RSC Advances
·
2020
·Vol. 10
·期 58
·35141-35152
·
IF 3.119
Xinqiang Li,Han Xing,Zifei Qin,Jing Yang,Peile Wang,Xiaojian Zhang,Zhihong Yao,Xinsheng Yao
Bavachinin, a natural bioactive flavanone, is reported to have many pharmacological proprieties, especially anti-osteoporosis activity. Here we aim to determine the roles of cytochrome P450s (CYP), UDP-glucuronosyltransferases (UGT), and efflux transporters in metabolism and drug–drug interactions (DDI) of bavachinin. Phase I metabolism and glucuronidation were performed by human liver microsomes (HLM) and human intestine microsomes (HIM). Reaction phenotyping was used to identify the main CYPs and UGTs. Gene silencing methods were employed to investigate the roles of breast cancer resistance protein (BCRP) and multidrug resistance-associated proteins (MRPs) in HeLa1A1 cells. Inhibition mechanisms towards CYPs and UGTs were explored through kinetic modeling. Three phase I metabolites (M1–M3) and one glucuronide (G1) were detected after incubation of bavachinin with HLM and HIM. The intrinsic clearance (CLint) values of M1 and G1 by HLM were 89.4 and 270.2 μL min−1 mg−1, respectively, while those of M3 and G1 by HIM were 25.8 and 247.1 μL min−1 mg−1, respectively. CYP1A1, 1A2, 1B1, 2C8, 2C19, and UGT1A1, 1A8 participated more in bavachinin metabolism. The metabolism showed marked species difference. BCRP and MRP4 were identified as the main contributors. Bavachinin displayed potent inhibitory effects against several CYP and UGT isozymes (Ki = 0.28–2.53 μM). Bavachinin was subjected to undergo metabolism and disposition by CYPs, UGTs, BCRP, MRP4, and was also a potent non-selective inhibitor against several CYPs and UGTs.
研究领域:
药理学
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生物化学
·
药物代谢动力学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
·
2018
·
IF 2.831
Zhe Wang,Wei Sun,Zheng-Feng Lin,Rui Sun,Cheng-Ke Huang,Wei-Jian Ye,Yao-Yao Dong,Xiao-Dan Zhang,Rui-Jie Chen
Drug-drug interactions (DDIs) are thought to be associated with the inhibition of cytochrome P450 activities. The cocktail method with analysis of the metabolism of two or more probe drugs is used to determine CYP450 activities. In this study, we established a UHPLC-MS/MS method for simultaneous quantitation of four CYP450 probe drugs (phenacetin, omeprazole, metoprolol and midazolam) and their metabolites (acetaminophen, 5′-hydroxy omeprazole, α-hydroxy metoprolol and 1′-hydroxy midazolam) in rat plasma. Sample preparation by plasma protein precipitation was combined with a liquid-liquid extraction method. The separation was carried out on a ZORBAX Eclipse Plus C18 Rapid Resolution High Definition column with a gradient elution, using water containing 0.1% formic acid (A) and acetonitrile (B) in a run time of only 3.0 min. Detection was conducted with a 6420 series triple-quadrupole tandem mass spectrometer, using ESI in positive ion mode with multiple reaction monitoring (MRM). The calibration curves were linear over the concentration range 10–5000 ng/mL for phenacetin, omeprazole, metoprolol and midazolam, and 1–500 ng/mL for their metabolites. Intra- and inter-day precisions were within 15%, and the accuracies were in the range of 87–112%. The method was successfully applied to the pharmacokinetic study of probe drugs/metabolites and DDIs with 3-n-butylphthalide (NBP) after administration of a single oral dose of phenacetin, omeprazole, metoprolol and midazolam in rats.
研究领域:
药理学
·
分析化学
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临床医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2025
·
IF 4.8
Liming Xie,Guanfeng Chen,Qianqian Ouyang,Weiyan Quan,Xiaoming Xie,Xiaoling Chen,Lefan Li,Sidong Li,Rizhi Chen,Rongqiong Luo,Zhiqing Qiu
Objective: Preventing exposure to hazardous drugs is crucial for healthcare workers to avoid health risks. To mitigate healthcare workers’ risks when handling hazardous drugs, we developed a novel closed-system drug-transfer device (CSTD) called CSTD(JLY). This CSTD has an automatic pressure-relief structure. Hence, it can significantly decrease the resistance in the push/pull of a piston rod if an operator transfers drugs, thereby reducing the burden on the hands of the operator during drug transfer.Methods: We investigated the closed performance of the novel CSTD (JLY) by comparing it with the performance of a syringe. We selected a simulation drug (fluorescein sodium), commonly used drugs (lansoprazole, nimodipine, and tropisetron), and a commonly used anti-cancer agent (cyclophosphamide) to conduct exposure evaluation.Results: Compared with a syringe, CSTD(JLY) could reduce drug leakage significantly. Our novel CSTD with an automatic pressure-relief structure had superior closed performance. CSTD(JLY) could solve the problem of liquid-drug leakage during drug transfer.Conclusion: This feature could reduce the exposure risk healthcare workers and patients.
研究领域:
药学
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医疗安全
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产品关联
DOI
PubMed
高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
·
2021
·
IF 7.46
Zhengxing Song,Jing Wang,Jing Wang,Jin Liu,Xinzhi Wang,Yao Wang,Abdur Raheem Aleem,Matt J. Kipper,Laurence A. Belfiore,Jianguo Tang
Nanoparticle drug delivery systems are designed to be biocompatible and to control the distribution of poorly soluble drugs. Fluorescent nanoparticle drug carriers have been designed to enable fluorescence tracking. While such particles enable tracking of the carrier, this tracking does not report the local drug concentration. In this article, we report new nanoparticle drug carriers with stable, high-intensity fluorescence that sensitively reports the loaded drug concentration. The dumbbell-shaped nanoparticles are synthesized by combining europium (Eu) complexes with hyaluronic acid. The Eu complexes are superior to organic fluorophores, providing a narrow emission peak, high fluorescence intensity, long fluorescence lifetime, and insensitivity to photobleaching. The hyaluronic acid compatibilizes the nanoparticles with aqueous environments, and provides biocompatibility. We demonstrate that these polysaccharide nano-dumbbell aggregates (PNDAs) can effectively load drugs through structural changes, and sense the amount of drug loaded through changes in fluorescence intensity, enabling precise tracking of drug loading and release.
研究领域:
纳米技术
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药学
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生物医学工程
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材料科学
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DOI
高影响因子
JOURNAL OF NANOSCIENCE AND NANOTECHNOLOGY
·
2017
·Vol. 17
·期 6
·3873-3879
·
IF 1.483
Hu Gaoli,Song Botao,Zhu Jie
The aim of this study was to implement a novel bioinspired process based on the superhydrophobic surface to produce organic solvent-free spheres for drug controlled release. Firstly, superhydrophobic substrate with large area was successfully constructed in one step by the electrospray
approach. Then, by utilizing the as-synthesized superhydrophobic substrate the chitosan (CS) spheres with controllable sizes and drug loading contents were fabricated. The drug encapsulation efficiency was further carefully studied, and it was found that the encapsulation efficiencies were
very high and could reach up to 92% and above. Finally, the drug release behaviors of the drug-loaded CS spheres were systematically investigated, and the results demonstrated that both the diameter of the CS spheres and the drug loading content influenced the drug release characteristics.
This present approach opened up a new possibility for the development of novel drug delivery systems with controllable drug delivery property for a broad range of pharmaceutical and biomedical applications.
研究领域:
生物材料学
·
药剂学
✓ 已验证
DOI
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2019
·
IF 3.973
Najaf Ali Soomro,Qiao Wu,Safdar Ali Amur,Hao Liang,Aziz Ur Rahman,Qeping Yuan,Yun Wei
In this study, we have encapsulated natural physcion (PHY) drug loading into metal-organic frameworks MOFs , zeolitic imidazolate frameworks (ZIFs) through straight-forward nano-precipitation technique. The synthesized PHY@ZIF-8 indicated high drug loading encapsulation efficiency i.e. 88%, whereas, drug loading capacity was found to be 11.49%. The characterization of PHY loaded-ZIF 8 (PHY@ZIF-8) was carried out by powder x-ray diffraction (PXRD), transmission electron microscopy (TEM), scanning electron microscopy (SEM), thermal gravimetric analysis (TGA), and FT-IR methods. The release of PHY loaded in ZIF-8 was 88.72% at pH 5.0 which is approximately three time higher than its release in physiological system with pH 7.4 (27.61%). The remarkable stability of PHY@ZIF-8 NPs even after 25 days stem it as an effective and stable candidate. Furthermore, the antibacterial activity of pure PHY, ZIF-8 and PHY@ZIF-8 were investigated against gram negative strains and gram positive strain. The PHY@ZIF-8 showed maximum growth inhibition zones against all microorganism as compare to pure PHY. We hope that this model drug could have the potential ability for treatment of various infectious diseases.
研究领域:
材料科学
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药理学
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微生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
·
2020
·
IF 3.209
Yuhuan Ji,Xueyuan Zhang,Jinzhi Liu,Yu Chen,Min Meng,ChunLei Li,Laixin Wang
Regulatory guidance requires the quantification of encapsulated and free doxorubicin for a liposomal doxorubicin injection bioequivalence study. Due to the instability of liposome formulations in plasma samples, the release of free drug from the liposomal encapsulated doxorubicin during sample handling would result in elevation of measured free doxorubicin concentration. To prevent the potential release of free drug, stabilizer reagents and procedures were successfully developed and validated to adequately stabilize liposomal drugs in plasma samples during sample collection, storage and extraction. Three LC–MS/MS methods were developed and fully validated for direct quantitation of free, encapsulated and total doxorubicin concentrations in human plasma according to relevant regulatory guidance: Method 1: Quantitation of free doxorubicin and doxorubicinol at a linear range of 1−400 ng/mL and 0.5−10 ng/mL, respectively, from stabilizer treated plasma samples using solid phase extraction (SPE); Method 2: Quantitation of encapsulated doxorubicin at a linear range of 50−50,000 ng/mL from the stabilizer treated plasma sample using SPE followed by PPE extraction method; Method 3: Quantitation of total concentration of doxorubicin from untreated plasma samples at a linear range of 50−50,000 ng/mL using PPE. All three methods were successfully used to support a bioequivalence study between Caelyx® and Duomeisu® (Doxorubicin Hydrochloride Liposomal injection, generic doxorubicin formulation produced by CSPC). Incurred sample reanalysis (ISR) passing rate for total doxorubicin, free doxorubicin/doxorubicinol, and encapsulated doxorubicin methods were 100 %, 84.7 %/100 %, and 98.5 %, respectively. The measured total doxorubicin concentrations matched the sum of free and encapsulated doxorubicin concentrations.
研究领域:
药代动力学
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分析化学
·
药物化学
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产品关联
DOI
PubMed
高影响因子
ACS Chemical Neuroscience
·
2018
·
IF 4.211
Yunong Li,Haixia Zhu,Jingbo Yang,Kehui Ke,Yanmei Zhu,Li Chen,Youyang Qu,Rui Suo,Xiujie Chen,Yulan Zhu
As an important protective mechanism against cerebral ischemia, angiogenesis has become a topic of interest in the treatment of ischemic stroke with the challenge that few drugs promote angiogenesis. Previous studies of the identification of drug–target interactions mainly focused on the overall structures of drugs and proteins, which limited the discovery of novel structure drugs. In this article, we proposed a new strategy for discovering proangiogenic drugs based on the assumption that drug–protein interaction is mediated by substructure and domain. First, we identified substructure–domain relationships according to the known drug–protein interactions and established the drug–substructure–domain–protein relationships of genes that are proangiogenic in brain tissue and expressed significantly during ischemic stroke. Then we quantified the intensity of interaction between each drug and each protein. Finally, we obtained 540 interactive relationships between 238 drugs and 54 genes, establishing a drug–gene network with two patterns of independent and complex drug–gene interactions. Both of the patterns facilitated finding not only drugs with the same overall structure but also drugs with a different overall structure based on the same or a similar protein spectrum. In addition, we analyzed the mechanism of action of each predicted drug and extracted drugs with similar mechanisms. In vitro, our results showed that azelnidipine, azilsartan, lercanidipine, nafcillin, and vortioxetine enhanced bEnd.3 cell proliferation, migration, tube formation, and the expression of angiogenic marker PCNA. Azelnidipine, azilsartan, lercanidipine, and nafcillin increased the level of expression of proangiogenic factor VEGF. Unlike previous studies focusing on the overall structures of drugs, our research highlighted local structural similarity, which has great potential in the search for more proangiogenic drugs with novel structures.
研究领域:
药理学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
AAPS PHARMSCITECH
·
2014
·Vol. 15
·期 3
·731-740
·
IF 1.776
Zhang Jianbin,Lv Yan,Zhao Shan,Wang Bing,Tan Mingqian,Xie Hongguo,Lv Guojun,Ma Xiaojun
The objective of this study is to investigate the effect of lipolysis on the release of poorly water-soluble drug from SMEDDS in the perspective of drug core/shell location. For this purpose, four SMEDDS formulations with various core/shell properties were developed based on long-chain lipid or medium-chain lipid as well as different surfactant/oil ratios. Poorly water-soluble drugs, hymecromone and resveratrol, were significantly solubilized in all SMEDDS formulations and the diluted microemulsions. Fluorescence spectra analysis indicated that hymecromone was mainly located in the shell of microemulsions, while resveratrol was located in the core. The effect of lipolysis on the release rates of drugs with different core/shell locations were investigated by a modified in vitro drug release model. For the drug located in the shell, hymecromone, the release profiles were not affected during the lipolysis process and no significant differences were observed among four formulations. For the drug located in the core, resveratrol, the release rates were increased to various degrees depending on the extent of digestion. In conclusion, the drug core/shell location plays an important role for determining the effect of lipolysis on drug release from SMEDDS formulation.
研究领域:
药剂学
·
生物医学工程
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产品关联
DOI
PubMed
高影响因子
DRUG METABOLISM AND DISPOSITION
·
2025
·
IF 4
Dafa Yi,Jiazong Ye,Zebei Lu,Leilei Lu,Tengfei Qi,Tong Luo,Xiuyun Peng,Abdullah Al Mamun,Quan Zhou,Daqing Chen,Shuanghu Wang
This study investigates the potential drug-drug interactions between commonly prescribed anti-hypertensive drugs and mobocertinib in clinical practice to provide the scientific basis for the appropriate therapeutic application of drugs. The study used UPLC-MS/MS to detect the essential metabolites of mobocertinib in rat liver microsomes. Moreover, several anti-hypertensive drugs were used as inhibitors and the IC 50 values were determined for calcium channel blockers, angiotensin II receptor blockers and α and β receptor blockers against mobocertinib. The inhibitory mechanism of mobocertinib was further investigated for nicardipine, irbesartan, telmisartan, carvedilol, prazosin hydrochloride and spironolactone. Twenty-five Sprague Dawley ( SD) rats were randomly divided into five groups: benidipine, nicardipine, telmisartan, irbesartan and blank control groups. The drugs were administered over a period of 7 days. Mobocertinib was administered once by gavage to five groups and then blood samples were collected for further analysis. UPLC-MS/MS was performed to analyze the concentration of mobocertinib and its metabolites in rat plasma. Most anti-hypertensive drugs were found to inhibit the metabolism of mobocertinib in vitro. Several anti-hypertensive drugs were also found to increase the plasma concentration and decrease the metabolic rate of mobocertinib when administered multiple times. More importantly, we found that benidipine, nicardipine, telmisartan and irbesartan inhibited the metabolism of mobocertinib in vitro and in vivo . In summary, our data reveal that anti-hypertensive drugs interact with mobocertinib and additional attention is needed when co-administering the two drugs.
研究领域:
药理学
·
临床医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
TOXICOLOGY LETTERS
·
2021
·
IF 4.374
Zhe Wang,Xiaoyu Wang,Zhen Wang,Yaqin Jia,Yuyi Feng,Lili Jiang,Yangliu Xia,Jun Cao,Yong Liu
Osimertinib is the only third-generation epidermal growth factor receptor tyrosine-kinase inhibitor (EGFR-TKI) approved by Food and Drug Administration (FDA). This study aimed to know the inhibitory effect of osimertinib on human UDP-glucosyltransferases (UGTs) and human liver microsomes (HLMs), as well as to identify its potential to cause drug-drug interaction (DDI) arising from the modulation of UGT activity. High inhibitory effect of osimertinib was shown towards UGT1A1, 1A3, 1A6, 1A7, 1A8, 1A10, 2B7 and 2B15. Especially, osimertinib exhibited competitive inhibition against UGT1A1 with a K i,u of 0.87 ± 0.12 μM. It also noncompetitively inhibited SN-38 glucuronidation in pooled HLMs with a K i,u of 3.32 ± 0.25 μM. Results from quantitative prediction study indicated that osimertinib administered at 80 mg/day may result in a 4.83 % increase in the AUC of drugs mainly metabolized by UGT1A1, implying low risk of DDI via liver metabolism. However, the ratios of [ I ] gut / K i,u are much higher than 11 in HLMs and recombinant UGT1A1, indicating a risk for interaction in intestine. The effects of osimertinib on intestinal UGT should be paid more attention on to avoid unnecessary clinical DDI risks.
研究领域:
药理学
·
临床医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
SYNTHETIC METALS
·
2013
·
IF 2.109
Shuhui Jiang,Yanan Sun,Xin Cui,Xiang Huang,Yuan He,Shan Ji,Wei Shi,Dongtao Ge
For a conducting polymer (CP) based drug release system, drug loading is often accomplished by a doping process, in which drug is incorporated into polymer as dopant. Therefore, the drug loading capacity is relatively low and the range of drugs can be loaded is limited. In the present work, a polypyrrole (PPy) nanowire network is prepared by an electrochemical method and it is found that the micro- and nano-gaps among the individual nanowires of the PPy nanowire network can be used as reservoir to store drugs. Therefore, the drug loading capacity is dependent on the volume of these micro- and nano-vacancies, instead of the doping level. The range of loaded drugs also can be theoretically extended to any drugs, instead of only charged dopants. In fact, it is confirmed here that both hydrophilic and lipophilic drugs can be loaded into the micro- and nano-gaps due to the amphilicity of the PPy nanowire network. As a result, both drug loading capacity and the range of drugs can be loaded are significantly improved. After being covered with a protective PPy film, controlled drug release from the prepared system is achieved by electrical stimulation (cyclic voltammetry, CV) and the amount of drug released can be controlled by changing the scan rate of CV and the thickness of the protective PPy film.
研究领域:
生物医学工程
·
材料科学
✓ 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）