Deep eutectic solvent self-assembled reverse nanomicelles for transdermal delivery of sparingly soluble drugs.

BACKGROUND: Transdermal delivery of sparingly soluble drugs is challenging due to their low solubility and poor permeability. Deep eutectic solvent (DES)/or ionic liquid (IL)-mediated nanocarriers are attracting increasing attention. However, most of them require the addition of auxiliary materials (such as surfactants or organic solvents) to maintain the stability of formulations, which may cause skin irritation and potential toxicity. RESULTS: We fabricated an amphiphilic DES using natural oxymatrine and lauric acid and constructed a novel self-assembled reverse nanomicelle system (DES-RM) based on the features of this DES. Synthesized DESs showed the broad liquid window and significantly solubilized a series of sparingly soluble drugs, and quantitative structure-activity relationship (QSAR) models with good prediction ability were further built. The experimental and molecular dynamics simulation elucidated that the self-assembly of DES-RM was adjusted by noncovalent intermolecular forces. Choosing triamcinolone acetonide (TA) as a model drug, the skin penetration studies revealed that DES-RM significantly enhanced TA penetration and retention in comparison with their corresponding DES and oil. Furthermore, in vivo animal experiments demonstrated that TA@DES-RM exhibited good anti-psoriasis therapeutic efficacy as well as biocompatibility. CONCLUSIONS: The present study offers innovative insights into the optimal design of micellar nanodelivery system based on DES combining experiments and computational simulations and provides a promising strategy for developing efficient transdermal delivery systems for sparingly soluble drugs.

Active pharmaceutical ingredient-ionic liquids assisted follicular co-delivery of ferulic acid and finasteride for enhancing targeted anti-alopecia.

Androgenetic alopecia (AGA) is the primary hair loss with impairing patients' quality of life. Finasteride (FIN) is an SRD5A2 inhibitor for AGA treatment, but oral FIN causes systemic adverse effects. Topical FIN delivery is anticipated to overcome this problem. Ferulic acid (FA) is a natural phenolic acid with vascular remodeling and anti-inflammatory effects. Herein, an active pharmaceutical ingredient ionic liquid (API IL) based on choline and FA (CF-IL) is for the first time constructed to load FIN for fabricating FIN CF-IL. CF-IL aims to act as carriers and cargos and enhance hair follicle (HF) co-delivery of FA and FIN for synergistic anti-alopecia. Thermal and spectroscopic analysis combined with quantum chemistry calculations and molecular dynamics confirm the formation of CF-IL. The CF-IL simultaneously increases the solubility of FA (∼648-fold) and FIN (∼686-fold), enhances the permeation and retention of FIN and FA through the follicular pathway, and promotes cellular uptake. FIN CFIL regulates the abnormal mRNA expressions in dihydrotestosterone-irritated hDPCs, and promotes hair regrowth in AGA mice in a combined manner with FIN and FA. These findings suggest that FA-based API IL is a promising approach for percutaneously co-delivering FA and FIN to HF, providing an enhanced targeting treatment for AGA.

Diagnostic performance of microRNA-29a in active pulmonary tuberculosis: a systematic review and meta-analysis.

BACKGROUND: In recent years, more and more studies have shown that microRNA-29a (miRNA-29a) can be used as a potential biomarker for active tuberculosis, but the results of these studies are not consistent. OBJECTIVE: To comprehensively evaluate the value of miRNA-29a in the diagnosis of active tuberculosis by meta-analysis. METHODS: The databases of CNKI, WanFang, PubMed, The Cochrane Library, Web of Science and EMBASE were searched for relevant studies. Studies were screened strictly according to inclusion and exclusion criteria. QUADAS-2 scale was used to evaluate the quality of the included studies. Data were extracted and analyzed by Meta-DiSc 1.4 and Stata 16.0 software. RESULTS: 13 articles were included, including a total of 1598 subjects, including 872 active tuberculosis patients and 726 controls. The combined sensitivity and specificity of miRNA-29a in the diagnosis of active tuberculosis were 78 % and 76 %, respectively, and the area under the overall summary receiver operating characteristic curve was 0.8564. CONCLUSION: miRNA-29a can be used as a biomarker for the diagnosis of active tuberculosis.

Tyrosine phosphorylation of band 3 impairs the storage quality of suspended red blood cells in the Tibetan high-altitude polycythemia population.

Due to environmental hypoxia on the Tibetan Plateau, local residents often exhibit a compensative increase in hemoglobin concentration to maintain the body's oxygen supply. However, increases in hemoglobin and hematocrit (Hct) pose a serious challenge to the quality of stored suspended red blood cells (SRBCs) prepared from the blood of high-hemoglobin populations, especially populations at high altitude with polycythemia in Tibet. To explore the difference in storage quality of SRBCs prepared from plateau residents with a high hemoglobin concentration, blood donors were recruited from Tibet (> 3600 m) and Chengdu (≈ 500 m) and divided into a high-altitude control (HAC) group, high-altitude polycythemia (HAPC) group and lowland control (LLC) group according to their hemoglobin concentration and altitude of residence. The extracellular acidification rate (ECAR), pyruvate kinase (PK) activity and band 3 tyrosine phosphorylation were analyzed on the day of blood collection. Then, whole-blood samples were processed into SRBCs, and storage quality parameters were analyzed aseptically on days 1, 14, 21 and 35 of storage. Overall, we found that tyrosine 21 phosphorylation activated glycolysis by releasing glycolytic enzymes from the cytosolic domain of band 3, thus increasing glucose consumption and lactate accumulation during storage, in the HAPC group. In addition, band 3 tyrosine phosphorylation impaired erythrocyte deformability, accompanied by the highest hemolysis rate in the HAPC group, during storage. We believe that these results will stimulate new ideas to further optimize current additive solutions for the high-hemoglobin population in Tibet and reveal new therapeutic targets for the treatment of HAPC populations.

Application value of self-management manual combined with case management superiority model in postoperative management of nasopharyngeal carcinoma after radiotherapy.

OBJECTIVE: To explore the application value of the self-management manual combined with the case management model in postoperative management of nasopharyngeal carcinoma after radiotherapy. METHODS: Eighty-four patients with nasopharyngeal carcinoma admitted to Yingtan People's Hospital from May 2020 to April 2022 were retrospectively included in this study. They were divided into the experimental group (receiving self-management manual combined with case management mode scheme, n=42) and the control group (receiving continuous management after conventional nasopharyngeal carcinoma radiotherapy, n=42) according to mode differences. The cancer-related fatigue [Cancer Fatigue Scale (CFS)], comfort status [General Comfort Questionnaire (GCQ)], self-management efficacy [Chinese Strategies Used by People to Promote Health (C-SUPPH)], self-care ability (self-care ability measurement), pain score [Visual analogue scale (VAS)], and quality of life [European Organization for Research and Treatment of Cancer QLQ-C30 (EORTC QLQ-C30)] were compared between the two groups after 4 weeks of radiotherapy. The adverse reactions of the two groups were recorded. Combined with periodic review and follow-up records, the prognostic factors of the two groups of patients were analyzed. RESULTS: After treatment, the scores of physical fatigue (12.83±1.10), emotional fatigue (9.78±1.32), cognitive fatigue (5.62±1.31), and total score of CFS (28.24±2.26) in the experimental group were 12.83±1.10. The control group physical fatigue (13.90±1.25) points, emotional fatigue (10.55±1.40) points, cognitive fatigue (6.80±1.75) points, and total CFS (31.33±2.59) points in both groups were lower than before treatment. The experimental group was lower than the control group (ALL P<0.05). The physiological, psychological, spiritual, socio-cultural, and environmental scores of the experimental group were higher than those of the control group (all P<0.05). The scores of health knowledge, self-care skills, self-care responsibility, and self-concept score of patients in the experimental group were higher than the control group (all P<0.05). After intervention, the VAS score of the experimental group was lower than that of the control group (P<0.05). After intervention, the EORTC QLQ-C30 score of both groups increased significantly as compared with pre-intervention. The score in the experimental group was significantly higher than that in the control group [(80.05±10.72) vs (68.11±12.10), P<0.05]. Postoperative (various) adverse reactions in the experimental group were lower than the control group (all P<0.05). The factors influencing the prognosis of nasopharyngeal carcinoma patients were age, tumor stage, and intervention mode by Cox model analysis (all P<0.05). CONCLUSION: The self-management manual combined with the case management mode can alleviate cancer fatigue, improve postoperative self-management ability, self-care ability, and quality of life of patients with nasopharyngeal cancer radiotherapy, reduce the occurrence of adverse reactions and improve the prognosis of patients. It is worth promoting in clinical settings.

Co-Delivery of Loxoprofen and Tofacitinib by Photothermal Microneedles for Rheumatoid Arthritis Treatment.

Rheumatoid arthritis (RA) is an autoimmune disease of synovial inflammation that affects populations worldwide. Transdermal drug delivery systems for treating RA have increased but remain challenging. We fabricated a dissolving microneedle (MN) system with photothermal (PT) polydopamine (PDA) to co-load the non-steroidal anti-inflammatory drug loxoprofen (Lox) and the Janus kinase inhibitor tofacitinib (Tof), with the aim of co-delivering Lox and Tof directly to the articular cavity, aided by the combination of MN and PT. In vitro and in vivo permeation studies showed that the PT MN significantly promoted drug permeation and retention in the skin. An in vivo visualization of the drug distribution in the articular cavity showed that the PT MN significantly promoted drug retention in the articular cavity. Importantly, compared to the intra-articular injection of Lox and Tof, the application of the PT MN to a carrageenan/kaolin-induced arthritis rat model exhibited superior performance in reducing joint swelling, muscle atrophy, and cartilage destruction. Furthermore, the PT MN downregulated the mRNA expression levels of proinflammatory cytokines, including TNF-α, IL-1ß, iNOS, JAK2, JAK3, and STAT3. The results show that the PT MN transdermal co-delivery of Lox and Tof is a new synergetic therapy with high compliance and good therapeutic efficacy for RA.

Oxymatrine-fatty acid deep eutectic solvents as novel penetration enhancers for transdermal drug delivery: Formation mechanism and enhancing effect.

Transdermal delivery of drugs is commonly limited by low skin permeability. The aim of the study was to synthesize deep eutectic solvents (DESs) based on oxymatrine (OMT) and fatty acids with various alkyl chain lengths (LCFAs) as novel vehicles, to solubilize the water-insoluble drug and enhance percutaneous penetration. Quercetin (QUE) was selected as a model drug. Combining differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR), and molecular simulations demonstrated that the formation of DESs was mediated by charge-assisted hydrogen bonding. Physicochemical properties including stability, viscosity, and solubilization capacity were also studied. Subsequently, the effect of three stable DESs on drug release and skin permeability was evaluated. The results showed that QUE was solubilized well and presented a different sustained release behavior in DESs. Meanwhile, DESs enhanced the skin permeation of OMT and QUE, which was influenced by alkyl chain lengths of LCFAs, whereas DES consisting of lauric acid (LA) exhibited the highest enhancing effect. FTIR, DSC, and molecular docking further demonstrated consistency between micro molecular mechanism and macro penetration behavior. Additionally, HaCaT cells treated with DESs showed high cell viability, suggesting their good skin safety. Taken together, OMT-LCFA DESs would be a promising penetration enhancer for transdermal drug delivery, which also provides guidance for the design of new DESs.

Combining the In Silico and In Vitro Assays to Identify Strobilanthes cusia Kuntze Bioactives against Penicillin-Resistant Streptococcus pneumoniae.

Leaves of Strobilanthes cusia Kuntze (S. cusia) are a widely used alexipharmic Traditional Chinese Medicine (TCM) in southern China for the prevention of cold and respiratory tract infectious diseases. One of the most common bacterial pathogens in the respiratory tract is the gram-positive bacterium Streptococcus pneumoniae. The antibiotic resistance of colonized S. pneumoniae makes it a more serious threat to public health. In this study, the leaves of S. cusia were found to perform antibacterial effects on the penicillin-resistant S. pneumoniae (PRSP). Confocal assay and Transmission Electron Microscopy (TEM) monitored the diminished cell wall integrity and capsule thickness of the PRSP with treatment. The following comparative proteomics analysis revealed that the glycometabolism-related pathways were enriched for the differentially expressed proteins between the samples with treatment and the control. To further delve into the specific single effective compound, the bio-active contents of leaves of S. cusia were analyzed by UPLC-UV-ESI-Q-TOF/MS, and 23 compounds were isolated for anti-PRSP screening. Among them, Tryptanthrin demonstrated the most promising effect, and it possibly inhibited the N-glycan degradation proteins, as suggested by reverse docking analysis in silico and further experimental verification by the surface plasmon resonance assay (SPR). Our study provided a research foundation for applications of the leaves of S. cusia as a TCM, and supplied a bio-active compound Tryptanthrin as a candidate drug skeleton for infectious diseases caused by the PRSP.

Diagnostic performance of microRNA-29a in active pulmonary tuberculosis: a systematic review and meta-analysis

Abstract Background: In recent years, more and more studies have shown that microRNA-29a (miRNA-29a) can be used as a potential biomarker for active tuberculosis, but the results of these studies are not consistent. Objective: To comprehensively evaluate the value of miRNA-29a in the diagnosis of active tuberculosis by meta-analysis. Methods: The databases of CNKI, WanFang, PubMed, The Cochrane Library, Web of Science and EMBASE were searched for relevant studies. Studies were screened strictly according to inclusion and exclusion criteria. QUA-DAS-2 scale was used to evaluate the quality of the included studies. Data were extracted and analyzed by Meta-DiSc 1.4 and Stata 16.0 software. Results: 13 articles were included, including a total of 1598 subjects, including 872 active tuberculosis patients and 726 controls. The combined sensitivity and specificity of miRNA-29a in the diagnosis of active tuberculosis were 78 % and 76 %, respectively, and the area under the overall summary receiver operating characteristic curve was 0.8564. Conclusion: miRNA-29a can be used as a biomarker for the diagnosis of active tuberculosis.

Spin-Decoupled Interference Metasurfaces for Complete Complex-Vectorial-Field Control and Five-Channel Imaging.

Light is a complex vectorial field characterized by its amplitude, phase, and polarization properties, which can be further represented by four basic parameters, that is, amplitudes and phases of two orthogonally polarized components. Controlling these parameters simultaneously and independently at will using metasurfaces are essential in arbitrarily manipulating the light propagation. However, most of the studies so far commonly require a great number of different meta-atoms or rely on diffraction under oblique incidence, which lack convenience and flexibility in design and implementation. Here, a new metasurface paradigm is proposed that can completely manipulate the amplitudes and phases of two spin components based on the interference effect, where only two different meta-atoms are applied. For proof-of-concept demonstration, two five-channel meta-holograms for imaging and information encryption are designed and experimentally characterized. The interference method provides a simple route toward compact complex and multifunctional meta-devices.

Chitosan/hyaluronan nanogels co-delivering methotrexate and 5-aminolevulinic acid: A combined chemo-photodynamic therapy for psoriasis.

Psoriasis does not respond adequately to the monotherapy, tailoring combined strategies for synergistical treatment remains challenging. We fabricated chitosan/hyaluronan nanogels to co-load methotrexate (MTX) and 5-aminoleavulinic acid (ALA), i.e., MTX-ALA NGs, for a combined chemo-photodynamic therapy for psoriasis. Compared with MTX-ALA suspension, the NGs enhanced the penetration and retention of MTX and ALA through and into the skin in vitro and in vivo (p < 0.001). NGs enhanced the cellular uptake (p < 0.001), protoporphyrin IX conversion (p < 0.001), and reactive oxygen species generation (3.93-fold), subsequently exerted the synergistical anti-proliferation and apoptosis on lipopolysaccharide-irritated HaCaT cells with the apoptosis rate of 78.6%. MTX-ALA NGs efficiently ameliorated the skin manifestations and down-regulated the proinflammatory cytokines of TNF-α and IL-17A in imiquimod-induced psoriatic mice (p < 0.001). Importantly, MTX-ALA NGs reduced the toxicities of oral MTX to the liver and kidney. The results support that MTX-ALA NG is a convenient, effective, and safe combined chemo-photodynamic strategy for psoriasis treatment.

Co-delivery of methotrexate and nicotinamide by cerosomes for topical psoriasis treatment with enhanced efficacy.

Psoriasis is an immune-mediated skin disorder that affects populations worldwide. Methotrexate (MTX) is a cytotoxic drug with powerful anti-proliferative and anti-inflammatory effects that has gained prominence in treating inflammatory diseases including psoriasis. However, low solubility and side effects through oral administration hinder its systemic application. In this study, we developed a novel niosomes based on ceramide (cerosomes) to co-deliver MTX and nicotinamide (NIC), i.e., MTX/NIC cerosomes, for topically treating psoriasis with the aim to enhancing the efficacy and reducing the toxicity. NIC significantly solublized MTX by forming hydrogen bonds with MTX. In vitro and in vivo permeation studies showed that the cerosomes significantly promoted drug permeation through and retention in the skin, and the enhancing mechanism was clarified by Fourier transform infraredand Raman spectroscopy. MTX/NIC cerosomes exhibited strong anti-proliferation effect on lipopolysaccharide- irritated HaCaT cells by arresting the cell cycle at S phase and inducing apoptosis. Importantly, compared to MTX oral administration, topical application of MTX/NIC cerosomes on imiquimod (IMQ)-induced psoriatic mouse model exhibited a superior performance in ameliorating skin lesions, reducing spleen index and epidermal thickness, and downregulating the mRNA expression levels of proinflammatory cytokines including TNFα, IL-23, IL-17A, IL-6, IL-1ß, and IL-22. Taken together, MTX/NIC cerosomes is a promising approach for psoriasis topical treatment.

Layered dissolving microneedles as a need-based delivery system to simultaneously alleviate skin and joint lesions in psoriatic arthritis.

Psoriatic arthritis (PsA) is a complicated psoriasis comorbidity with manifestations of psoriatic skin and arthritic joints, and tailoring specific treatment strategies for simultaneously delivering different drugs to different action sites in PsA remains challenging. We developed a need-based layered dissolving microneedle (MN) system loading immunosuppressant tacrolimus (TAC) and anti-inflammatory diclofenac (DIC) in different layers of MNs, i.e., TD-MN, which aims to specifically deliver TAC and DIC to skin and articular cavity, achieving simultaneous alleviation of psoriatic skin and arthritic joint lesions in PsA. In vitro and in vivo skin permeation demonstrated that the inter-layer retained TAC within the skin of ∼100 µm, while the tip-layer delivered DIC up to ∼300 µm into the articular cavity. TD-MN not only efficiently decreased the psoriasis area and severity index scores and recovered the thickened epidermis of imiquimod-induced psoriasis but also alleviated carrageenan/kaolin-induced arthritis even better than DIC injection through reducing joint swelling, muscle atrophy, and cartilage destruction. Importantly, TD-MN significantly inhibited the serum TNF-α and IL-17A in psoriatic and arthritic rats. The results support that this approach represents a promising alternative to multi-administration of different drugs for comorbidity, providing a convenient and effective strategy for meeting the requirements of PsA treatment.

Coupling Plasmonic System for Efficient Wavefront Control.

Efficient and flexible manipulation of electromagnetic waves using metasurfaces has attracted continuous attention in recent years. However, previous studies mainly apply sole resonance effect to accomplish the task. Here, we show that introducing a meta-coupling effect would reveal further physical insights in the electromagnetic wave control. To demonstrate this, a reflection-type coupling system composed by two identical linear resonances in a metal-insulator-metal configuration is theoretically proposed using the coupled-mode theory, whose phase diagram can be well controlled upon the coupling changes. Such intriguing optical property is verified by a double C-shaped resonator in the terahertz regime, where the coupling effect can be tuned by changing their either relative distance or rotation. More importantly, the reflection phase shift around the working frequency can be efficiently engineered without having to change the dimensions of the resonators. Two efficient anomalous metasurface deflectors are designed and experimentally characterized, whose maximum measured efficiency is more than 70%. The proposed controlling strategy further enriches the designing freedoms of metasurfaces and may find broad applications in realizing efficient and tunable functional devices.

Terahertz Spoof Surface Plasmonic Logic Gates.

Logic gates are important components in integrated photonic circuitry. Here, a series of logic gates to achieve fundamental logic operations based on linear interference in spoof surface plasmon polariton waveguides are demonstrated at terahertz frequencies. A metasurface-based plasmonic source is adopted to couple free-space terahertz radiation into surface waves, followed by a funnel-shaped metasurface to efficiently couple the surface waves to the waveguides built on a domino structure. A single Mach-Zehnder waveguide interferometer can work as logic gates for four logic functions: AND, NOT, OR, and XOR. By cascading two such interferometers, NAND and NOR operations can also be achieved. Experimental investigations are supported by numerical simulations, and good agreement is obtained. The logic gates have compact sizes and high intensity contrasts for the output "1" and "0" states. More complicated functions can be envisioned and will be of great value for future terahertz integrated computing.

Coherent Perfect Diffraction in Metagratings.

Metasurfaces are 2D engineered structures with subwavelength granularity, offering a wide range of opportunities to tailor the impinging wavefront. However, fundamental limitations on their efficiency in wave transformation, associated with their deeply subwavelength thickness, challenge their implementation in practical application scenarios. Here, it is shown how the coherent control of metagratings through multiple wave excitations can provide new opportunities to achieve highly reconfigurable broadband metasurfaces with large diffraction efficiency, beyond the limitations of conventional approaches. Remarkably, energy distribution between the 0th and higher diffraction orders can be continuously tuned by changing the relative phase difference between two excitation waves, enabling coherent control, with added benefits of enhanced efficiency and bandwidth. This concept is demonstrated for a thin electric metagrating operating at terahertz frequencies, showing that coherent control can overcome several of the limitations of single-layer ultrathin metastructures, and extend their feasibility in various practical scenarios.

Co-delivery of terbinafine hydrochloride and urea with an in situ film-forming system for nail targeting treatment.

Onychomycosis is a chronic nail disorder consisting of a fungal infection that causes physical and psychosocial discomfort to patients. However, its treatment remains challenging owing to the barrier of the highly keratinized nail plate and the short time that conventional formulations reside on nails. In this work, we developed an in situ film-forming system(IFFS) based on Eudragit® RLPO to co-deliver terbinafine hydrochloride (TBH) and urea, i.e., TBH-urea-RLPO IFFS, with the aim of overcoming the nail barrier, prolonging the residence time, and efficiently treating onychomycosis. The IFFS formulation formed a thin film with good appearance and adhesion upon application in situ. The physical states of TBH and urea in the film were evaluated with polarization microscopy and powder X-ray diffraction. TBH and urea were both amorphousmiscible components within the RLPO film. TBH release from TBH-urea-RLPO IFFS fitted to the Korsmeyer-Pappas model, and the cumulative release at 72 h was significantly higher than that from commercial preparations (Lamisil Pedisan® once). In vitro permeation of TBH from TBH-urea-RLPO IFFS through bovine hoof membranes was evaluated in comparison with the film containing TBH alone (TBH-RLPO) and commercial preparations. The retention and cumulative permeated amount of TBH were significantly enhanced for the TBH-urea-RLPO IFFS (170.80 ± 44.63 µg/cm2vs 75.49 ± 21.50 µg/cm2vs 60.25 ± 27.38 µg/cm2; 61.81 ± 16.09 µg/cm2vs 21.80 ± 11.56 µg/cm2vs 7.91 ± 1.03 µg/cm2, respectively), and the membranes treated with different formulations were observed with SEM and FTIR to identify the denaturing effect of urea on bovine hoof keratin. In vitro antifungal tests against Trichophyton rubrum,Microsporum canis, Fusarium, and Aspergillus fumigatus were cultured on Muller-Hinton agar; the findings indicated that TBH-urea-RLPO IFFS enhanced TBH antifungal activity. Overall, the results support that TBH-urea-RLPO IFFS is an efficient and promising approach for onychomycosis targeting treatment.

Integrating tacrolimus into eutectic oil-based microemulsion for atopic dermatitis: simultaneously enhancing percutaneous delivery and treatment efficacy with relieving side effects.

Background: Topical application of tacrolimus (FK506) was effective in treating atopic dermatitis (AD); however, the therapeutic efficiency is hampered by its poor penetration into the skin and local side effects of transient irritation symptoms with a burning sensation, a feeling of warmth or heat. Menthol and camphor have been widely used in topical compound formulations for adjunctive pharmacotherapy for antipruritics and analgesics owing to their cool nature, and both present skin penetration enhancing effects. Moreover, they can form a liquid eutectic oil to solubilize hydrophobic drugs. Purpose: Taking advantages of menthol/camphor eutectic (MCE), this work aims to integrate FK506 into MCE to construct a microemulsion system, i.e., FK506 MCE ME, which simultaneously enhances the percutaneous delivery and treatment efficacy, while reduces the side effects of FK506. Methods: The formulation of FK506 MCE ME was optimized and characterized. Different formulations containing FK506 were topically administered to treat 1-chloro-2, 4-dinitrobenzene (DNCB)-induced murine AD. Results: MCE solubilized FK506. FK506 in MCE ME penetrated skin in vitro more than in the commercial ointment, and MCE predominantly exerted the enhancing effects in MCE ME. FK506 MCE ME or FK506 MCE ME gel had greater effects on clinical symptoms, histological analysis, and IgE than did commercial FK506. The anti-pruritic and down-regulation of substance P effects of MCE ME vehicle mitigated the side effects of FK506 application. Conclusion: MCE ME presented the excellent properties of simultaneously enhancing the percutaneous delivery and treatment efficacy, while reducing the side effects of FK506 for AD. Therefore, MCE ME is a promising nanoscale system for FK506 to effectively treating AD with low irritation and high medication adherence. Chemical compounds studied in this article: Tacrolimus (PubChem CID: 445643); menthol (PubChem CID: 1254); camphor (PubChem CID: 2537).

Polarization-insensitive tunable terahertz polarization rotator.

A rotation-angle variable polarization rotator is proposed and demonstrated using an all-dielectric metasurface doublet. Such a transmissive device can conveniently rotate the polarization of incident light by any desired angles by mechanically changing the relative angle of the double metasurface layers regardless of the incident state of polarization. Under certain conditions the device acts as a full phase modulator for the circularly polarized incident wave. Hence, it has a promising application in polarization and phase control.