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In this study, a novel Bruton's tyrosine kinase inhibitor, ibrutinib, was loaded into chitosan/sulfobutylether-β-cyclodextrin nanoparticles (NPs). NPs have gained high loading efficiency for the hydrophobic drug due to the inclusion of cyclodextrin. Ibrutinib-loaded NPs with an average diameter of 277.9 nm and ζ-potential of +19.1 mV were obtained after regulating several influencing factors. Electrostatic reaction between mucin and NPs indicated that the NPs had a mucoadhesive property. Kinase catalytic phosphorylation was monitored by capillary zone electrophoresis and found that chitosan/sulfobutylether-β-cyclodextrin NPs did not weaken ibrutinib activity on the target kinase. In vitro drug release studies revealed that ibrutinib-loaded NPs exhibited a significantly slower gastric-release rate. This study applied a feasible nanocarrier for ibrutinib delivery, and the potential nanoformulation maintains drug activity and shows a sustained release property. These outcomes are helpful for the formulation exploitation of tyrosine kinase inhibitors. [ABSTRACT FROM AUTHOR]

[Display omitted] • The optimal LFT-MMs presented prominent enhancement in LFT solubility by 500-fold. • LFT-MMs remain stable for at least 1 month at 4 °C. • LFT-MMs rarely adsorbed proteins, and presented insignificant hemolytic rate. • LFT-MMs enhanced inhibitory activity against two main kinds of DTC cell lines. • The relative bioavailability compared with the original form of LFT was 176.7 %. The clinical efficacy of lenvatinib (LFT) is limited by its poor aqueous solubility and low bioavailability. In this work, LFT-loaded soy phospholipid and sodium glycocholate mixed micelles (LFT-MMs) were prepared through classical co-precipitation. And it was served as an oral administration to address these shortcomings. The preparation conditions were optimized by single-factor experiments. The mass ratio of PC, SGC and LFT, and the species of dispersing media were proved to be decisive factors in controlling the properties of LFT-MMs. The optimal LFT-MMs presented prominent enhancement (500-fold) in LFT solubility, high encapsulation efficiency (87.6 %) as well as suitable stability (>1 month at 4 °C). The biocompatibility of LFT-MMs was estimated by in vitro serum stability measurement and hemolysis test. It showed that serum proteins hardly adhered to the surface of LFT-MMs, and insignificant hemolytic rate (<0.5 %) was observed at the micelles concentration below 1 mg/mL. Cytotoxicity test (MTT assay) was carried out to judge the in vitro antitumor activity. LFT-MMs showed an enhanced inhibitory activity against two main kinds of differentiated thyroid cancer cells over LFT and LFT Mesylate. To estimate the in vivo oral bioavailability of LFT-MMs, SD rats were used as animal model. Notably, the relative bioavailability of LFT-MMs compared with the original form of LFT was 176.7 %. These superior characteristics indicated that the mixed micelles are promising water-soluble formulations suitable for LFT oral delivery. [ABSTRACT FROM AUTHOR]

Nanoscale metal–organic frameworks (NMOFs) have attracted considerable attention for controlled drug delivery. However, the interaction between nanoparticles and the biological macromolecules of physiological system must be valued because the formed protein corona will endow NMOFs with new biorecognition properties. In this study, we carried out detailed protein adsorption studies in vitro and cell uptake tests of HeLa cells for nanospherical Uio66 and nanooctahedral Uio67. Uio67 with higher binding constants to human serum albumin needed to combine more protein molecules to achieve colloidal stability state than that needed by Uio66, and this phenomenon led Uio67 to aggregate under the same incubation condition due to the formation of a single-layer protein. Uio67 also induced an evident conformation change in protein to stabilize the combination. In particular, the cell uptake efficiencies of the two systems showed a significant thickness dependence on the protein corona. When samples incubated in 10% fetal bovine serum (FBS), the intracellular rate was the highest for both systems, but the rate was not proportional to the FBS concentration. Results of this work are important to the development of the considerable potential NMOFs-based medicals and also provide additional insight into protein corona. Unlabelled Image • Distinct morphologies impacted on surface chemistry and cell uptake differently. • Cell uptake efficiencies showed thickness dependence on the protein corona. • Uio67 needed to combine more protein to achieve the colloidal stability state • HSA experienced different degrees conformation change to stabilize the combination. [ABSTRACT FROM AUTHOR]

This study aimed to develop a novel sustained release system for mesalazine (MSZ) by preparing hydroxypropyl-β-cyclodextrin (HP-β-CD) inclusion complex loaded chitosan (CS) nanoparticles (NPs). The HP-β-CD/MSZ complex was prepared at 1:1 stoichiometry and characterized by using various analysis techniques. The HP-β-CD/MSZ/CS NPs prepared under the optimum condition had a spherical shape (90±17 nm diameter), a narrow size distribution, and a high loading efficiency. Compared with free MSZ, the HP-β-CD/MSZ/CS NPs exhibited an obvious sustained release of MSZ. The activity of the NPs against a cytokine-triggered inflammatory response was evaluated in cytokine-stimulated HT-29 cell lines by monitoring key inflammatory mediators. The results revealed that compared with free MSZ, the NPs more strongly inhibited the production of NO, PGE 2 , and IL-8, indicating the NPs possibly had better anti-inflammatory effects. Therefore, the established HP-β-CD/MSZ/CS NPs may be a promising delivery system of MSZ. [ABSTRACT FROM AUTHOR]

This work aims to explore the inclusion mechanism and structure of cinnamaldehyde (CNMA) and cyclodextrins (CDs), and to provide some theoretical information for the application of CNMA and its inclusion. In this study, we prepared three kinds of inclusion and investigated the mechanism and structure by theory and experiment. Molecular docking and dynamical simulations presented a stable 1:1 inclusion complex and the visual structure model. The structural features indicated that the benzene ring of CNMA was enclosed in the hydrophobic cavity of CDs, which were consistent with the results of 1 H NMR, 2D-ROESY, Fourier transform infrared spectroscopy. The inclusion mechanism studies showed that the inclusion process was driven mainly by enthalpy with the binding constant following the order of DM (dimethyl) > HP (hydroxypropyl) > β-CD. Moreover, the inclusion complex showed an advantageous water solubility and dissolution rate compared with CNMA. [ABSTRACT FROM AUTHOR]

Lentinan is a natural β–glucan with various bioactivities and is combined with chemotherapy drugs for cancer treatment. Regorafenib is an oral multi-kinase inhibitor approved by FDA for treatment of metastatic colorectal cancer, advanced hepatocellular carcinoma, and metastatic gastrointestinal stromal tumors. Regorafenib has poor water solubility and multiple toxicities. We report drug–drug nanosuspensions of regorafenib and lentinan. Results of dynamic light scattering and scanning electron microscopy showed that the mean particle size of the regorafenib–lentinan nanosuspensions was approximately 200 nm and was uniformly distributed. Transmission electron microscopy findings indicated that lentinan stabilized the nanosuspensions by steric manner. Hydrogen bonds and hydrophobic interactions were found between regorafenib and lentinan by molecular dynamics simulation. The results of cytotoxicity assay and pharmacokinetics study in rats showed that the regorafenib–lentinan nanosuspensions reduced the toxicity and enhanced the in vitro anticancer activity and oral bioavailability of regorafenib. Lentinan as a natural stabilizer has the potential using for drug nanosuspensions. Drug–drug nanosuspensions are a new form of combination therapies that can reduce the number of drugs taken by patients and improve their compliance. • A drug–drug nanosuspension of regorafenib and lentinan was prepared. • The mechanism of lentinan as stabilizer was investigated. • Reduced hepatorenal cytotoxicity, enhanced anticancer activity of regorafenib. • The oral bioavailability of regorafenib was significantly improved. [ABSTRACT FROM AUTHOR]

Highlights • Molecular recognition between γ-lactone essences and human serum albumin were studied. • The morphology of HSA changed induced by interactions with ligands. • Ligands had weak binding with HSA, causing slight protein second structural changes. • Binding ability and secondary structure changes were positively correlated with side chain length. • Side chain length affected the binding by steric hindrance and hydrophobicity. Abstract The binding properties between γ-lactone essences and HSA were investigated to explore interactional mechanism and influence of ligand side chains on binding via computer simulations, microscopy, and multiple-spectroscopies. Docking and molecular dynamics presented protein recognition mode with low fluctuations. NMR analysis revealed that the lactone ring of ligands was the main group bound to HSA. UV–vis and lifetime results revealed that the combination was static quenching mechanism with binding constants of 102–103 L/mol. FTIR and CD spectra showed conformational changes in the protein secondary structure induced by ligands. Side chains affect the binding process through steric hindrance and hydrophobicity. AFM images showed the four compounds caused different effects on molecular size of HSA. In conclusion, the binding ability and the protein secondary structure changes had a positive correlation with the length of side chain. These studies are beneficial for understanding the safety and biological action of γ-lactone essences. [ABSTRACT FROM AUTHOR]

Tertiary butylhydroquinone (TBHQ) is a water-insoluble antioxidant. In this study, three cyclodextrin inclusion complexes were prepared to improve the water solubility of TBHQ and expand its range of application. Analysis of phase solubility indicated that TBHQ can form 1:1 inclusion complex with hydroxypropyl-beta-cyclodextrin (HP-β-CD) and dimethyl-beta-cyclodextrin (DM-β-CD) and 1:2 inclusion complex with beta-cyclodextrin (β-CD). The possible inclusion configuration between TBHQ and CDs was determined through FT-IR, PXRD, DSC, NMR, and SEM analyses. Results were validated by theoretical study of AutoDock molecular docking. The scavenging effects of the inclusion complexes were not effective on DPPH radical but higher on hydroxyl, superoxide and ABTS+ radicals than that of TBHQ monomer. Moreover, the water solubility of TBHQ increased after complexation with HP-β-CD and DM-β-CD. The stability of TBHQ is related to the type of storage materials used, and the stability can be improved by complexation with CDs. [ABSTRACT FROM AUTHOR]

In this study, a visible-light-driven photocatalyst Bi 2 WO 6 /TiO 2 composite was reported using one-step hydrothermal method and then coated on the polyester fabric. The samples were systematically characterized by X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), Brunauer-Emmett-Teller (BET) surface area, UV–vis diffuse reflection spectroscopy and photoluminescence spectroscopy (PL). The photocatalytic activity of Bi 2 WO 6 /TiO 2 coated polyester fabric was evaluated by degradation of Rhodamine B (RhB) and Methylene blue (MB) under visible light irradiation. The self-cleaning property of the fabrics was assessed through removing red wine stain. The results reveal that the Bi 2 WO 6 /TiO 2 composites with irregular shape are coated on the polyester fabric successfully. The UV–vis absorption spectra show a broad absorption band in the visible region, which extends the scope of absorption spectrum and helps to improve the photocatalytic degradation efficiency. Photocatalytic activities of the Bi 2 WO 6 /TiO 2 composite polyester fabric are associated with the content of TiO 2 . Bi 2 WO 6 /15%TiO 2 coated polyester fabric exhibits the degradation efficiency for RhB and MB up to 98% and 95.1%, respectively, which is much higher than that of pure Bi 2 WO 6 and TiO 2 coated polyester fabric. Moreover, Bi 2 WO 6 /15%TiO 2 coated polyester fabric shows good cycle stability toward continuous three cycles of photocatalytic experiment for dyes degradation. In addition, the Bi 2 WO 6 /TiO 2 coated polyester fabric shows good self-cleaning property. This work could be extended to design of other composite photocatalyst coating on the fabric for enhancing activity by coupling suitable wide and narrow band-gap semiconductors. [ABSTRACT FROM AUTHOR]

Thiabendazole (TBZ), which is oxidized into 5-hydroxythiabendazole (5-OH-TBZ) in vivo , is a commonly used food preservative. Interactions of TBZ and 5-OH-TBZ with human serum albumin (HSA) were comprehensively studied via multiple spectroscopic methods and molecular docking. This study focussed on the mechanistic and structural information on binding of TBZ and 5-OH-TBZ to HSA to evaluate the impact of the food additive on HSA. 1 H NMR spectra of the two ligands showed the binding exists. ITC and fluorescence spectroscopy results revealed that TBZ was a stronger ligand, with a binding constant of 10 5 l/mol and formed a more stable complex with HSA than did 5-OH-TBZ via electrostatic interaction. Spectroscopic results (UV–vis, FT-IR, and CD) showed that TBZ and 5-OH-TBZ caused conformational changes in HSA, in which α-helix and β-turn transformed into β-sheet, causing HSA structure to loosen. Docking programs showed that both TBZ and 5-OH-TBZ bound to HSA via IB. [ABSTRACT FROM AUTHOR]

Polybrominated diphenyl ethers (PBDEs) are persistent organic pollutants (POPs) that pose serious challenges to aquatic animals and environments. Compared with BDE-47 which was one of the most toxic congeners known to date, BDE-209 is less toxic with higher abundance in biotic and abiotic samples. In this study, we have explored the effects of BDE-47 and BDE-209 at different concentrations on the radical oxygen species (ROS) levels and the antioxidant defense system of Brachionus plicatilis. Antioxidant indexes were measured, including total protein content (TSP), the activities of antioxidant enzymes, lipid peroxidation and DNA damage. The results indicated that while low concentrations of PBDEs could activate the antioxidant defense mechanisms, prolonged exposure to higher concentrations of PBDEs could impair the antioxidative capacity of B.plicatilis (P < 0.05). The overwhelming of the B.plicatilis antioxidant defense mechanism led to an accumulation of free radicals, resulting in the overactivation of lipid peroxidation and the increased frequency of DNA damage (P < 0.05). By studying the toxicity of PBDEs and the detoxification mechanism of B.plicatilis , our research has revealed useful indexes for detecting and monitoring the level of BDE-47 and BDE-209 in the future. Altogether, this study holds immense value in the field of ecotoxicology and environmental safety and will aid in the proper management of PBDEs pollution. [Display omitted] • Minor PBDE exposure upregulates antioxidant activities and DNA repairs. • SeverePBDEexposurecausesantioxidative enzymedeficiency and releases radicals. • Excessive radicals inducelipid peroxidation and DNA damage. • PBDEs induce a cascade effect ofROS,TSP, antioxidative enzyme activity, lipid peroxidation and DNA integrity. • SOD, CAT and POD in rotifers are potential bioindicators of PBDE contamination. [ABSTRACT FROM AUTHOR]

• Different IBR formulations were prepared by mechanochemical methods. • MCC is an effective crystal growth inhibitor for the ternary IBR formulation. • The biosafety of the ternary formulation was the same as that of IBR. • The ternary IBR-OXA-MCC formulation enhances the oral bioavailability of IBR. The objective of present study is to explore whether polysaccharide could be a crystal growth inhibitor in poorly soluble antitumor drug Ibrutinib (IBR) formulation. In this work, small molecular ligands (amino or organic acids) in co-amorphous system (CAS) were preliminarily screened. A polysaccharide, microcrystalline cellulose (MCC) was selected to stabilize amorphous drug and enhance pharmacokinetic properties. Fourier-transform infrared, Raman, and X-ray photoelectron spectroscopy confirmed the ionic interaction of the ternary IBR formulation. Moreover, the biosafety of the ternary formulation was the same as that of IBR while the in vitro performance advantage of the ternary formulation was converted into higher bioavailability in vivo experiments. Overall, MCC as an effective crystal growth inhibitor in the novel ternary IBR formulation is a promising approach to improve the dissolution rate of crystalline drugs and the stability of amorphous drugs, as well as providing a theoretical basis for clinical applications. [ABSTRACT FROM AUTHOR]