JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
·
2018
·
IF 2.831
Zifei Qin,Shishi Li,Zhihong Yao,Xiaodan Hong,Jinjin Xu,Pei Lin,Guoping Zhao,Frank J. Gonzalez,Xinsheng Yao
Corylin, an phenolic compound from Psoralea corylifolia , has been reported with various pharmacological properties but has poor bioavailability due to massive metabolism. In this study, twelve metabolites of corylin mainly involving in oxidation, hydration, glucuronidation and sulfation were detected in mice. Furthermore, the oxidation and hydration of corylin (M4) in human liver microsomes (HLM) and human intestine microsomes (HIM) were both efficient with high CL int (intrinsic clearance) values of 24.29 and 42.85 μL/min/mg, respectively. CYP1A1, 1B1 and 2C19 contributed most for M4 with the CL int values of 26.63, 33.09 and 132.41 μL/min/mg, respectively. Besides, M4 was strongly correlated with phenacetin- N -deacetylation ( r = 0.885, p = 0.0001) and tolbutamide-4-oxidation ( r = 0.727, p = 0.001) in twelve individual HLMs, respectively. In addition, corylin was efficiently glucuronidated (M7) in HLM (125.33 μL/min/mg) and in HIM (108.74 μL/min/mg). UGT1A1 contributed the most for M7 with the CL int value of 122.32 μL/min/mg. Meanwhile, M7 was significantly correlated with β-estradiol-3- O -glucuronidation ( r = 0.742, p = 0.006) in twelve individual HLMs. Moreover, the metabolism of corylin showed marked species differences. Taken together, corylin was subjected to massive first-pass metabolism in liver and intestine, while CYP1A1, 1B1, 2C19 and UGT1A1 were the main contributors. Finally, the proposed metabolic pathway of corylin involed CYP and UGT isoforms were summarized, which could help to understand the metabolic fate of corylin in vivo .
研究领域:
药理学
·
生物化学
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产品关联
DOI
PubMed
高影响因子
DRUG METABOLISM AND DISPOSITION
·
2024
·Vol. 52
·期 2
·106-117
·
IF 4.4
Yufan Zhou,Hongjiao Dong,Jiang Fan,Mingshe Zhu,Lu Liu,Yongbin Wang,Pingming Tang,Xiaoyan Chen
Ciprofol (HSK3486) is a novel intravenous agent for general anesthesia. In humans, HSK3486 mainly undergoes glucuronidation to form M4 [fraction of clearance (fCL): 62.6%], followed by the formation of monohydroxylated metabolites that further undergo glucuronidation and sulfation to produce M5-1, M5-2, M5-3, and M3 (summed fCL: 35.2%). However, the complete metabolic pathways of HSK3486 in humans remain unclear. In this study, by comparison with chemically synthesized reference standards, three monohydroxylated metabolites [M7-1, 4-hydroxylation with an unbound intrinsic clearance (CLint,u) of 2211 μl/min/mg; M7-2, ω-hydroxylation with a CLint,u of 600 μl/min/mg; and M7-3, (ω-1)-hydroxylation with a CLint,u of 78.4 μl/min/mg] were identified in human liver microsomes, and CYP2B6 primarily catalyzed their formation. In humans, M7-1 was shown to undergo glucuronidation at the 4-position and 1-position by multiple UDP-glucuronosyltransferases (UGTs) to produce M5-1 and M5-3, respectively, or was metabolized to M3 by cytosolic sulfotransferases. M7-2 was glucuronidated at the ω position by UGT1A9, 2B4, and 2B7 to form M5-2. UGT1A9 predominantly catalyzed the glucuronidation of HSK3486 (M4). The CLint,u values for M4 formation in human liver and kidney microsomes were 1028 and 3407 μl/min/mg, respectively. In vitro to in vivo extrapolation analysis suggested that renal glucuronidation contributed approximately 31.4% of the combined clearance. In addition to HSK3486 glucuronidation (M4), 4-hydroxylation (M7-1) was identified as another crucial oxidative metabolic pathway (fCL: 34.5%). Further attention should be paid to the impact of CYP2B6- and UGT1A9-mediated drug interactions and gene polymorphisms on the exposure and efficacy of HSK3486.
研究领域:
药理学
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生物化学
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临床医学
✓ 已验证
DOI
PubMed
高影响因子
TALANTA
·
2016
·
IF 4.035
Jingwen Lan,Jinyang Chen,Ningxing Li,Xinghu Ji,Mingxia Yu,Zhike He
Fluorescent magnetic multifunctional microparticles were fabricated by a facile droplet microfluidic strategy. Two sodium alginate streams, one doped with Fe 3 O 4 nanoparticles (NPs) and the other with CdSe/ZnS quantum dots , were introduced into a flow-focusing channel as a type of parallel laminar flow to form droplets containing two distinct parts. Then, at the serpentine channel, the Ca 2+ in the oil phase diffused into the droplets, causing the solidification of the droplets. Thus, the Janus microparticles with excellent magnetic/fluorescent properties formed. The flow conditions were optimized and the effects of the flow rates on magnetic/fluorescent compositions were carefully investigated. Luminescent labeling and magnetic separation were simultaneously realized with the newly designed microparticles. Moreover, spatial separation between Fe 3 O 4 NPs and QDs prevented the interference of QDs photoluminescence by the magnetic particles. The as-prepared fluorescent magnetic Janus particles were also successfully employed for DNA assay, which demonstrated the potential of the multifunctional microbeads in biological applications.
研究领域:
生物医学工程
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材料科学
·
分析化学
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产品关联
DOI
PubMed
高影响因子
Biomicrofluidics
·
2013
·Vol. 7
·期 4
·
IF 3.385
Liu Zhou,Shum Ho Cheung
In this work, we demonstrate a robust and reliable approach to fabricate multi-compartment particles for cell co-culture studies. By taking advantage of the laminar flow within our microfluidic nozzle, multiple parallel streams of liquids flow towards the nozzle without significant mixing. Afterwards, the multiple parallel streams merge into a single stream, which is sprayed into air, forming monodisperse droplets under an electric field with a high field strength. The resultant multi-compartment droplets are subsequently cross-linked in a calcium chloride solution to form calcium alginate micro-particles with multiple compartments. Each compartment of the particles can be used for encapsulating different types of cells or biological cell factors. These hydrogel particles with cross-linked alginate chains show similarity in the physical and mechanical environment as the extracellular matrix of biological cells. Thus, the multi-compartment particles provide a promising platform for cell studies and co-culture of different cells. In our study, cells are encapsulated in the multi-compartment particles and the viability of cells is quantified using a fluorescence microscope after the cells are stained for a live/dead assay. The high cell viability after encapsulation indicates the cytocompatibility and feasibility of our technique. Our multi-compartment particles have great potential as a platform for studying cell-cell interactions as well as interactions of cells with extracellular factors.
研究领域:
生物工程
·
细胞生物学
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产品关联
DOI
PubMed
高影响因子
LANGMUIR
·
2021
·
IF 3.882
Haohong Sun,Shaohui Lin,Flora T. T. Ng,Sushanta K. Mitra,Qinmin Pan
Anisotropic microparticles have plenty of applications for their asymmetric structure and precisely modified surface. In our research, the uniform anisotropic microparticles with benzyl chloride group were synthesized successfully via emulsion interfacial polymerization. By varying the degree of cross-linking and the concentration of slightly hydrophilic monomer 4-vinyl benzyl chloride (VBC), several types of microparticles with different concavities and different shapes of microparticles (hemisphere, bowl-like, egg-like, etc.) were obtained. Nanoporous microparticles with a walnut-like heterostructure were achieved with modified hydrophilic seeds with the same strategy. The potential applications of shape-controllable fluorescent microparticles and surface modification of microparticles by thiol-click reaction were explored. The modified microparticles achieved in this study are very useful in labeling, tracing, protein separation, and other biomedical fields.
研究领域:
材料科学
·
生物医学工程
✓ 已验证
DOI
高影响因子
POLYMER BULLETIN
·
2021
·Vol. 79
·期 4
·2173-2188
·
IF 2.87
Hou Jiazi,Zhou Guibin,Hu Jinlun,Wang Yihuan,Gao Shuang
Microparticles had attracted a lot of attention for biomedical applications because of their injectable and biomimetic properties. We reported a method for preparing Polylactic acid (PLA)/Polyvinylpyrrolidone (PVP) core–shell microparticles by single capillary electrospraying and explored their potential applications for drug-loading. The shape of microparticles can be controlled by varying ratios of PLA and PVP during the electrospraying process. Different morphologies were achieved including spindle-like, erythrocyte-like and disk-like microparticles. Furthermore, the method of preparing core–shell microparticles was simple and repeatable. Compared with spherical microparticles, erythrocyte-like microparticles can flow through capillaries by morphing into a parachute-like shape. When the particle morphology converted to disk-like, the increase of water contact angle attributed to the PVP rapid dissolution and the residual PLA interconnection to form a continuous hydrophobic membrane. Besides, the microparticle membrane was extremely low-toxic to cells by MTT assay. Taken together, we prepared injected core–shell microparticles by single capillary electrospraying, which had potential application in drug-loading.
研究领域:
生物医学工程
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材料科学
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药剂学
✓ 已验证
DOI
高影响因子
RSC Advances
·
2018
·Vol. 8
·期 72
·41368-41375
·
IF 2.936
Liangliang He,Jinjin Xu,Qi Wang,Yezi Zhang,Zifei Qin,Yang Yu,Zhengming Qian,Zhihong Yao,Xinsheng Yao
Shogaols, mainly [6]-shogaol (6S), [8]-shogaol (8S) and [10]-shogaol (10S), the predominant and characteristic pungent phytochemicals in ginger, are responsible for most of its beneficial effects. However, poor oral bioavailability owing to extensive glucuronidation limits their application. The present study aimed to characterize the glucuronidation pathways of 6S, 8S and 10S by using pooled human liver microsomes (HLM), human intestine microsomes (HIM) and recombinant human UDP-glucosyltransferases (UGTs). The rates of glucuronidation were determined by incubating shogaols with uridine diphosphate glucuronic acid-supplemented microsomes. Kinetic parameters were derived by appropriate model fitting. Reaction phenotyping assays, activity correlation analyses and relative activity factors were performed to identify the main UGT isoforms. As a result, one mono-4′-O-glucuronide was detected after incubating each shogaol with HLM and HIM. Enzymes kinetic analysis demonstrated that glucuronidation of shogaols consistently displayed the substrate inhibition profile, and the liver showed higher metabolic activity for shogaols (CLint = 1.37–2.87 mL min−1 mg−1) than the intestine (CLint = 0.67–0.85 mL min−1 mg−1). Besides, reaction phenotyping assays revealed that UGT2B7 displayed the highest catalytic ability (CLint = 0.47–1.17 mL min−1 mg−1) among all tested UGTs. In addition, glucuronidation of shogaols was strongly correlated with AZT glucuronidation (r = 0.886, 0.803 and 0.871 for glucuronidation of 6S, 8S and 10S, respectively; p < 0.01) in a bank of individual HLMs (n = 9). Furthermore, UGT2B7 contributed to 40.8%, 34.2% and 36.0% for the glucuronidation of 6S, 8S and 10S in HLM, respectively. Taken altogether, shogaols were efficiently metabolized through the glucuronidation pathway, and UGT2B7 was the main contributor to their glucuronidation.
研究领域:
药理学
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生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
XENOBIOTICA
·
2018
·
IF 1.857
Li Wang,Xiaodan Hong,Zhihong Yao,Yi Dai,Guoping Zhao,Zifei Qin,Baojian Wu,Frank J. Gonzalez,Xinsheng Yao
1. Icaritin is a natural flavonoid with anti-osteoporosis activity. This study aimed to characterize icaritin glucuronidation by pooled human liver microsomes (HLM) and pooled human intestine microsomes (HIM), and to determine the contribution of individual UDP-glucuronosyltrans-ferase (UGT) enzyme to icaritin glucuronidation.2. Glucuronidation rates were determined by incubating icaritin with uridine diphosphate glucuronic acid (UDPGA)-supplemented microsomes. Kinetic parameters were derived by appropriate model fitting. Relative activity factors and activity correlation analysis were performed to identify main UGT isoforms.3. UGT1A3, 1A7, 1A8, 1A9 and 2B7 were mainly responsible for catalyzing the formation of two glucuronides (G1 and G2). Icaritin 3-O-glucuronidation (G1) was significantly correlated with Chenodeoxycholic acid (CDCA) glucuronidation (r = 0.787, p = 0.002), propofol glucuronidation (r = 0.661, p = 0.019) and Zidovudine (AZT) glucuronidation (r = 0.805, p = 0.002). Similarly, icaritin 7-O-glucuronidation (G2) was also correlated with CDCA glucuronidation (r = 0.640, p = 0.025), propofol glucuronidation (r = 0.592, p = 0.043) and AZT glucuronidation (r = 0.661, p = 0.019). In addition, UGT1A3, 1A9 and 2B7 contributed 37.5, 33.8 and 21.3% for G1 in pooled HLM, respectively. Also, UGT1A3, 1A9 and 2B7 contributed 34.3, 20.0 and 8.6% for G2 in pooled HLM, respectively.4. Icaritin was subjected to significant glucuronidation, wherein UGT1A3, 1A7, 1A8, 1A9 and 2B7 were main contributing enzymes.
研究领域:
药理学
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生物化学
·
药物代谢
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CERAMICS INTERNATIONAL
·
2022
·
IF 5.532
Chenchen Zhou,Jia Man,Jianyong Li,Bin Qi,Zesheng Hua,Chenxu Liu,Minyi Zhang,Jianfeng Li
Anisotropic ceramic microparticles have been extensively studied in various fields such as mechanical transmission, wave absorbing, structural materials, and abrasives owing to their remarkable properties. The shape of the microparticles plays an important role in their functions. Here, we presented a facile and tunable microfluidic approach to fabricate the ceramic microparticles (∼370 μm in diameter) with the bowl shape, which have been quite challenging for synthesizing to date. Double UV lights were applied to shape the microparticles. By tailoring the cross angle and the intensities of both UV lights, bowl-shaped ceramic microparticles with different opening sizes (0–340 μm) and hollow spherical ceramic microparticles with different-sized through-holes ( f = 0–0.265) were fabricated. These obtained ceramic microparticles hold great potentials to be used as the micro-components in sewage filters, micro ball valves, MEMS , micro-robots, and so forth.
研究领域:
材料科学
·
微流控技术
·
纳米技术
·
机械工程
·
环境工程
✓ 已验证
产品关联
DOI
高影响因子
Frontiers in Pharmacology
·
2023
·
IF 5.6
Jia Xu,Quan Zhou,Pengjiao Hou,Yu Wang,Peiwu Geng,Zebei Lu,Yunfang Zhou,Dapeng Dai,Shuanghu Wang
Macitentan was approved by the United States Food and Drug Administration (FDA) in 2013 for the treatment of pulmonary arterial hypertension (PAH). Bergapten is a furanocoumarin that is abundant in Umbelliferae and Rutaceae plants and is widely used in many Chinese medicine prescriptions. Considering the possible combination of these two compounds, this study is aimed to investigate the effects of bergapten on the pharmacokinetics of macitentan both in vitro and in vivo . Rat liver microsomes (RLMs), human liver microsomes (HLMs), and recombinant human CYP3A4 (rCYP3A4) were used to investigate the inhibitory effects and mechanisms of bergapten on macitentan in vitro . In addition, pharmacokinetic parameters were also studied in vivo . Rats were randomly divided into two groups (six rats per group), with or without bergapten (10 mg/kg), and pretreated for 7 days. An oral dose of 20 mg/kg macitentan was administered to each group 30 min after bergapten or 0.5% CMC-Na administration on day 7. Blood was collected from the tail veins, and the plasma concentrations of macitentan and its metabolites were assessed by ultra-performance liquid chromatography - tandem mass spectrometer (UPLC-MS/MS). Finally, we analyzed the binding force of the enzyme and two small ligands by in silico molecular docking to verify the inhibitory effects of bergapten on macitentan. The in vitro results revealed that the IC 50 values for RLMs, HLMs, and rCYP3A4 were 3.84, 17.82 and 12.81 μM, respectively. In vivo pharmacokinetic experiments showed that the AUC (0-t) , AUC (0-∞) , and C max of macitentan in the experimental group (20,263.67 μg/L*h, 20,378.31 μg/L*h and 2,999.69 μg/L, respectively) increased significantly compared with the control group (7,873.97 μg/L*h, 7,897.83 μg/L*h and 1,339.44 μg/L, respectively), while the CL z /F (1.07 L/h/kg) of macitentan and the metabolite-parent ratio (MR) displayed a significant decrease. Bergapten competitively inhibited macitentan metabolism in vitro and altered its pharmacokinetic characteristics in vivo . Further molecular docking analysis was also consistent with the experimental results. This study provides a reference for the combined use of bergapten and macitentan in clinical practice.
研究领域:
药理学
·
药剂学
·
药物化学
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产品关联
DOI
PubMed
高影响因子
AAPS PHARMSCITECH
·
2017
·Vol. 18
·期 8
·2889-2897
·
IF 2.451
Xiong Hui,Fu Jinping,Sun Hanjing,Wang Enfu,Ding Yunhui,Ren Guobin,Jing Qiufang,Ren Fuzheng
Micro-particles of 17β-estradiol (ED) were prepared with polyvinylpyrrolidone (PVP) by in situ pH-dependent solubility technique. Products were characterized using multiple instruments, and molecular interactions between ED and PVP were explored. Powder X-ray diffraction and thermal analysis revealed crystalline ED in the micro-particles is hemihydrated. PVP was also present in the micro-particles. Laser particle size analysis and scanning electron microscopy revealed thin slice morphology, which might have resulted from the influence of PVP. Moreover, the results of contact angle, specific surface area, and dynamic vapor sorption showed that the surface properties of products were improved. These physicochemical properties of the micro-particles resulted in an obvious improvement in dissolution rate. Fourier transform infrared spectroscopy and 1 H nuclear magnetic resonance revealed hydrogen bonding between ED and PVP. A method was established for the preparation of micro-particles through the addition of PVP during the reaction process.
研究领域:
药剂学
·
物理化学
✓ 已验证
DOI
高影响因子
Petroleum Science
·
2023
·
IF 5.6
Shi-Hao Chen,Chuan-Lin Mou,Wen-Long Ma,Ya-Dong Li,Zi-Yu Tang,Hong-Bo Deng
Here, we report the construction of magnetic core-shell microparticles for oil removal with thermal driving regeneration property. Water-in-oil-in water (W/O/W) emulsions from microfluidics are used as templates to prepare core-shell microparticles with magnetic holed poly (ethoxylated trimethylolpropane triacrylate) (PETPTA) shells each containing a thermal-sensitive poly ( N -Isopropylacrylamide) (PNIPAM) core. The microparticles could adsorb oil from water due to the special structure and be collected with a magnetic field. Then, the oil-filled microparticles would be regenerated by thermal stimulus, in which the inner PNIPAM microgels work as thermal-sensitive pistons to force out the adsorbed oil. At the same time, the adsorbed oil would be recycled by distillation. Furthermore, the adsorption capacity of the microparticles for oil keeps very stable after 1st cycle. The adsorption and regeneration performances of the microparticles are greatly affected by the size of the holes on the outer PETPTA shells, which could be precisely controlled by regulating the interfacial forces in W/O/W emulsion templates. The optimized core-shell microparticles show excellent oil adsorption and thermal driving regeneration performances nearly without secondary pollution, and would be a reliable green adsorption material for kinds of oil.
研究领域:
材料科学
·
环境科学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）