Latest ArticlesThe transdermal drug delivery (TDD) shows considerable advantages over other administration pathways. However, conventional enhancing permeation methods face a series of challenges owing to barrier function provided by the skin, of which enhancing abilities either are so strong that it results in toxicity and irritation, or too weak to achieve desirable therapeutical effects. To address these issues, it is an urgent need to develop a novel method to overcome the limitations of current measures. Fortunately, in the preceding decades, ionic liquids (ILs) have been extensively studied and increasingly applied in pharmaceutical drug delivery due to their unique physicochemical and biological properties. What is more, tunability of structure resolves the challenges in processing active pharmaceutical ingredient (API) formulation, such as polymorphism and poor solubility of drugs. Thus, the presence of ILs provides an ample design space for the transdermal drug delivery system (TDDS). This review discusses the shortcomings of conventional enhancing permeation methods and introduces the application of ILs in transdermal delivery from three aspects: ⅰ) ILs are applied as enhancers to weaken the barrier function of the stratum corneum (SC). ⅱ) As counterions, ILs are combined with API to modify the physicochemical properties of drugs. ⅲ) ILs assist in the design of transdermal preparation for perfecting formulation. This review comprehensively introduces the major breakthroughs made in the applications of ILs, which can serve as guidance to provide novel ideas for formulation scientists who hit the bottleneck in the development of TDD.
Trauma and neurosurgery often result in dural defects and are followed by serious complications or even death, finding suitable dural replacement materials to repair the defective dura has important clinical significance. Porcine peritoneal acellular matrix (PPAM) is a promising alternative material, but its poor stability makes it difficult to meet the various needs of dural reconstruction. In this work, we developed a novel antibacterial cross-linking agent oxidized quaternized guar gum (OQGG) and used it for the first time to stabilize PPAM to construct a dural mater substitute (OQGG-PPAM). The results showed that 1.5% OQGG-PPAM presented suitable mechanical property as well as good thermal stability and resistance to enzymatic degradation. It also exhibited good antibacterial activity and good anti-leakage ability. Furthermore, 1.5% OQGG-PPAM not only exhibited excellent cell compatibility but also significantly stimulated the secretion of bFGF and VEGF from seeded cells which was convenient for dural remodeling. In vivo experiment, it also exhibited the excellent histocompatibility and good anti-adhesion property. This study showed that OQGG can be used as a novel antibacterial cross-linking reagent for crosslinking natural tissues and 1.5% OQGG-PPAM was a potential candidate material for dura mater substitute.
Rational design of electrode meterials with unique core-shell nanostructures is of great significance for improving the electrochemical performance of supercapacitors. In this work, we prepare several CuCo2O4@Ni-Co-S composite electrodes by a controllable hydrothermal and electrodeposition route. One-dimensional nanowires can shorten the ions transport path, while two-dimensional nanosheets expose many active sites. This enables three-dimensional structured composite with high electrochemical activity. The as-prepared heterostructured materials show a specific of 1048 C/g at 1 A/g. It still maintains 75.6% of initial capacity after 20000 cycles at 10 A/g. The device delivers an energy density of 79.2 Wh/kg when the power density reaches to 2280 W/kg. Moreover, it possesses an excellent mechanical stability after repeated folding at different angles
Cell stress responses are associated with numerous diseases including diabetes, neurodegenerative diseases, and cancer. Several events occur under cell stress, in which, are protein expression and organelle-specific pH fluctuation. To understand the lysosomal pH variation under cell stress, a novel NIR ratiometric pH-responsive fluorescent probe (BLT) with lysosomes localization capability was developed. The quinoline ring of BLT combined with hydrogen ion which triggered the rearrangement of π electrons conjugated at low pH medium, meanwhile, the absorption and fluorescent spectra of BLT showed a red-shifts, which gived a ratiometric signal. Moreover, the probe BLT with a suitable pKa value has the potential to discern changes in lysosomal pH, either induced by heat stress or oxidative stress or acetaminophen-induced (APAP) injury stress. Importantly, this ratiometric fluorescent probe innovatively tracks pH changes in lysosome in APAP-induced liver injury in live cells, mice, and zebrafish. The probe BLT as a novel fluorescent probe possesses important value for exploring lysosomal-associated physiological varieties of drug-induced hepatotoxicity.
The development of out-of-equilibrium self-assembly systems using light as input fuel is highly desirable and promising for the fabrication of smart supramolecular materials. Herein, we report the construction of new artificial light-fueled dissipative molecular and macroscopic self-assembly systems based on a visible-light-responsive transient quadruple H-bonding array, which consists of an azobenzene-modified ureidopyrimidinone (UPy) module (Azo-O-UPy) and a nonphotoactive diamidonaphthyridine (DAN) derived competitive binder (Napy-1). The visible light (410 nm) irradiation can induce the E to Z isomerization of the azobenzene unit of E-Azo-O-UPy to produce Z-Azo-O-UPy with an opened UPy binding site, which can complex with Napy-1 to form a quadruply H-bonded heterodimer. The heterodimer is metastable and can be quickly disassembled in dark, owing to the fast thermal relaxation of Z-Azo-O-UPy to E-Azo-O-UPy. While introducing such transient quadruple H-bonding interaction into a linear polymer system or a polymeric gel system, light-fueled out-of-equilibrium polymeric assembly both at molecular and macro-scale can be achieved.
Cancer is the leading cause that threatens human life expectancy due to the lack of effective therapies. Cancer immunotherapy has been explored to improve the body's immune system against cancer and accompanied by promising results in recent years. Interleukin 15 (IL-15), a pleiotropic immunomodulator, is critical for immune cells development and displays great anti-tumor potential in both preclinical and clinical trials. In this study, superagonist IL-15 plasmid (psIL-15) consisting of IL-15Rα-sushi-linker-IL-15 was constructed in order to secret superagonist IL-15 (sIL-15) in tumor site. A gene delivery system through self-assembly by methylated polyethylene glycol-b-polylactic acid-b-methylated polyethylene glycol (mPEG-PLA-mPEG) and 1, 2-dioleoyl-3-trimethylammonium-propane (DOTAP), named DMAM, was designed to deliver psIL-15. Further study showed that DMAM/psIL-15 could successfully deliver psIL-15 to tumor cells and the supernatants of the tumor cells could further stimulate lymphocytes proliferation as well as activation in vitro. Local delivery of DMAM/psIL-15 in animal models demonstrated significant tumor inhibition through enhancing immune cells responses, reducing angiogenesis, promoting tumor cell apoptosis and inhibiting proliferation, with no evidence of system toxicities. These results indicate that DMAM/psIL-15 may be a promising strategy for cancer immunotherapy.
In this work, a series of chiral phenethylamine synergistic tricarboxylic acid modified β-cyclodextrin bonded stationary phase for high performance liquid chromatography (HPLC) were synthesized via a simple one-pot synthesis approach. Various racemates (aryl alcohols, flavanones, triazoles, benzoin, etc.) were well separated on the tricarboxylic acid modified chiral stationary phases in both normal and reversed modes with good reproducibility and stability, and the influence of mobile phase composition on resolution (Rs) were deeply investigated. The RSD values of Rs for repeatability and column-to-column were below 1.28% and 3.05%, respectively. Hence, the fabrication of tricarboxylic acid modified chiral stationary phase (CSPs) is a new efficient strategy to improve the application of β-cyclodextrin as CSPs in the field of chromatography.
Berberine (BBR) is the primary alkaloid compound of the heat-clearing traditional Chinese medicine Huanglian (Coptis chinensis) and exerts regulatory effects on energy metabolism. However, the specific targets and molecular mechanisms are not clear. In this paper, the BBR-affected energy metabolism pathway was screened by nontargeted metabolomics, and a BBR-derived photoaffinity labeled (PAL) probe was designed to identify potential targets via a chemical proteomics approach. NDUFV1, a subunit of complex Ⅰ on mitochondria, was identified as a potential target of BBR. In the respiratory chain, BBR suppressed the activity of complex Ⅰ, reduced the electrochemical potential in the mitochondrial intermembrane and inhibited the generation of ATP and heat via competitive binding with NDUFV1. The results illustrated the underlying mechanism of BBR in the downregulation of energy metabolism.
The direct epoxidation of propylene by O2 is a significant and challenging topic. The key factor for this homogeneous aerobic epoxidation is the activation of molecular oxygen under mild conditions. In this work, the aerobic epoxidation of propylene catalyzed by manganese porphyrins was achieved in the presence of isoprene. Isoprene contains an allyl methyl group, and the α-H can be easily removed to achieve the activation of molecular oxygen. The conversion of propylene was 38% and the selectivity toward propylene oxide (PO) was up to 87%. The role of isoprene was demonstrated, and a plausible mechanism was proposed. The protocol reported herein is expected to provide a strategy for the simultaneous preparation of propylene oxide and isoprene monoxide.
The increasing pollution and human demand for a cleaner environment have made achieving the environmental sustainability a current research focus. As a "green" technology, semiconductor photocatalysis is of great significance to the environmental purification. Benefiting from the unique anisotropic crystal structure and electronic properties, layered photocatalytic nanomaterials show great potential for efficient photocatalytic environmental treatment. This review comprehensively summarizes the recent progress on layered photocatalytic nanomaterials for oxidation or reduction of pollutants in water and air along with the basic understanding of related mechanisms and developments in this field. First, the existing diversified layered photocatalysts are classified, and their different synthesis and modification strategies are discussed in detail to provide a comprehensive view of the material design that affects their photocatalytic performance. Subsequently, the extensive applications of the above-mentioned layered photocatalytic nanomaterials in environmental fields are systematically summarized, including photooxidation of water and air pollutants, and photoreduction of heavy metal pollutants, NO3-, BrO3- and CO2. Finally, based on the current research achievements in layered photocatalysts for environmental remediation, the future development direction and challenges are proposed.
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