ACS Nano
·
2022
·
IF 18.027
Xi Hu,Yu Sun,Xiaoqi Zhou,Bo Zhang,Hanxi Guan,Fan Xia,Shuangying Gui,Xueqian Kong,Fangyuan Li,Daishun Ling
The rigidity of polymeric micelles plays an important role in their biological behaviors. However, how drug loading affects the rigidity of polymeric micelles remains elusive. Herein, the indomethacin (IMC)-loaded Pluronic F127 micelle is used as a model system to illustrate the impact of drug loading on the rigidity and biological behaviors of polymeric micelles. Against expectations, micelles with moderate drug loading show higher cellular uptake and more severe cytotoxicity as compared to both high and low drug loading counterparts. Extensive one- and two-dimensional nuclear magnetic resonance (NMR) measurements are employed to reveal that the higher drug loading induces stronger interaction between IMC and hydrophilic block to boost the micellar rigidity; consequently, the moderate drug loading imparts micelles with appropriate rigidity for satisfactory cellular uptake and cytotoxicity. In summary, NMR spectroscopy is an important tool to gain insight into drug loading regulated micellar rigidity, which is helpful to understand their biological behaviors.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2022
·
IF 8.025
Jiankun Cao,Huayin Zhang,Qixun Nian,Qian Xu
Using electrospun chitosan/polyethylene oxide nanofibers mat (CS/PEO NFM) as carrier, Cu@CS/PEO NFM, a new tetracycline (TC) solid-state colorimetric sensor, were simply prepared by directly immobilizing Cu 2+ on surface of CS/PEO NFM. After immersing in TC solutions, Cu@CS/PEO NFM can display visible color changes to the naked eye within 5.0 min, and the TC concentration-dependent color changes can also be quantitatively analyzed with a smartphone. Because Cu 2+ can enhance the adsorption of CS/PEO NFM for TC, Cu@CS/PEO NFM possess a more sensitive response ability to TC, ensuring that the colorimetric sensing detection will not be interfered by other coexisting drugs. Due to the reversible combination of chitosan and Cu 2+ , the colorimetric sensing ability of Cu@CS/PEO NFM can be regenerated even after being reused at least 4 times. In addition, the naked eye detection limit of Cu@CS/PEO NFM-based colorimetric sensing is 65 μg kg −1 , which does not exceed the maximum residue limit in milk samples set by China (100 μg kg −1 ). The obtained results fully indicated the practical application value of this method in preventing the hazard of TC residues.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PLANTA MEDICA
·
2022
·Vol. 88
·期 13
·1190-1198
·
IF 3.007
Li-Juan Lang,Min Wang,Chang Lei,Yi Shen,Qi-Jie Zhu,Hong-Mei Diao,Hao Chen,Lei Shen,Xiang Dong,Bei Jiang,Chao-Jiang Xiao
Phloridzin is a lead compound of the prestigious antidiabetic gliflozins. The present study found that phloridzin highly accumulated in Malus rockii Rehder. The content of phloridzin in M. rockii was the highest among wild plants, with the percentage of 15.54% in the dry leaves. The structure of phloridzin was revised by proton exchange experiments and extensive 2D NMR spectra. Phloridzin exhibited significant hypolipidemic activity in golden Syrian hamsters maybe by increasing the expression of CYP7A1, at the doses of 50 mg/kg and 200 mg/kg. The total performance of anti-hyperlipidemic effect of phloridzin may be superior to that of lovastatin, though lovastatin was more active than phloridzin. In addition, phloridzin exhibited moderate antimalarial activity with inhibition ratio of 31.3 ± 10.9% at a dose of 25 mg/kg/day, and showed moderate analgesic activity with 28.0% inhibition at a dose of 50 mg/kg.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOCHEMICAL PHARMACOLOGY
·
2022
·
IF 6.1
Yanbei Tu,Lihua Tan,Tao Lu,Kai Wang,Haiyong Wang,Bing Han,Yuxin Zhao,Hanbin Chen,Yanfang Li,Haixia Chen,Meiwan Chen,Chengwei He
The roots of Glycine tabacina are used to treat rheumatoid arthritis (RA) and joint infection in folk medicine. Glytabastan B (GlyB), a newly reported coumestan isolated from this species, was found to significantly attenuate IL-1β-induced inflammation in SW982 human synovial cells at 3 and 6 μM, as evidenced by the decreased levels of pro-inflammatory mediators and matrix metalloproteinases (MMPs). GlyB also suppressed RANKL-induced osteoclastogenesis, decreased the expression of osteoclastogenic markers (NFATc1, CTSK , MMP-9) and osteoclast-mediated bone resorption. Further, GlyB administration (12.5 and 25 mg/kg) significantly inhibited inflammation, osteoclast formation and disease progression in collagen-induced arthritis (CIA) mice. Integration of network pharmacology , quantitative phosphoproteomic and experimental pharmacology results revealed that these beneficial actions were closely associated with the blockade of GlyB on the activation of MAPK , PI3K/AKT and their downstream signals including NF-κB and GSK3β/NFATc1. Drug affinity responsive target stability (DARTS) assay, cellular thermal shift (CETSA) assay and molecular docking analysis confirmed that there were direct interactions between GlyB and its target proteins ERK2 , JNK1 and class Ⅰ PI3K catalytic subunit p110 (α, β, δ and γ), which significantly contributed to the inhibition of activation of MAPK and PI3K/AKT pathways. In conclusion, these results strongly suggest GlyB is a promising multiple-target candidate for the development of agents for the prevention and treatment of RA.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2022
·
IF 16.744
Jiahui Chen,Minshan Guo,Runhui Fan,Yayun Peng,Ting Cai
Cocrystal engineering has become increasingly prevalent as an efficient and versatile route to overcome solubility limitations and improve the oral bioavailability of poorly soluble drugs. However, the unwanted solution-mediated phase transformation of cocrystals to less soluble parent drugs in the gastrointestinal tract may fail to deliver the drug in the body in a sufficient quantity. This study explores how bile salt sodium taurocholate (STC) affects the dissolution performance of indomethacin-saccharin (IMC-SAC) cocrystals. Fluorescence microscopy was used for in situ monitoring of the phase transformation of IMC-SAC cocrystals in the presence and absence of STC during dissolution. Intrinsic dissolution tests, atomic force microscopy and energy dispersive X-ray spectroscopy revealed that there was a significant relationship between the coformer release rate and the kinetics of the phase transformation of cocrystals. The addition of low-concentration STC in the buffer significantly inhibited the phase transformation of IMC-SAC cocrystals by retarding the release of SAC from cocrystals, leading to enhanced release rates of IMC. A molecular dynamics simulation revealed that preferential adsorption of STC molecules on the cocrystal surface may be responsible for the suppression of drastic release of SAC from the cocrystal lattice, thus preventing a rapid crystallization of IMC at the solid–liquid interface. The presence of STC in the buffer could also prolong the supersaturation of IMC, accounting for the overall improved in vitro and in vivo performance of IMC-SAC cocrystals. This study provides a deeper insight into the mechanisms of solution-mediated phase transformation of cocrystals in the presence of endogenous surfactant, which could also be used as an effective strategy to improve the absorption performance of pharmaceutical cocrystals by minimizing the risk of phase transformation during dissolution.
✓ 已验证
产品关联
DOI
高影响因子
Biomaterials Advances
·
2022
·
IF 0
Fenglei Zhang,Xuejing Pei,Xiaoxia Peng,Dongxia Gou,Xiao Fan,Xuefei Zheng,Chengcheng Song,Yifa Zhou,Sisi Cui
Pectin-based drug delivery systems hold great potential for oral insulin delivery, since they possess excellent gelling property, good mucoadhesion and high stability in the gastrointestinal (GI) tract. However, lack of enterocyte targeting ability and premature drug release in the upper GI tract of the susceptible ionic-crosslinked pectin matrices are two major problems to be solved. To address these issues, we developed folic acid (FA)-modified pectin nanoparticles (INS/DFAN) as insulin delivery vehicles by a dual-crosslinking method using calcium ions and adipic dihydrazide (ADH) as crosslinkers. In vitro studies indicated insulin release behaviors of INS/DFAN depended on COOH/ADH molar ratio in the dual-crosslinking process. INS/DFAN effectively prevented premature insulin release in simulated GI fluids compared to ionic-crosslinked nanoparticles (INS/FAN). At an optimized COOH/ADH molar ratio, INS/DFAN with FA graft ratio of 18.2% exhibited a relatively small particle size, high encapsulation efficiency and excellent stability. Cellular uptake of INS/DFAN was FA graft ratio dependent when it was at/below 18.2%. Uptake mechanism and intestinal distribution studies demonstrated the enhanced insulin transepithelial transport by INS/DFAN via FA carrier-mediated transport pathway. In vivo studies revealed that orally-administered INS/DFAN produced a significant reduction in blood glucose levels and further improved insulin bioavailability in type I diabetic rats compared to INS/FAN. Taken together, the combination of dual crosslinking and FA modification is an effective strategy to develop pectin nano-vehicles for enhanced oral insulin delivery.
✓ 已验证
产品关联
DOI
PubMed
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2022
·
IF 6.51
Yu Zou,Quan Zhou,Yinan Zhao,Defu Zhi,Huiying Chen,Rui Wang,Benzhi Ju,Shubiao Zhang
Ionizable lipids are the leading vectors for gene therapy. Understanding the effects of molecular structure on efficient gene delivery is one of the most important challenges for maximizing the utility of such lipid vectors. We synthesized an array of pH-responsive and ionizable lipids to investigate the relationship between lipid structure and activity. The optimized lipid (EDM) has double tertiary amines in the headgroup and an ester linker. EDM exhibited efficient DNA and siRNA delivery to, and gene silencing of, A549 cells. EDM has a p K a value of 6.67, which enabled it to quickly escape from the endosome after entering the cell; the ester linkages rapidly degraded and enabled gene release into the cytoplasm. EDM also delivered IGF-1R siRNA to inhibit tumor growth and induce cancer cell apoptosis by efficient inhibition of IGF-1R expression in mice. Our study on the structure–activity relationships of ionizable lipids will facilitate clinical applications.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING SCIENCE
·
2022
·
IF 4.889
Yuehua Deng,Wenhao Deng,Wenquan Huang,Zhiyong Zheng,Rui Zhang,Shiyuan Liu,Yanbin Jiang
Amorphization technology has been a promising strategy to improve the solubility and dissolution of drugs. This study aims to prepare norfloxacin (NFX) co-amorphous (CA) systems and evaluate the association between molecular descriptors and the formation and physical stability of NFX CAs. The molecular miscibility between NFX and 17 co-former candidates was firstly predicted using Hansen solubility parameters (HSPs) and six NFX CAs were successfully prepared by dry ball mill. Compared with crystalline NFX, four NFX CAs showed enhanced solubility (up to 2.50-fold) and dissolution rates. NFX CAs exhibited excellent physical stability under dry conditions. According to the quantitative calculations of Pearson correlation coefficient and Ridge regression, molecular descriptors have a great effect on NFX CA formation with structural parameters (Weight, VDW_vol, VDW_area, Rings) stronger than miscibility parameter Δ δ ¯ and p K a. These molecular descriptors corresponding to π···π interactions, molecular miscibility and ionic interactions are also responsible for physical stability. The results demonstrate that NFX CA can be stably formed if the co-former has more rings, smaller Δ δ ¯ (less than or close to 5 MPa 0.5 ) and larger Δp K a. This study offers a potential strategy to screen and design a CA system using multivariate data analysis based on theoretical considerations of molecular descriptors.
✓ 已验证
产品关联
DOI
高影响因子
SEPARATION AND PURIFICATION TECHNOLOGY
·
2022
·
IF 9.136
Yingfei Wang,Junhui Zhou,Fengliang Wang,Yi Xie,Shengwei Liu,Zhimin Ao,Chuanhao Li
Degrading organic pollutants while generating hydrogen from water splitting is an ideal application of photocatalysis. Herein, we presented an efficient photocatalyst, oxygen-doped crystalline carbon nitride, to power the degradation of various kinds of pharmaceuticals and personal care products and the simultaneous hydrogen production. The highest efficiency was achieved in treating the simulated wastewater containing naproxen (NPX), with the H 2 evolution rate of 819.1 µmol/g/h and the NPX degradation efficiency of 92 % upon visible light irradiation. Experimental and computational results suggested that the doped oxygen atoms thermodynamically favored the generation of hydroxyl peroxide for pollutant degradation and lowered the energy barrier of H 2 O reduction to produce hydrogen fuel. Most importantly, the catalysts functioned well in the natural aquatic environment including sea water, sewage water, river water, and well water. This study provides fundamental insights into photocatalytic water treatment with simultaneous hydrogen production, indicating an energy-recovering approach for wastewater treatment.
✓ 已验证
产品关联
DOI
高影响因子
WATER RESEARCH
·
2022
·
IF 13.4
Yue Liu,Hu Li,Ruigang Wang,Qian Hu,Ying Zhang,Zhanhui Wang,Jian Zhou,Guangzhou Qu,Tiecheng Wang,Hanzhong Jia,Lingyan Zhu
Indometacin (IDM), as a kind of non-steroidal anti-inflammatory drugs, has ecological and health risks, which is the potential precursor of chlorination disinfection byproducts (DBPs). Non-thermal discharge plasma was attempted to eliminate IDM and control subsequent DBPs formation. Satisfactory removal performance for IDM was realized by the plasma oxidation; almost 100% of IDM was removed within 2 min. Relatively greater removal efficiency was gained at a higher plasma voltage and a lower pH level. Electron paramagnetic resonance spectrometer revealed that reactive species ·OH, O 2 · − , and 1 O 2 were responsible for IDM decomposition. Based on analyses of Fourier transform infrared spectroscopy, two-dimensional correlation spectroscopy, three-dimensional fluorescence spectrum, and gas chromatography-mass spectrometer, attacks of reactive species resulted in sequence breakages in functional groups of IDM, leading to production of small molecular alcohols, acids, and amines. Possible decomposition pathways of IDM were proposed. The produced acetamide and 1H-indol-5-ol were important precursors of DBPs. Formation and toxicity of nitrogen-containing DBPs were dramatically inhibited after IDM degradation; however, those of haloacetic acids were strengthened. The relevant roadmaps among DBPs and degradation intermediates were figured out. This study revealed the underlying mechanisms of IDM degradation by discharge plasma and its potential risks in chlorination disinfection.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Food Bioscience
·
2022
·
IF 5.318
Fangwei Yang,Cheng Wang,Hang Yu,Yahui Guo,Yuliang Cheng,Weirong Yao,Yunfei Xie
The risk of the illegal addition of anti-inflammatory and analgesic chemical drugs in anti-rheumatic health foods should not be ignored. Market supervision and rapid on-site detection technology need to be strengthened. Thin-layer chromatography-surface-enhanced Raman spectroscopy (TLC-SERS), which has the advantages of simple operation, fast separation, and qualitative and quantitative detection, was used in this study. And these eleven chemical drugs (acetaminophen, acetylsalicylic acid, aminophenazone, dexamethasone , diclofenac sodium , hydrocortisone, indometacin, naproxen, phenylbutazone, piroxicam , prednisone 21-acetate) that may be added to anti-rheumatic health foods have been simultaneously identified by TLC-SERS combined with chemometrics method. The characteristic signals of the separated drug spots were collected by SERS, which were optimized by the gold colloidal nanoparticles' volume and integration time. Then SERS was subjected to principal component analysis (PCA) to reduce dimensionality and combined with the pattern recognition methods in chemometrics, such as PCA-Linear Discriminant Analysis (LDA), PCA-K Nearest Neighbor and PCA-Support Vector Machine, and eleven drug components were judged and identified. Moreover, the predictive performances of different models were also analyzed and compared. The results showed that the TLC plate and four organic solvents of petroleum ether, chloroform , ethyl acetate and acetic acid were selected as the developing agent. The dropping amount of gold colloidal nanoparticles and the integration time were set and optimized. The limit of detection of the simultaneous detection method of SERS was 10–100 mg/L. Furthermore, SERS was preprocessed by Gap-Segment 2nd Derivative, and then the PCA-LDA model was established, and the model's prediction accuracy can reach 100%. The method is simple, rapid, sensitive and accurate, and has low experimental instruments and equipment requirements. It is suitable for the on-site simultaneous detection of various anti-inflammatory and analgesic chemical drugs in health foods. It can also provide guarantee and support for the establishment of appropriate rapid detection methods and the development of supervision technology.
✓ 已验证
产品关联
DOI
高影响因子
Journal of Inflammation Research
·
2022
·
IF 4.631
Huixia Feng,Guilin Chen,Yongli Zhang,Mingquan Guo
Background Dysosma versipellis ( D. versipellis ) has been traditionally used as a folk medicine for ages. However, the specific phytochemicals responsible for their correlated anti-inflammatory, anti-proliferative and antiviral activities remain unknown. Purpose This study aimed to explore the specific active components in D. versipellis responsible for its potential anti-inflammatory, anti-proliferative, and antiviral effects, and further elucidate the corresponding mechanisms of action. Methods Bioaffinity ultrafiltration coupled to liquid chromatography–mass spectrometry (UF-LC/MS) was firstly hired to fast screen for the anti-inflammatory, anti-proliferative and antiviral compounds from rhizomes of D. versipellis , and then further validation was conducted using in vitro inhibition assays and molecular docking. Results A total of 12, 12, 9 and 12 phytochemicals with considerable affinities to Topo I, Topo II, COX-2 and ACE2 were fished out, respectively. The anti-proliferative assay in vitro indicated that podophyllotoxin and quercetin exhibited comparably strong inhibitory rates on A549 and HT-29 cells compared with 5-FU and etoposide. Meanwhile, kaempferol displayed prominent dose-dependent inhibition against COX-2 with IC 50 value at 0.36 ± 0.02 μM lower than indomethacin at 0.73 ± 0.07 μM. Furthermore, quercetin exerted stronger inhibitory effect against ACE2 with IC 50 value at 104.79 ± 8.26 μM comparable to quercetin 3- O -glucoside at 135.25 ± 6.54 μM. Conclusion We firstly showcased an experimental investigation on the correlations between bioactive phytochemicals of D. versipellis and their multiple drug targets reflecting its potential pharmacological activities, and further constructed a multi-target and multi-component network to decipher its empirical traditional applications. It could not only offer a reliable and valuable experimental basis to better comprehend the curative effects of D. versipellis but also provide more new insights and strategies for other traditional medicinal plants.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）