creation of delivery systems for bioactive heterocyclic compounds is of particular importance for improving the biopharmaceutical aspects of therapy. In this work, we report synthesis and characterization of a new 1,2,3-triazole: ethyl 2-((1-decyl-1H-1,2,3-triazol-4-yl)methyl)-3-oxobutanoate (TR). The efficient incorporation into lyotropic mesophases as a drug delivery platform demonstrated. Polarized optical microscopy studies confirmed formation of a lyotropic mesophase in the binary P123/TR system as well as in tertiary systems with added water, ethanol, and DMSO. This allows to dope 5 % of triazole into lyomesophases. IR and UV spectroscopy studies detected intermolecular interactions occurring in the P123/TR system. Release of TR from binary and tertiary lyomesophases was studied. Impacts of composition and temperature on the release time were analyzed. Evaluation of cytotoxicity to M-Hela and HuTu-80 cancer lines and Chang Liver living cells revealed antitumor properties of the studied substituted 1,2,3-triazole. The lowest IC50 of TR is 57 μg·mL−1 toward HuTu-80. This is at the level of the reference drug Fluconazol. For the P123/DMSO/TR LLC system in concentration range of 31.3–124 µg·ml−1, the viability percentage of liver cells is comparable to those of cancer cells. These results demonstrate the potential opportunity for application LLC P123/DMSO used as a TR delivery for and enhance its antitumor effect.

Acoustic levitation combined with laboratory-based small-angle X-ray scattering (SAXS) to probe changes in crystallinity and molecular organisation.

Single particle levitation techniques allow us to probe samples in a contactless way, negating the effect that surfaces could have on processes such as crystallisation and phase transitions. Small-angle X-ray scattering (SAXS) is a common method characterising the nanoscale order in aggregates such as colloidal, crystalline and liquid crystalline systems. Here, we present a laboratory-based small-angle X-ray scattering (SAXS) setup combined with acoustic levitation. The capability of this technique is highlighted and compared with synchrotron-based levitation-SAXS and X-ray diffraction. We were able to follow the deliquescence and crystallisation of sucrose, a commonly used compound for the study of viscous atmospheric aerosols. The observed increased rate of the deliquescence-crystallisation transitions on repeated cycling could suggest the formation of a glassy sucrose phase. We also followed a reversible phase transition in an oleic acid-based lyotropic liquid crystal system under controlled humidity changes. Our results demonstrate that the coupling of acoustic levitation with an offline SAXS instrument is feasible, and that the time resolution and data quality are sufficient to draw physically meaningful conclusions. There is a wide range of potential applications including topics such as atmospheric aerosol chemistry, materials science, crystallisation and aerosol spray drying.

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.

Fabricating supramolecular lyotropic crystals at subzero temperatures: The pivotal role of antifreeze and nanostructures

The classical lyotropic liquid crystals (LLCs) prepared in pure water are not adapted to subzero temperatures. However, the fabrication of cryogenic LLCs is highly significant for gaining profound insights into self-assembly at extremely low temperatures. A proficient solution strategy, namely introducing alcohol antifreeze to water, faces a challenge in balancing frozen resistance and efficient self-assembly. Herein, we address this unmet challenge by selecting four alcohols with comparable structure to fabricate cryogenic LLCs system through the supramolecular self-assembly of a long-chain non-ionic surfactant. The freezing point, surfactant solubility, and self-assembly behavior at subzero temperatures were investigated. The alcohol antifreeze plays a significant role in depressing water freezing point and governing assembled microstructures. Both experimental and computational results revealed that alcohols bearing more hydroxyl groups are efficient to lower water freezing point while remain the capability to induce surfactant self-assembly. They can realize solvophobic balance and strong hydrogen-bond interactions. A simple approach based on Gordon parameter was established to evaluate the suitability as an anti-freezing medium for amphiphile self-assembly. Strikingly, a new LLCs system capable of withstanding the extremely low temperature of −80 °C was developed, which shows interestingly continuous phase transitions as temperature lowers to subzero. Overall, this study provides valuable insights into cryogenic supramolecular self-assembly, and offers a significant foundation and evaluation method for the selection of appropriate alcohol antifreeze for cryogenic self-assembly.

Influence of Ionic Liquid and Light Intensity on a Polymer Nanostructure Formed in Lyotropic Liquid Crystalline Templates.

Utilizing self-assembled lyotropic liquid crystal (LLC) templates with radical photopolymerization shows promise in controlling polymer structure on the nanometer scale This control of nanostructure allows tailoring and enhancement of material properties not attainable in traditional polymerization in applications including hydrogels and stimuli-responsive systems. However, thermodynamically driven phase separation between the polymer and LLC templates often hinders the control of local polymer order and resultant polymer properties. This study investigates an alternative method to control the hydrogel nanostructure and avoid phase separation using imidazolium ionic liquids (ILs) in the LLC template while modulating the light intensity used in photopolymerization. The addition of the IL improves the thermodynamic stability and enhances the polymerization rate in the LLC system. The degree of LLC nanostructure retention is increased by increasing light intensities during polymerization. In addition, intermediate concentrations of cross-linker allow a balance between phase stability and cross-linking to lock in LLC morphology. With enhanced retention, the maximum water uptake is significantly higher compared with isotropic controls. These results demonstrate a method to increase the structure on the nanometer scale of a polymer by combining the addition of ILs with the proper selection of light intensity and cross-link density that allows access to unique hydrogel properties. These templated polymers demonstrate enhanced swelling and a stimuli response that show promise in applications ranging from drug delivery to water remediation.

Lamellar liquid crystals formed from sucrose ester and Brij97 solutions for curcumin delivery

Abstract In this paper, the lamellar liquid crystals formed in S1570-Brij97/isopropyl myristate/PEG400 aqueous system were prepared at 37 °C. The effects of PEG400 and curcumin on the S1570-Brij97 lyotropic liquid crystal systems were studied by phase diagram, polarized optical microscopy, small angle X-ray scattering, and rheology. The prepared lamellar liquid crystals show stable structures at 37 °C. The encapsulation of curcumin improves the structural stability of the lamellar liquid crystals, which can be confirmed by their higher η γ=0.013 and σ y values, suggesting that the S1570-Brij97 lamellar liquid crystals are good carriers for curcumin. In addition, the prepared lamellar liquid crystals can effectively protect curcumin from decomposition, and curcumin can be released slowly in the liquid crystals. Therefore, based on the structural stability, protective effect on curcumin, and slow-release behavior, the constructed S1570-Brij97 lamellar liquid crystals have good potential for drug delivery.

Antimicrobial peptide dendrimers assisted Nanocomposite-Loaded lyotropic liquid crystalline for multimodal surgical site infection management

Superficial incisional surgical site infections (SISSIs) were a serious challenge leading to delayed wound healing and even systemic diseases. The high incidence of antibiotic resistance and unprotected wound lesions severely hindered the current therapeutical efficiency. In this study, an antibacterial nanocomposite PAMAM-PLL@AuNPs was designed to avoid antibiotic resistance, and a lyotropic liquid crystal system was used for local drug delivery and protecting lesions. The PAMAM-PLL was constructed with polyamide amine (PAMAM) as the core and polylysine (PLL) as the branch chain, which increased the antibacterial activity by 4 times. After being connected to gold nanoparticles (AuNPs), a further 2 times antibacterial activity improvement was achieved. PAMAM-PLL@AuNPs could eliminate bacteria by multimodal mechanisms, including causing leakage of intracellular substances, inducing intracellular reactive oxygen species and inhibiting bacterial metabolism. Thanks to their spontaneous phase transition and the mechanical response characteristics of the lattice structure, lyotropic liquid crystal with self-healing characteristics was employed to load PAMAM-PLL@AuNPs. The unique structure facilitated buffering external forces and accelerated wound healing. The excellent antibacterial and wound healing properties of the lyotropic liquid crystal drug delivery system were confirmed by a surgical incision infection model. This study is expected to provide a robust strategy for the treatment of SISSIs.

Application of Low-Frequency Raman Spectroscopy to Probe Dynamics of Lipid Mesophase Transformations upon Hydration

Low-frequency Raman (LFR) spectroscopy is presented as a viable tool for studying the hydration characteristics of lyotropic liquid crystal systems herein. Monoolein was used as a model compound, and its structural changes were probed both in situ and ex situ which enabled a comparison between different hydration states. A custom-built instrumental configuration allowed the advantages of LFR spectroscopy to be utilized for dynamic hydration analysis. On the other hand, static measurements of equilibrated systems (i.e., with varied aqueous content) showcased the structural sensitivity of LFR spectroscopy. The subtle differences not intuitively observed between similar self-assembled architectures were distinguished by chemometric analysis that directly correlated with the results from small-angle X-ray scattering (SAXS), which is the current "gold standard" method for determining the structure of such materials.

Lyotropic Liquid Crystal System for Drug Delivery of Astaxanthin: Physical Characterization and Enhanced Antioxidant Potential

Astaxanthin is a xanthophyll carotenoid, well known for its potent anti-inflammatory and antioxidant properties, owing to its unsaturated molecular structure. Aquatic plants and animals contain the hydrophobic carotenoid astaxanthin, which is thought to possess a number of advantageous biological traits. However, due to its weak bioavailability and low water solubility, its use as a nutraceutical in food is currently restricted. Cubosomal encapsulation has been considered an effective alternative for improving the bioavailability and solubility of hydrophobic bioactives. The current paper aimed to conquer these issues by encapsulating astaxanthin in lyotropic liquid crystal nano-formulations prepared via the fabrication method. The physicochemical properties of astaxanthin-loaded cubosomes (AST-LC) have also been analyzed, in order to know the morphology of the prepared formulations and their bioavailability in the biological system. The formulation has been tested for particle size, thermal behavior, zeta potential, crystallinity, encapsulation efficiency, and drug-polymer interactions. The observed experimental results showed the particle size and zeta potential of astaxanthin-loaded cubosomes (AST-LC) as 199 ± 0.23 nm −27.4 ± 4.67 mV, with a small polydispersity index (0.283 ± 1.01). The cubic structure and nano-range size of the ideal formulation were verified by a field emission scanning electron microscope (FESEM) and (HRTEM) high-resolution transmission electron microscopic examination. The formulation exhibits a higher encapsulation efficiency with good yield. Results from X-ray diffraction and diffraction scanning calorimetry demonstrated an amorphous state of astaxanthin incorporated into the formulation. Fourier transform infrared spectroscopy (FTIR) analysis of AST-LC showed the absence of astaxanthin main peaks, indicating its complete encapsulation inside the formulation. The drug–excipient interaction was carried out with diffraction scanning calorimetry DSC and FTIR, resulting in no interaction between them. These results offered important details about increasing astaxanthin bioavailability by incorporating it into cubosomes. Furthermore, the astaxanthin loaded into cubosomes has been evaluated for antioxidant potency, compared with astaxanthin extract using 2,2-diphenylpicrylhydrazylassay (DPPH assay).

Lyotropic liquid crystals for parenteral drug delivery

The necessity for long-term treatments of chronic diseases has encouraged the development of novel long-acting parenteral formulations intending to improve drug pharmacokinetics and therapeutic efficacy. Lately, one of the novel approaches has been developed based on lipid-based liquid crystals. The lyotropic liquid crystal (LLC) systems consist of amphiphilic molecules and are formed in presence of solvents with the most common types being cubic, hexagonal and lamellar mesophases. LC injectables have been recently developed based on polar lipids that spontaneously form liquid crystal nanoparticles in aqueous tissue environments to create the in-situ long-acting sustained-release depot to provide treatment efficacy over extended periods. In this manuscript, we have consolidated and summarized the various type of liquid crystals, recent formulation advancements, analytical evaluation, and therapeutic application of lyotropic liquid crystals in the field of parenteral sustained release drug delivery.

Applicability of Chlorpromazine.HCl- lyotropic nanosystems into photogalvanic cells

This paper reports on the development of liquid crystal for the electrochemical study of photo-induced electron transfer. This study covers the following studies: the description of the laminar liquid crystals (LLCs) system by using CPZ.HCl material, examining the lyotropic liquid crystal system of CPZ.HCl compound and its application in the photogalvanic cell. Chlorpromazine hydrochloride (CPZ.HCl) was first shown to form a lyotropic liquid crystal (LLC) when the concentrations reached > 10 M in an aqueous solution. This self-assembly was revealed through the birefringence observed through cross-polarisers and the characteristic X-ray scattering. The electrochemistry of the CPZ.HCl- LLC system was probed through the use of cyclic voltammetry using different micro-electrode materials, diameters and CPZ.HCl concentrations. Following this, this system was fabricated into a photogalvanic cell that produced a power conversion efficiency (PCE) of 0.58 %.

Investigation of structural changes in the liquid crystal system AOT / n–heptane–water under the influence of vitamin E by the method of X–ray analysis

Structural rearrangements of the lyotropic liquid–crystal system sodium salt of di–(2–ethylhexyl) ester of sulfosuccinic acid (AOT) –n–heptane – water under the influence of vitamin E were studied by X–ray diffraction. The studies were carried out in the concentration range from 50 to 80% AOT+E in a mixed solvent n–heptane/water. The studies were carried out with a gradual increase in the concentration of vitamin E in the system and with an increase in the concentration of AOT + E in a solution of n–heptane/water. It has been established that, in the model liquid crystal system under study, vitamin E penetrating into the structure of the liquid crystal phase AOT–n–heptane–water leads to structural rearrangements and compactization of the molecular packing of the “smooth” phase.

An extensive analysis of isodesmic assembly in dilute solutions of two lyotropic chromonic liquid crystal systems

ABSTRACT Lyotropic chromonic liquid crystal (LCLC) molecules spontaneously assemble into anisotropic structures. Here, the behaviour of LCLC molecules in aqueous solutions is investigated to test whether the assembly process in two different systems is isodesmic. Dilute solutions are required for such a test, so this work focuses on changes in the UV and visible absorption spectra for DSCG and SSY solutions with concentrations no greater than 0.5 wt%, which are always in the isotropic phase. Unlike prior investigations of these systems, the complicated absorption spectra are decomposed into simple absorbance peaks prior to analysis. In addition, two slightly different models of isodesmic assembly and two different analysis methods of the absorption spectra are utilised. Not all of the new experimental results are consistent with prior work, but in the end the analyses confirm that an isodesmic process is an appropriate model for these LCLC systems.

An Injectable In Situ Depot-Forming Lipidic Lyotropic Liquid Crystal System for Localized Intratumoral Drug Delivery.

To address the need for localized chemotherapy against unresectable solid tumors, an injectable in situ depot-forming lipidic lyotropic liquid crystal system (L3CS) is explored that can provide spatiotemporal control over drug delivery. Although liquid crystals have been studied extensively before but their application as an injectable intratumoral depot system for locoregional chemotherapy has not been explored yet. The developed L3CS in the present study is a low-viscosity injectable fluid having a lamellar phase, which transforms into a hexagonal mesophase depot system on subcutaneous or intratumoral injection. The transformed depot system can be preprogrammed to provide tailored drug release intratumorally, over a period of one week to one month. To establish the efficacy of the developed L3CS, doxorubicin is used as a model drug. The drug release mechanism is studied in detail both in vitro and in vivo, and the efficacy of the developed system is investigated in the murine 4T1 tumor model. The direct intratumoral injection of the L3CS provided localized delivery of doxorubicin inside the tumor and restricted its access within the tumor only for a sustained period of time. This led to an over 10-fold reduction in tumor burden, reduced cardiotoxicity, and a significant increase in the median survival rate, compared to the control group. The developed L3CS thus provides an efficient strategy for localized chemotherapy against unresectable solid tumors with a great degree of spatial and temporal control over drug delivery.

Exploring the affluent potential of glyceryl mono oleate – myristol liquid crystal nanoparticles mediated localized topical delivery of Tofacitinib: Study of systematic QbD, skin deposition and dermal pharmacokinetics assessment

This study aimed to design and characterize Tofacitinib (TF)-loaded lyotropic liquid crystalline nanoparticles (TF-LCNP) gel using quality by design-driven approach to enhance the skin delivery of TF. The present work investigated the impact of two different liquid lipids on different critical quality attributes of LCNP. The optimized lyotropic liquid crystals system was constructed with the glyceryl monooleate,myristol, Lutrol® and water system. The optimized TF - LCNP showed particle size of 74.82 ± 4.26 nm, polydispersity index of 0.124 ± 0.024, and entrapment efficiency of 68.29 ± 5.24 %. The TF-LCNP showed sustained release for 24 h and followed quasi-Fickian diffusion from non-swellable matrix diffusion with n value of 0.197. The ex vivo permeation studies exhibited that amount of TF permeated through LCNP gel and cream after 24 h were found to be 61.11 ± 1.5 µg/cm2 and 37.7 ± 3.5 µg/cm2, respectively. The penetration mechanism of TF-LCNP gel through skin layers followed the Korsmeyer- Peppas model (n-value of 1.687), indicated Case-II relaxational release of TF. The tape stripping studies showed that TF loaded LCNPs retained 3 fold and 2.81 fold greater TF in stratum corneum and viable skin layers than conventional cream. The coumarin – 6 loaded LCNP study using Fluorescence microscopy confirmed the penetration of TF-LCNP into the deeper layers of skin. The dermal pharmacokinetic studies revealed that the LCNP showed a steady equilibrium state in 5–8 h in epidermis and dermis layers. The total amount of TF permeated with developed LCNP formulation was 3.42 times and 2.19 times higher in epidermis and dermis compared to the TF-cream. The developed formulation exhibited good spreadability and rheology and has not shown any significant changes in stability and scale-up studies. In a nutshell, the developed TF-LCNP strategy poses excellent potential in targeting the viable skin layer.

Characterization of hexagonal lyotropic liquid crystal microstructure: Effects of vitamin E molecules

The effects of vitamin E (VE) on the liquid crystal behavior and structure of a lyotropic liquid crystal (LLC) system based on nonionic surfactant C12EO10/H2O are reported. Polarized optical microscopy, X-ray diffraction and FTIR combined with fluorescent analysis were utilized to study structural properties and the interactions between the vitamin E and hexagonal mesophase. It was revealed that up to 20 wt% VE is solubilized within the direct hexagonal mesophase. As a result, the lattice parameter and the melting point increased as compared with binary LLC C12EO10/H2O. The presence in the system C12EO10/H2O of VE in the amount above 30% (up to 60 wt%) leads to a structural transformation of the mesophase from the direct to reverse hexagonal mesophase. The structural changes of hydrophilic and hydrophobic domains in the presence of VE in LLC were characterized.

Temperature-sensitive lyotropic liquid crystals as systems for transdermal drug delivery

The purpose of this study was to develop temperature-sensitive lyotropic liquid crystals (LLC) for transdermal drug delivery systems. The hexagonal and cubic LLC samples were constructed in the polyoxyethylene (20) sorbitan monooleate (Tween 80)/PEG-60 hydrogenated castor oil (RH 60)/Ethyl oleate (EtOL)/water (H2O) system and characterized by Small Angle X-ray Scattering (SAXS), low field nuclear magnetic resonance (LF-NMR) and rheology. Additionally, its skin permeation behavior in vitro and cell-stimulating studies were investigated as well. The LLC system exhibited temperature sensitivity. Under the influence of temperature, the structure of LLC collapsed and was transformed into micellar solution. While, sample S3 (water content was 35 wt%.) was transformed from cubic LLC to hexagonal LLC then to micellar solution as temperature increased. The compositions and the introduction of paeonol both can influence the structure of LLC, and were used to adjust the phase transition temperature to close to the human body temperature. In vitro transdermal experiments showed that the release behavior of paeonol-loaded LLC was obviously temperature-sensitive and controlled by concentration diffusion. In vitro cell-stimulating studies displayed that LLC samples exhibited no obvious toxicity. The above results indicated that the temperature-sensitive LLC had potential to be applied as a transdermal drug delivery system.

Tuneable interfacial surfactant aggregates mimic lyotropic phases and facilitate large scale nanopatterning.

It is shown that the air-liquid interface can be made to display the same rich curvature phenomena as common lyotropic liquid crystal systems. Through mixing an insoluble, naturally occurring, branched fatty acid, with an unbranched fatty acid of the same length, systematic variation in the packing constraints at the air-water interface could be obtained. The combination of atomic force microscopy and neutron reflectometry is used to demonstrate that the water surface exhibits significant tuneable topography. By systematic variation of the two fatty acid proportions, ordered arrays of monodisperse spherical caps, cylindrical sections, and a mesh phase are all observed, as well as the expected lamellar structure. The tuneable deformability of the air-water interface permits this hitherto unexplored topological diversity, which is analogous to the phase elaboration displayed by amphiphiles in solution. It offers a wealth of novel possibilities for the tailoring of nanostructure.

Single experiment measurement of residual dipolar couplings in aqueous solution using a biphasic bisperylene imide chromonic liquid crystal

The use of the biphasic isotropic/nematic region in a bisperylene imide-based lyotropic liquid crystal system allows the extraction of proton-carbon 1 DCH residual dipolar couplings in aqueous solution from a single F1-coupled HSQC experiment. The method was successfully applied to the RDC-based conformational analysis of sucrose.