Influence of the emulsifier on nanostructure and clinical application of liquid crystalline emulsions.

Liquid crystals are appealing in pharmaceutical and cosmetic fields due to their unique structures that combine the properties of both liquid and solid states. Forming an emulsion into liquid crystals can be affected by a number of factors, including the emulsion composition and temperature. Changing the types and concentrations of surfactants could be another factor that affects liquid crystals. Currently, most liquid crystal research focuses on the nanostructure of liquid crystal systems without evaluating the efficacy of liquid crystals clinically. In this study, liquid crystalline emulsions made from camellia seed oil with four different surfactants (Olivem 1000, Polyaquol-2W, Nikkomulese LC, and Lecinol S-10 with Tween 80) were created. The liquid crystal emulsions were formulated in the form of oil-in-water (o/w) emulsions with Camellia oleifera seed oil serving as the main ingredient in the oil phase (10% w/w). All formulations exhibited liquid crystal characteristics with lamellar structures as determined by the polarized light microscopy and small-angle X-ray scattering with supporting data of the nanostructure from wide-angle X-ray scattering and differential scanning calorimetry (DSC). They all showed good stability under normal (room temperature) and accelerated conditions (4 °C and 40 °C) in long-term storage (6 months). Using the reconstructed human epidermis as a skin model, all formulations did not cause skin irritation. In the clinical trial, all formulations were able to reduce transepidermal water loss (TEWL) and increase skin hydration immediately after application. This lasted at least 10 h. All formulations showed distinct Maltese crosses under the polarized light microscope with a positive result for liquid crystals in wide angle X-ray scattering (WAXS) and small angle X-ray scattering (SAXS) methods. Moreover, among all formulations tested, Formulation D, which contained Lecinol S-10 and Tween 80 as emulsifiers, showed the most robust interaction between the surfactant and water molecules in the lamellar structure under DSC. The formulation was stable in long-term normal and accelerated conditions. Above all, Formulation D, which was formulated with Lecinol S-10 with Tween 80, had the best clinical result, was nonirritating to the skin, and can be used as a cream base in the pharmaceutical and cosmeceutical sectors.

Liquid-Crystalline Order in the Phosphorus-Containing DenDrimers.

The structure of phosphorus-containing dendrimers has been studied by IR spectroscopy and optical polarization microscopy. The repeating units of dendrimer molecules are mesogens. This property arises from the conjugation of the aromatic ring and the hydrazone group. An analysis of the IR spectra showed that, with an increase in the generation number, the width of the stretching vibration bands ν(PN) and ν(PO) increases. Difficulties in packing molecules of higher generations cause conformational diversity. The shape of the dendrimer molecules was determined by analyzing the increments of dipole moments. Additionally, the modeling of the stacking of repeating links was performed. The spherical model of molecules does not satisfy the experimental dipole moments of the dendrimers. The flat disk model is more suitable for explaining step changes in dipole moments. The liquid-crystalline ordering of dendrimers under the action of applied pressure was found. With simultaneous heating and uniaxial compression, optical anisotropy appears in dendrimers. It is associated with the formation of liquid-crystalline order. However, a thermodynamically stable liquid-crystalline phase is not formed in this case. Dendrimers most likely have disk-shaped molecules.

Topical gel based nanoparticles for the controlled release of oleanolic acid: design and in vivo characterization of a cubic liquid crystalline anti-inflammatory drug.

BACKGROUND: Oleanolic acid (OA) has multiple pharmaceutical applications including anti-inflammatory activity, but low permeability of the molecule limits its widespread use. METHODS: A cubic liquid crystalline nanoparticle (LCNP)-based gel was prepared as a potential topical delivery system for OA. The LCNP-based gel was optimized using rheological, drug release kinetic, and ex vivo permeation studies. RESULTS: The studies showed that the OA was trapped in the interior of the LCNP with a crystal form of Pn3m space. The optimized LCNP formulation performed well using in vitro release studies for up to 12 h (85.49 ± 0.21%). Ex vivo permeation studies showed that the LCNP-based gel formulation was superior to a standard gel formulation. The r2 value from the Peppas equation indicated good linearity, but showed irregular (non-Fickian) diffusion, suggesting that drug release was controlled by multiple processes. CONCLUSIONS: In this study, OA-loaded LCNPs were prepared by the precursor method, resulting in a well-characterized OA-LCNP gel preparation. The gel was shown to be effective in a rodent carrageenan-induced hind paw inflammation model with sustained efficacy after a single application.

Preparation, Synergism, and Biocompatibility of in situ Liquid Crystals Loaded with Sinomenine and 5-Fluorouracil for Treatment of Liver Cancer.

PURPOSE: Transarterial chemoembolization is the preferred treatment for patients with middle and advanced-stage hepatocellular carcinoma (HCC); however, most hepatic artery embolization agents have various disadvantages. The purpose of this study was to evaluate phytantriol-based liquid crystal injections for potential use in treatment of HCC. METHODS: Using sinomenine (SN) and 5-fluorouracil (5-FU) as model drugs, three precursor in situ liquid crystal injections based on phytantriol (P1, P2, and P3) were prepared, and their in vitro biocompatibility, anticancer activity, and drug release investigated, to evaluate their feasibility for use in treatment of HCC. The properties of the precursor injections and subsequent cubic liquid crystal gels were observed by visual and polarizing microscopy, in an in vitro gelation experiment. Biocompatibility was evaluated by in vitro hemolysis, histocompatibility, and cytotoxicity assays. RESULTS: Precursor injections were colorless liquids that formed transparent cubic liquid crystal gels on addition of excess water. The three precursor injections all caused slight hemolysis, without agglutination, and were mildly cytotoxic. Histocompatibility experiments showed that P1 had good histocompatibility, while P2 and P3 resulted in strong inflammatory responses, which subsequently resolved spontaneously. In vitro anti-cancer testing showed that SN and 5-FU inhibited HepG2 cells in a time- and concentration-dependent manner and had synergistic effects. Further, in vitro release assays indicated that all three preparations had sustained release effects, with cumulative release of >80% within 48 h. CONCLUSION: These results indicate that SN and 5-FU have synergistic inhibitory effects on HepG2 cells, which has not previously been reported. Moreover, we describe a biocompatible precursor injection, useful as a drug carrier for the treatment of liver cancer, which can achieve targeting, sustained release, synergistic chemotherapy, and embolization. These data indicate that precursor injections containing SN and 5-FU have great potential for use in therapy for liver cancer.

Formulation of Novel Liquid Crystal (LC) Formulations with Skin-Permeation-Enhancing Abilities of Plantago lanceolata (PL) Extract and Their Assessment on HaCaT Cells.

Exposure to reactive oxygen species can easily result in serious diseases, such as hyperproliferative skin disorders or skin cancer. Herbal extracts are widely used as antioxidant sources in different compositions. The importance of antioxidant therapy in inflammatory conditions has increased. Innovative formulations can be used to improve the effects of these phytopharmacons. The bioactive compounds of Plantago lanceolata (PL) possess different effects, such as anti-inflammatory, antioxidant, and bactericidal pharmacological effects. The objective of this study was to formulate novel liquid crystal (LC) compositions to protect Plantago lanceolata extract from hydrolysis and to improve its effect. Since safety is an important aspect of pharmaceutical formulations, the biological properties of applied excipients and blends were evaluated using assorted in vitro methods on HaCaT cells. According to the antecedent toxicity screening evaluation, three surfactants were selected (Gelucire 44/14, Labrasol, and Lauroglycol 90) for the formulation. The dissolution rate of PL from the PL-LC systems was evaluated using a Franz diffusion chamber apparatus. The antioxidant properties of the PL-LC systems were evaluated with 2,2-diphenyl-1-picrylhydrazyl (DPPH) and malondialdehyde (MDA) assessments. Our results suggest that these compositions use a nontraditional, rapid-permeation pathway for the delivery of drugs, as the applied penetration enhancers reversibly alter the barrier properties of the outer stratum corneum. These excipients can be safe and highly tolerable thus, they could improve the patient's experience and promote adherence.

Associating chitosan and microemulsion as a topical vehicle for the administration of herbal medicines.

A viscous solution of low molecular weight chitosan (CH) at 5% w/v (10.2 kDa, 75 % deacetylated, 1451 cP at 25 °C) was associated with a microemulsion (ME) that undergoes a phase transition after water absorption in situ (≈28 % w/w), forming a more viscous liquid crystal, which was potentially evaluated as a topical vehicle. The ME was selected from a phase diagram, selecting a composition based on Tween® 80 (52 %), myristate isopropyl (28 %), and the aqueous phase (water and polyethylene glycol 400, 60:40 w/w) (20 %), which was after replaced by CH and herbal medicines (HM). HM are alternatives to treat candidiasis, and Stryphnodendron adstringens shell extract, characterized by molecular networking, and Melaleuca alternifolia Chell essential oil (46 % of terpinen-4-ol), showed in vitro activity against Candida albicans. Associating CH in ME improved the mechanical properties of the topical formulation, as adhesiveness, which is an advantageous feature for the topical treatment of vulvovaginal candidiasis.

Isolation and characterization of nanocellulose crystals via acid hydrolysis from agricultural waste-tea stalk.

Nanocellulose crystals (NCCs) were successfully prepared via acid hydrolysis from an abundant agricultural waste (tea stalk) in China. The effective factors for NCC yield were modeled by the response surface methodology (RSM). The RSM determined the reaction conditions (H2SO4 concentration, hydrolysis temperature, and reaction time) that optimized the yield of tea stalk NCCs (TNCCs). Under the optimized operating conditions, the fundamental properties of TNCCs were characterized via transmission electron microscopy (TEM), X-ray diffraction (XRD), thermogravimetric analysis (TGA), laser diffraction particle-size analyzer, and scanning probe microscopy (SPM). Wood NCCs (WNCCs) and microcrystalline NCCs (MNCCs) were simultaneously prepared from common wood and microcrystalline cellulose under the same conditions. The results show that TNCCs not only shows similar physical and chemical properties with WNCCs and MNCCs, but also has better stability. Therefore, this study offers novel routes for high-valued utilization of tea stalk and provides some theoretical guidance for utilizing cellulose obtained from tea stalk.

Self-dispersing formulations for the delivery of poorly soluble drugs - Miscibility of phosphatidylcholines with oils and fats.

The presented study aimed to develop self-dispersing drug delivery systems based on natural phospholipids. A comprehensive investigation on miscibility was therefore carried out on mixtures containing one or two phosphatidylcholines as emulsifying excipients, ethanol 96% as co-solvent and different oils and fats. The soybean diacyl phosphatidylcholines Phospholipon90G and LipoidS75 as well as the monoacyl phosphatidylcholine LipoidSLPC80 were investigated for their maximum incorporation in the different lipids. Homogeneity and stability of the mixtures were determined according to their macroscopic appearance and by polarized light microscopy. Homogeneous formulations could be prepared with all three phosphatidylcholines in combination with medium chain triglycerides and semisolid hard fat. Phospholipon90G and LipoidS75 further yielded homogeneous formulations with rapeseed oil, soybean oil and diacetylated monoglycerides. Small- and wide-angle x-ray scattering studies indicated the presence of reverse micelles or (liquid) crystalline structures in the mixtures. Formulations with oils and Phospholipon90G or LipoidSLPC80 easily dispersed in Simulated Gastric Fluid making these mixtures suitable as self-dispersing formulations.

Mimicry of a biophysical pathway leads to diverse pollen-like surface patterns.

A ubiquitous structural feature in biological systems is texture in extracellular matrix that gains functions when hardened, for example, cell walls, insect scales, and diatom tests. Here, we develop patterned liquid crystal elastomer (LCE) particles by recapitulating the biophysical patterning mechanism that forms pollen grain surfaces. In pollen grains, a phase separation of extracellular material into a pattern of condensed and fluid-like phases induces undulations in the underlying elastic cell membrane to form patterns on the cell surface. In this work, LCE particles with variable surface patterns were created through a phase separation of liquid crystal oligomers (LCOs) droplet coupled to homeotropic anchoring at the droplet interface, analogously to the pollen grain wall formation. Specifically, nematically ordered polydisperse LCOs and isotropic organic solvent (dichloromethane) phase-separate at the surface of oil-in-water droplets, while, different LCO chain lengths segregate to different surface curvatures simultaneously. This phase separation, which creates a distortion in the director field, is in competition with homeotropic anchoring induced by sodium dodecyl sulfate (SDS). By tuning the polymer chemistry of the system, we are able to influence this separation process and tune the types of surface patterns in these pollen-like microparticles. Our study reveals that the energetically favorable biological mechanism can be leveraged to offer simple yet versatile approaches to synthesize microparticles for mechanosensing, tissue engineering, drug delivery, energy storage, and displays.

Potential application of novel liquid crystal nanoparticles of isostearyl glyceryl ether for transdermal delivery of 4-biphenyl acetic acid.

Novel liquid crystal nanoparticles (LCNs) composed of isostearyl glyceryl ether (GE-IS) and ethoxylated hydrogenated castor oil (HCO-60) were developed for the enhanced transdermal delivery of 4-biphenyl acetic acid (BAA). The physical properties and pharmaceutical properties of the LCNs were measured. The interaction between the intercellular lipid model of the stratum corneum and the LCNs was observed to elucidate the skin permeation mechanism. In the formulation, the LCNs form niosomes with mean particles sizes of 180-300 nm. The skin absorption mechanisms of LCNs are different, depending upon the application and buffer concentration. The LCNs composed of GE-IS and HCO-60 are attractive tools for use as transdermal drug delivery systems carriers for medicines and cosmetics, due to their high efficiency and safety.

Dual drug-loaded cubic liquid crystal gels for transdermal delivery: inner structure and percutaneous mechanism evaluations.

The goal of this paper was to develop and evaluate dual component-loaded with the hydrophilic sinomenine hydrochloride (SH) and lipophilic cinnamaldehyde (CA) cubic liquid crystal gels for transdermal delivery. The gels was prepared with a vortex method using phytantriol/water (70:30, w/w) and characterized by polarized light microscopy, small-angle X-ray scattering and rheology. The inner structure of the gels were Pn3m cubic phase and exhibited a pseudoplastic fluid behavior. Furthermore, the in vitro release profile showed that the release behavior of the two drugs from cubic liquid crystal gels conformed to Higuchi equation and were dominated by Fick's diffusion (n < 0.45). The ex vivo penetration experiment indicated that dual components-loaded liquid crystal gels can enhance and extend the skin permeation of these two drugs, especially the ratio of SH to CA is 1: 0.5. Finally, transdermal mechanisms were evaluated using laser scanning confocal microscopy and attenuated total reflectance-fourier transform infrared, hinting that hydrophilic and lipophilic drugs weaken each other's transdermal velocity at the initial stage of penetration. In short, the dual drug-loaded liquid crystal gels was a promising strategy for transdermal applications in treatment of chronic disease.

Cubic Liquid Crystalline Nanostructures Involving Catalase and Curcumin: BioSAXS Study and Catalase Peroxidatic Function after Cubosomal Nanoparticle Treatment of Differentiated SH-SY5Y Cells.

The development of nanomedicines for the treatment of neurodegenerative disorders demands innovative nanoarchitectures for combined loading of multiple neuroprotective compounds. We report dual-drug loaded monoolein-based liquid crystalline architectures designed for the encapsulation of a therapeutic protein and a small molecule antioxidant. Catalase (CAT) is chosen as a metalloprotein, which provides enzymatic defense against oxidative stress caused by reactive oxygen species (ROS) such as hydrogen peroxide (H2O2). Curcumin (CU), solubilized in fish oil, is co-encapsulated as a chosen drug with multiple therapeutic activities, which may favor neuro-regeneration. The prepared self-assembled biomolecular nanoarchitectures are characterized by biological synchrotron small-angle X-ray scattering (BioSAXS) at multiple compositions of the lipid/co-lipid/water phase diagram. Constant fractions of curcumin (an antioxidant) and a PEGylated agent (TPEG1000) are included with regard to the lipid fraction. Stable cubosome architectures are obtained for several ratios of the lipid ingredients monoolein (MO) and fish oil (FO). The impact of catalase on the structural organization of the cubosome nanocarriers is revealed by the variations of the cubic lattice parameters deduced by BioSAXS. The outcome of the cellular uptake of the dual drug-loaded nanocarriers is assessed by performing a bioassay of catalase peroxidatic activity in lysates of nanoparticle-treated differentiated SH-SY5Y human cells. The obtained results reveal the neuroprotective potential of the in vitro studied cubosomes in terms of enhanced peroxidatic activity of the catalase enzyme, which enables the inhibition of H2O2 accumulation in degenerating neuronal cells.

In situ hexagonal liquid crystal for intra-articular delivery of sinomenine hydrochloride.

The aim of this study was to investigate the release behaviors of sinomenine hydrochloride loaded via in situ hexagonal liquid crystal (ISH), and its potential to improve the local bioavailability in knee joints of sinomenine hydrochloride (SMH) after intra-articular administration. The ISH was prepared by a liquid precursor mixture containing phytantriol (PT), Vitamin E acetate (VEA), ethanol (ET), and water. The in vitro release profiles revealed a sustained release of SMH from the optimized ISH formula (PT/VEA/ET/water, 60.8:3.2:16.0:20.0, w/w/w/w), which was selected for the in vivo pharmacokinetics and preliminary pharmacodynamics studies. In both healthy and adjuvant-induced arthritis (AA) rats, the SMH loaded ISH showed significantly smaller SMH AUC0-∞ in plasma (P < 0.01), and higher SMH concentration in synoviums (2˜168 h) than that of SMH solution, indicating that the ISH significantly reduced the leakage of SMH into systemic circulation. The t1/2α of SMH loaded ISH in the knee joints of AA rats, was longer (13.42 h) than that of healthy rats (1.34 h) (P < 0.05), most likely that in vivo drug release behavior of SMH loaded ISH was affected by the physiological environment of the joint. It was found that the SMH loaded ISH could benefit AA-rats by suppressing the level of IL-1ß in comparison to SMH solutions. The results of the histopathology of knee joints in AA rats displayed that the SMH loaded ISH might be suitable for the development of treatment strategies for rheumatoid arthritis diseases.

Liquid crystalline assembly for potential combinatorial chemo-herbal drug delivery to lung cancer cells.

BACKGROUND: Lung cancer is the most common cancer and the leading cause of total deaths worldwide. Its classified into two major types including non-small cell lung carcinoma (NSCLC) and small cell lung carcinoma (SCLC) based on the origin of abnormal lung cells as well as the smoking status of the patient. NSCLC is the most common and aggressive type of lung cancer representing 80%-85% of all cases. PURPOSE: The aim of the study was to present lyotropic liquid crystalline nanoparticles (LCNPs) as promising carriers for co-delivery of the chemotherapeutic agent, pemetrexed (PMX) and the herbal drug, resveratrol (RSV) for effective lung cancer management. METHODS: The proposed PMX-RSV-LCNPs were prepared by hydrotrope method. Hydrophobic ion pairing with cetyl trimethyl ammonium bromide (CTAB) was implemented to increase the encapsulation efficiency of the hydrophilic PMX up to 95%±3.01%. RESULTS: The tailored PMX-RSV-LCNPs exhibited a particle size of 173±0.26 nm and biphasic release pattern with a relatively initial burst release within first 3-4 hour followed by sustained release up to 24 hours. Moreover, PMX-RSV-LCNPs manifested superior concentration and time dependent cytotoxicity profile against A549 lung cancer cells with IC50 4.0628 µg/mL. Besides, the enhanced cellular uptake profile based on bioadhesive properties of glyceryl monoolein (GMO) as well as energy independent (cholesterol dependent) pattern. In-vivo evaluations against urethane induced lung cancer bearing mice demonstrated the potentiality of PMX-RSV-LCNPs in tumor growth inhibition via inhibition of angiogenesis and induction of apoptosis. The results were supported by histopathological analysis and immunohistochemical Ki67 staining. Moreover, PMX-RSV-LCNPs displayed a promising safety profile via attenuating nephro- and hepatotoxicity. CONCLUSION: PMX-RSV-LCNPs elaborated in the current study hold a great promise for lung cancer treatment.

Understanding the kinetic mixing between liquid crystalline nanoparticles and agrochemical actives.

The use of liquid crystalline nanoparticles as potential agrochemical delivery agents or adjuvant systems is gaining traction due to the possibility that the systems can enhance penetration of the active and increase adhesion of the formulation to the leaf, increasing overall efficacy and decreasing the harmful environmental impact. However the interaction between liquid crystalline nanoparticles and active products is not well understood. Using small angle X-ray scattering we investigated the structural changes that occur to liquid crystalline nanoparticles upon addition of three common herbicides, 2,4-D 2-ethylhexyl ester, bromoxynil octanoate and haloxyfop-p-methyl ester active agrochemicals in the form of emulsions. It was found that the hydrophobic herbicides induced structural changes to varying degrees when pre-mixed with liquid crystalline forming lipids (phytantriol and glycerol monooleate) and also during dynamic mixing as emulsions.

Hierarchical spidroin micellar nanoparticles as the fundamental precursors of spider silks.

Many natural silks produced by spiders and insects are unique materials in their exceptional toughness and tensile strength, while being lightweight and biodegradable-properties that are currently unparalleled in synthetic materials. Myriad approaches have been attempted to prepare artificial silks from recombinant spider silk spidroins but have each failed to achieve the advantageous properties of the natural material. This is because of an incomplete understanding of the in vivo spidroin-to-fiber spinning process and, particularly, because of a lack of knowledge of the true morphological nature of spidroin nanostructures in the precursor dope solution and the mechanisms by which these nanostructures transform into micrometer-scale silk fibers. Herein we determine the physical form of the natural spidroin precursor nanostructures stored within spider glands that seed the formation of their silks and reveal the fundamental structural transformations that occur during the initial stages of extrusion en route to fiber formation. Using a combination of solution phase diffusion NMR and cryogenic transmission electron microscopy (cryo-TEM), we reveal direct evidence that the concentrated spidroin proteins are stored in the silk glands of black widow spiders as complex, hierarchical nanoassemblies (∼300 nm diameter) that are composed of micellar subdomains, substructures that themselves are engaged in the initial nanoscale transformations that occur in response to shear. We find that the established micelle theory of silk fiber precursor storage is incomplete and that the first steps toward liquid crystalline organization during silk spinning involve the fibrillization of nanoscale hierarchical micelle subdomains.

Curcumin-Loaded Liquid Crystalline Systems for Controlled Drug Release and Improved Treatment of Vulvovaginal Candidiasis.

Vulvovaginal candidiasis (VVC) is the most common infection caused by Candida albicans and greatly reduces the quality of life of women affected by it. Due to the ineffectiveness of conventional treatments, there is growing interest in research involving compounds of natural origin. One such compound is curcumin (CUR), which has been proven to be effective against this microorganism. However, some of CUR's physicochemical properties, especially its low aqueous solubility, make the therapeutic application of this compound difficult. Thus, the incorporation of CUR in mucoadhesive liquid crystalline systems (MLCSs) for vaginal administration may be an efficient strategy for the treatment of VVC. MLCSs are capable of potentiating the compound's action, releasing it in a controlled manner, and can enable longer exposure at the site of infection. In this study, MLCSs consisting of oleic acid and ergosterol 5:1 (w/w) as the oily phase, PPG-5-CETETH-20 as the surfactant, and a polymer dispersion of 1% chitosan as the aqueous phase, were developed for the application of CUR (MLCS-CUR) in VVC treatment. The formulations were characterized by polarized light microscopy (PLM), small-angle X-ray scattering (SAXS), oscillatory rheometry, continuous shear rheometry, texture profile analysis, and in vitro mucoadhesion. In addition, the antimicrobial activity was evaluated in vitro, and the effects on local fungal burden and cytokine profiles were investigated in a murine model of VVC. PLM and SAXS showed that the developed formulations presented a characteristic of a microemulsion. However, after the addition of artificial vaginal mucus (AVM), PLM showed that the formulations had structures similar to the "Maltese cross" characteristic of lamellar MLCS. Mucoadhesive test results showed an increase in the mucoadhesive strength of these formulations. Rheology analyses suggested long-lasting action of the formulation at the infected site. The in vitro antimicrobial activity assays suggested that CUR possesses antifungal activity against Candida albicans, determined after its incorporation into the MLCS. Further, MLCS-CUR was also more effective in vivo in the control of vaginal infection than treatment with fluconazole. Immunological assays showed that the ratio of pro-inflammatory (IL-1ß) to anti-inflammatory (TGF-ß) cytokines has decreased and that there is a reduction in the number of polymorphonuclear neutrophils recruited to the vaginal lumen, showing that treatment with MLCS-CUR was effective in modulating the inflammatory reaction associated with the infection. The results suggest that MLCSs could potentially be used in the treatment of VVC with CUR.

Improvement of cutaneous delivery of methylene blue by liquid crystals.

The purpose of this study was to evaluate the effect of composition and characteristics of liquid crystalline phases (LCPs) on cutaneous delivery of methylene blue (MB). LCPs were obtained by mixing Brij97® with water at various ratios; Brij97®:water at 8:2 (F8:2), 7:3 (F7:3), and 6:4 (F6:4) were selected, and MB was incorporated at 0.1%. F8:2 and F7:3 exhibited textures and small angle X-ray scattering (SAXS) patterns corresponding to lamellar phase, whereas F6:4 displayed characteristics of hexagonal phase. All three LCPs were stable for 9 months, and exhibited thixotropic pseudoplastic behaviour. Increasing water content increased viscosity. All three LCPs released less (3.2- to 6.6-fold) MB than control gel (3.0% hydroxyethylcellulose (HEC) + 0.1% MB), demonstrating their ability to sustain release. Despite the lower release, all LCPs improved skin retention of MB at 6 h post-application (1.3- to 2.1-fold) compared to the control gel. Among the LCPs, F8:2-mediated skin retention of MB was more pronounced, followed by F7:3. Consistent with the increased penetration, transepidermal water loss (TEWL) also increased after treatment with the LCPs (2.0-2.8 fold), which suggests their influence on skin barrier. Irritation studies by Hen's Egg Test - Chorioallantoic Membrane (HET-CAM) suggest that F7:3 and F6:4 may be better tolerated by the skin than F8:2.

Pharmacokinetic and Pharmacodynamics of Self-Assembled Cubic Liquid Crystalline Nanoparticle Gel After Transdermal Administration.

BACKGROUND The aim of this study was to assess the pharmacokinetics after transdermal administration by a novel skin microdialysis technology in rats. The guinea pig model was established by investigating the pharmacodynamics. MATERIAL AND METHODS Three different agents were given after hair removal, and the samples were extracted by microdialysis and detected by HPLC. Subcutaneous/plasma concentration-time curves of the 3 different agents were analyzed and the pharmacokinetic parameters were calculated. The SS-04B UV light therapy instrument was used in the modeling. Changes in melanin index and histopathology were observed with HE staining. RESULTS The increment and decrement results showed that the concentration had no significant effect on drug recovery both in vivo and in vitro. After the paeonol cubic liquid crystalline nanoparticles gel (PAE-LCNPs) was administered, the maximum peak time (tmax) of paeonol skin concentration appeared at 2.42±0.20 h, the maximum skin concentration Cmax was (926±105) ng/ml, and the area under the curve AUC0-8 was (8056±954) ng/h/ml. The tmax was shortened much more than in the other groups, and the performance of PAE-LCNPs targeting was good. Pharmacodynamic results showed that PAE-LCNPs can reduce melanocytes and reduce the melanin index, proving its utility in the treatment of melanin deposition. CONCLUSIONS The skin microdialysis study indicated PAE-LCNPs have good transdermal permeability and efficacy. Pharmacological experiments based on the study found that the topical pigmentation model of guinea pigs showed a better therapeutic effect.

In Vitro TyRP-1 Knockdown Based on siRNA Carried by Liquid Crystalline Nanodispersions: an Alternative Approach for Topical Treatment of Vitiligo.

PURPOSE: Vitiligo is a skin disease characterized by depigmentation and the presence of white patches that are associated with the loss of melanocytes. The most common explanation for the cause of this condition is that it is an autoimmune condition. TyRP-1 is involved in melanin pigment synthesis but can also function as a melanocyte differentiation antigen. This protein plays a role in the autoimmune destruction of melanocytes, which results in the depigmentation, characteristic of this disease. In this study, we evaluated liquid crystalline nanodispersions as non-viral vectors to deliver siRNA-TyRP-1 as an alternative for topical treatment of vitiligo. METHODS: Liquid crystalline nanodispersions were obtained and characterized with respect to their physical-chemical parameters including size, PdI and zeta potential, as well as Small Angle X-ray Scattering and complexing to siRNA. The effects of the liquid crystalline nanodispersions on the cellular viability, cell uptake and levels of the knockdown target TyRP-1 were evaluated in melan-A cells after 24 h of treatment. RESULTS: The liquid crystalline nanodispersions demonstrated adequate physical-chemical parameters including nanometer size and a PdI below 0.38. These systems promoted a high rate of cell uptake and an impressive TyRP-1 target knockdown (> 80%) associated with suitable loading of TyRp-1 siRNA. CONCLUSIONS: We demonstrated that the liquid crystalline nanodispersions showed promising alternative for the topical treatment of vitiligo due to their physical parameters and ability in knockdown the target protein involved with autoimmune destruction of melanocytes.