Latest ArticlesStability of liposomes plays a crucial role in drug delivery, especially in oral aspect. The structural modification of liposomes has been the orientation of efforts to improve their stability and enable the controllability of payload release. This study reported a selenylation strategy to optimize the liposomal structure in an attempt to enhance the nanocarrier's stability, hence the bioavailability of emodin (EM), an active compound with poor water-solubility. EM-loaded selenized liposomes (EM-Se@LPs) were prepared by thin film dispersion followed by in situ reduction technique. The results showed that EM-Se@LPs were provided with enhancive gastrointestinal stability and exhibited sustained release of drug compared with EM-loaded liposomes (EM-LPs). However, the modified liposomes with Se depositing onto the interior and exterior bilayers did not substantially facilitate absorption of EM. The reinforced structure of liposomes irrelevant to absorption was affirmed to be due to good stability and absorbability of EM itself. Nevertheless, the present work provides an alternative option for stabilization of liposomes instead of conventional methods, which may be promising for oral delivery of physiologically unstable and/or poorly absorbed drugs and systemic drug delivery.
Plaque plays a central role in atherosclerosis (AS) progression, whereas inflammation and destruction of the plaque microenvironment contribute to plaque advancement. As a result, a therapy regime, which combines anti-inflammation and inhibition-degradation of plaque matrix, appears to be a promising strategy to combat AS. Herein, we report a pH-sensitive liposome co-loading with the anti-inflammatory agent (oridonin, ORD) and plaque-collagen protector (marimastat) for anti-AS therapy. ORD was first conjugated with hyaluronic acid (HA) to target the inflammation contributor, pro-inflammatory macrophages. Then, the conjugate assembled onto the MATT-loaded liposomes. The co-loaded system (~150 nm) significantly improved pharmacokinetics over the liposomes without anchoring the conjugate and accumulated effectively in the plaque. The preparation administration allowed efficient anti-AS activities in high-fat diet (HFD)-Apoe-/- mice by decreasing the pro-inflammatory cytokine expression in the serum, lessening the lesion area, alleviating the plaque collagen degradation, promoting macrophage polarization from phenotypic M1 to M2, reducing T helper (Th) 17 cells (Th17)/T regulatory cells (Tregs) and Th1/Th2 ratio, etc. Furthermore, the serum determination in AS patients demonstrated high expression of the inflammatory cytokines, indicating our finding may offer a potential guideline for clinical practice.
Pulmonary delivery is an effective drug delivery strategy for the treatment of local respiratory diseases. However, the rapid systemic absorption through the lung due to the thin barrier and persistent lung clearances influence the drug retention in the lung. In this study, we designed a lipid-coated genistein nanocrystals (Lipo-NCs) formulation to achieve enhanced efficiency of local pulmonary delivery. The Lipo-NCs were fabricated by modifying genistein nanocrystals (NCs) with phospholipid membrane through thin film hydration following the homogenization method. The prepared Lipo-NCs exhibited a decreased drug release rate compared with the naked NCs. Our results demonstrated that intracellular uptake and transcellular transport of NCs by the Calu-3 epithelial layer were reduced after lipid coating. Furthermore, the macrophages clearance was also impeded by this Lipo-NCs formulation. In vivo lung retention and distribution revealed that more genistein was retained in the lung after intratracheal administration of Lipo-NCs. The pharmacokinetic study displayed that the AUC(0-t) values of Lipo-NCs were 1.59-fold lesser than those of the NCs group, indicating a reduced systemic absorption. In conclusion, this research indicated that Lipo-NCs could be a suitable formulation for reducing systemic absorption and macrophages clearance, and thus enhancing drug concentration in lung by pulmonary delivery.
Reversal of regioselectivity in the catalytic asymmetric conjugate additions of 3-substituted oxindoles to β-nitroenones or β-nitroacrylates was established with chiral scandium catalysts. It enabled the construction of functionalized 3, 3-disubstituted oxindoles, including terminal and internal vinyl groups in excellent yields and ee values.
Polysubstituted pyrroles are very important scaffolds in many bioactive natural products and synthetic pharmaceuticals. Here, a new gold-catalyzed cycloaddition of alkynes with azadienes to access tetrasubstituted pyrroles is demonstrated. The neighboring hydroxylmethyl group serves a very important directing group through an addition/cycloaddition/elimination cascade. Diverse polysubstituted pyrroles were synthesized in good yields under mild conditions in one step, and tricyclic pyrrole containing heterocycles were easily obtained through derivatization.
Lithium-sulfur (Li-S) battery has been considered as one of the most promising next generation energy storage technologies for its overwhelming merits of high theoretical specific capacity (1673 mAh/g), high energy density (2500 Wh/kg), low cost, and environmentally friendliness of sulfur. However, critical drawbacks, including inherent low conductivity of sulfur and Li2S, large volume changes of sulfur cathodes, undesirable shuttling and sluggish redox kinetics of polysulfides, seriously deteriorate the energy density, cycle life and rate capability of Li-S battery, and thus limit its practical applications. Herein, we reviewed the recent developments addressing these problems through iron-based nanomaterials for effective synergistic immobilization as well as conversion reaction kinetics acceleration for polysulfides. The mechanist configurations between different iron-based nanomaterials and polysulfides for entrapment and conversion acceleration were summarized at first. Then we concluded the recent progresses on utilizing various iron-based nanomaterials in Li-S battery as sulfur hosts, separators and cathode interlayers. Finally, we discussed the challenges and perspectives for designing high sulfur loading cathode architectures along with outstanding chemisorption capability and catalytic activity.
Polyaniline-supported tungsten (W@PANI) was easily prepared by immersing polyaniline (PANI) in the aqueous solution of Na2WO4. It was found to be an efficient catalyst for oxidative deoximation reaction, the very important transformation for pharmaceutical industry. Besides the green features, the method employed very few of catalytic tungsten (0.048 mol% vs. oxime substrates), resulting in the high turnover numbers (TONs) of the catalyst (ca. 103 mol/mol) and the low metal residues in product (< 0.1 ppm). The reaction is applicable for a variety of substrates, including those containing heterocycles, which are key intermediates in medicine synthesis. It has also been successfully magnified to kilogram scale production to afford the desired carbonyl products smoothly.
The fabrication of highly effective photosensitizers has received considerable attention because of their attractive functions and applications in the fields of photodynamic therapy, photosynthesis, photocatalysis, etc. Thus, it is highly desirable to develop a new approach to enhance photosensitization efficiency. Herein, through coordination-driven self-assembly, a series of metallacycles with efficient fluorescence resonance energy transfer (FRET) were effectively constructed, which displayed higher photosensitization efficiency and photocatalytic activity than their model metallacycles without FRET due to broadband absorption and singlet energy transfer from the energy acceptor to the energy donor. Moreover, iodization of fluorophores induced a significant enhancement of the photosensitization efficiency and photocatalytic activity of the metallacycles. This research provides an efficient strategy for improving photosensitization efficiency and a promising platform for the preparation of effective photosensitizers and photocatalysts.
Although endogenous H2O2 is overexpressed in tumor tissue, the amount of endogenous H2O2 is still insufficient for chemodynamic therapy (CDT). In addition, the abundant cellular glutathione (GSH) could also consume •OH for reduced CDT. Thus, the elevation of H2O2 and the consumption of GSH in tumor tissue are essential for the increased •OH yield and amplified CDT efficacy. In this paper, host-guest interactions based supramolecular complexes self-assemblies (SCSAs) were fabricated by incorporating cinnamaldehyde (CA) and PEG-modified cyclodextrin host units (mPEG-CD-CA) with ferrocene-(phenylboronic acid pinacol ester) conjugates (Fc-BE) on the basis of CD-induced host-guest interactions. After being internalized by cancer cells, CA can be released from SCSAs through the pH-responsive acetal linkage, elevating the H2O2 level by activating NADPH oxidase. Then, Fc can catalyze the H2O2 to higher cytotoxic hydroxyl radicals (•OH). Moreover, quinone methide (QM) can be produced through H2O2-induced aryl boronic ester rearrangement and further consume the antioxidant GSH. In vitro and in vivo experiments demonstrate that SCSAs can be provided as potential amplified CDT nanoagents.
We found compound 12N-p-trifluoromethylbenzenesulfonyl matrinane (1) was a potent anti-diabetic agent. Thirty-five tricyclic matrinic derivatives were synthesized and determined for their stimulatory effects on glucose consumption in L6 myotubes, taking 1 as the lead. In high-fat diet (HFD) and STZ induced diabetic mice, 9a significantly lowers blood glucose, improves glucose tolerance, and especially alleviates diabetic nephropathy and islet damage. Mechanism study indicates that 9a simultaneously targets mitochondrial complex I to increase AMP/ATP ratio, as well as liver kinase B1 (LKB1) and calcium/calmodulin-dependent protein kinase (CaMKK), which synergistically activates AMPKα and then stimulates glucose transporter 4 (GLUT4) membrane translocation and 2-deoxyglucose (2-DG) uptake to exert anti-diabetic efficacy. Therefore, compound 9a with a novel structure is a promising anti-diabetic candidate with the advantage of multiple-target mechanism, worthy of further investigation.
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