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The biocompatibility of metal-organic frameworks (MOFs) is necessary to humans but is far from being sufficiently addressed. This study focused on the effects of microsize on the biocompatibility of MOFs by selecting UiO67 with micron and submicron size as the MOFs models. Under the dose metric of surface area, the binding constant between UiO67 and human serum albumin (HSA) gradually increased with increased UiO67 size. Submicron UiO67 induced stronger conformational transformation and more greatly affected the protein surface hydrophobicity than micron UiO67. Micron UiO67 also inhibited the esterase-like activity of HSA through competitive inhibition mechanism, whereas submicron UiO67 inhibited it through noncompetitive inhibition mechanism. The size of UiO67 had little effect on hemocompatibility. A smaller size of UiO67, corresponded with a higher IC50 value for 293 T and LO2 cells, and the adsorption of HSA can effectively improve cytotoxicity. In vivo toxicity evaluations revealed that all UiO67 did not cause obvious distortion of organs, and they were metabolized primarily in the kidney. These results provided useful information about the toxicity of MOFs and experimental references for the development of MOFs-based engineering materials., (Copyright © 2022 Elsevier B.V. All rights reserved.)

With the development of the nuclear industry and clean energy, spent radioactive ion exchange resin has become a major concern that needs to be solved urgently. In this study, the mixed resin (sulfonic aid and quaternary ammonium polystyrene beads, 1:2, v/v) is co-pyrolyzed with manganese dioxide in a tube furnace, selecting argon as the reaction atmosphere. Manganese dioxide exhibits unique catalytic and oxidative activity, and a low mass remaining efficiency of 34.14% is obtained under low heating temperature of 300 ℃. The required decomposition temperatures of functional groups and benzene are decreased by approximately 100 ℃, and that of polymer chain is decreased by 130 ℃. The TGA analysis shows the decomposition temperature rule of functional groups and base polymer. The FT-IR spectra and XPS analysis reveal the bridging effects of manganese sulfonate and sulfide group. The SEM diagrams prove that the two processes including depolymerization and reunion could be found in co-pyrolysis. The XRD analysis indicates manganese dioxide undergoes the reduction path of MnO 2 →Mn 3 O 4 →MnO, and MnS is formed with the decomposition of manganese sulfonate. The possible mechanism of solid-phase reaction is proposed to explain the promotion of manganese dioxide on co-pyrolysis., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Ligand-receptor molecular recognitionis the basis of biological process. The Saturation Transfer Difference-NMR (STD-NMR) technique has been recently used to gain qualitative and quantitative information about physiological interactions at atomic-resolution. The molecular recognition patterns between Vitamin B12 (VB12) and human serum albumin (HSA) were investigated by STD-NMR supplemented by other spectroscopies and molecular docking. STD-NMR delivered a complete picture that the substituent groups on the tetrapyrrole ring of VB12 interacted with site III of HSA through binding epitope mapping and competitive probe experiments. STD-NMR and fluorescence results proved the moderate binding capability of VB12 and clarified a static, spontaneous, and temperature-sensitive binding mechanism. 3D-fluorencence, FT-IR and circular dichroism spectra showed a compact protein structure by interacting with VB12. Size distribution and surface hydrophobicity showed the surface properties changes of HSA caused by the binding of VB12. Computer simulation confirmed the recognition mode in theory and was compared with experiments. This work is beneficial for understanding the safety and biological action of VB12, and will attract researchers interested in NMR technology., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021. Published by Elsevier B.V.)

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., (Copyright © 2021. Published by Elsevier B.V.)

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., (Copyright © 2020 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)

Telaprevir (TVR) is typically a poorly soluble drug with an extremely low bioavailability of 1.7%. Polymorph modifications cannot improve the solubility of TVR because it only has a single unsolvated crystalline form. Co-crystals also provide limited bioavailability enhancement for TVR. Thus, in this study, we increased the solubility and dissolution rate of TVR through formulations of TVR-polymer solid dispersions. Three solid dispersions of TVR were successfully prepared by co-milling with polyvinylpyrrolidone K30 (PVP), polyethylene glycol 6000, and hydroxypropyl methylcellulose (HPMC), which were characterized by different techniques. According to X-ray powder diffraction and differential scanning calorimetry results, TVR presented in amorphous form in all solid dispersions. The fourier transform infrared spectra results indicated that TVR may connect with polymers through the N-H···O or O-H···O hydrogen bonds, which were verified by molecular docking. TVR-PVP and TVR-HPMC displayed a good stability at conventional RH levels, and their thermostabilities were better than those of milled TVR. Among the three solid dispersions, TVR-HPMC showed significant solubility and dissolution rate advantages in different media. Moreover, TVR-HPMC displayed the same anticancer efficacy with crystalline TVR and presented no toxic side effects to normal liver cells. Thus, TVR-HPMC showed potential application value., (Copyright © 2019 Elsevier B.V. All rights reserved.)

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., (Copyright © 2019. Published by Elsevier B.V.)

A novel hydrate (S H2O ) of nandrolone was prepared by anti-solvent methods. The crystallization processes with 2 schemes (A and B) were monitored by in-line near-infrared (NIR) spectroscopy. The amounts of S H2O in powder samples obtained by the anti-solvent crystallization and storage process were quantified by NIR combined with chemometrics methods. In-line NIR spectra from 4500 to 8000 cm -1 were chosen to capture physicochemical changes during the whole crystallization process. The combination of the principal component results with offline characterization (scanning electron microscopy, powder X-ray diffraction, NIR) data showed that both schemes yielded high purity S H2O products, but the crystallization speed of scheme B was significantly accelerated. It was demonstrated that in-line NIR spectroscopy combined with principal component analysis can be very useful to monitor in real time and control the anti-solvent crystallization process. Moreover, the solubility and the solid-state transformation of nandrolone under different storage conditions were investigated. The apparent solubility of S H2O was 2.19-2.44 times of Form I, and S H2O was relatively stable when stored at a high relative humidity and temperature below 25°C., (Copyright © 2018. Published by Elsevier Inc.)