Drug Design Development and Therapy
·
2017
·
IF 2.822
Jieyun Huang,Zhi Chen,Ying Li,Li Li,Guangyu Zhang
In this study, we aimed to design controlled-release microspheres for the treatment of cavitary pulmonary tuberculosis (TB) for solving the issues of poor drug delivery and short duration maintained at effective drug concentration during bronchoscopic interventional therapy. We fabricated rifapentine-linezolid-loaded poly(lactic acid-co-glycolic acid) microspheres (RLPMs) using the oil-in-water emulsion solvent evaporation method and assessed their in vitro release as well as the bronchial mucosal retention characteristics. The microspheres are spherical in shape with a circular concave on the surface. The particle size of RLPMs was 27.38±1.28 μm. The drug loading of rifapentine and linezolid was 18.51±0.26 and 8.42%±0.24%, respectively, while the encapsulation efficiencies were 55.53±0.78 and 16.87%±0.47%, respectively (n=3). During the burst release phase of the in vitro release test, 21.37%±0.68% rifapentine was released in 3 days and 43.56%±2.54% linezolid was released in 1 day. Then, both the drugs entered the sustained release phase. Finally, the cumulative percentage release of rifapentine and linezolid in 14 days was 27.61±1.52 and 51.01%±3.31%, respectively (n=3). Bronchoscopic observation revealed that the controlled-release microspheres could slowly release the drugs and retain them on the surface of bronchial mucosa of canines for 20 days. These results indicated that the fabricated microspheres exhibited a significant sustained release effect and could effectively retain the drugs on the surface of bronchial mucosa. Therefore, this study provides a theoretical and practical foundation for the development of fabricated microspheres loaded with multiple anti-TB drugs in the bronchoscopic interventional therapy of cavity pulmonary TB.
研究领域:
药剂学
·
呼吸病学
·
感染病学
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产品关联
DOI
PubMed
高影响因子
CRYSTENGCOMM
·
2024
·
IF 2.6
Xiaowen Zhang,Dongshuo Meng,Zongwu Zang,Zhiru Xu,Yu Liu
Bedaquiline (BDQ) is an orally administered diarylquinoline class anti-tuberculosis drug used in the combination therapy of MDR-TB. Currently, it is marketed as bedaquiline fumarate (BDQ–FA). However, due to its poor water solubility, BDQ–FA must be taken with food to enhance bioavailability. Concurrent administration reduces patient compliance and may increase the risk of inconsistent serum levels due to differences in dietary habits. This study designed and synthesized the saccharin salt of bedaquiline (BDQ–SA). Compared to the marketed fumarate salt, BDQ–SA exhibits better solubility and absorption. The food effect of commercially available BDQ–FA in beagle dogs was 7.2 times, while that of BDQ–SA was 3.2 times. This study provides a good example of using a new salt form to improve drug solubility and mitigate the food effect of the drug.
研究领域:
药学
·
传染病学
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产品关联
DOI
高影响因子
Frontiers in Molecular Biosciences
·
2022
·
IF 6.113
Zheng Judun,Long Xun,Chen Hao,Ji Zhisheng,Shu Bowen,Yue Rui,Liao Yechun,Ma Shengchao,Qiao Kun,Liu Ying,Liao Yuhui
Tuberculosis (TB) is a virulent form of an infectious disease that causes a global burden due to its high infectivity and fatality rate, especially the irrepressible threats of latent infection. Constructing an efficient strategy for the prevention and control of TB is of great significance. Fortunately, we found that granulomas are endowed with higher reducibility levels possibly caused by internal inflammation and a relatively enclosed microenvironment. Therefore, we developed the first targeted glutathione- (GSH-) responsive theranostic system (RIF@Cy5.5-HA-NG) for tuberculosis with a rifampicin- (RIF-) loaded near-infrared emission carrier, which was constructed by photoclick reaction-actuated hydrophobic-hydrophobic interaction, enabling the early diagnosis of tuberculosis through granulomas-tracking. Furthermore, the loaded rifampicin was released through the dissociation of disulfide bond by the localized GSH in granulomas, realizing the targeted tuberculosis therapy and providing an especially accurate treatment mapping for tuberculosis. Thus, this targeted theranostic strategy for tuberculosis exhibits the potential to realize both granulomas-tracking and anti-infection of tuberculosis.
研究领域:
医学
·
药理学
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产品关联
DOI
PubMed
高影响因子
mSphere
·
2025
·
IF 3.1
Xinda Li,Xiaoyi Luo,Bin Wang,Lei Fu,Xi Chen,Yu Lu
Drug-resistant tuberculosis (DR-TB) urgently requires safer, more accessible alternatives to bedaquiline (BDQ), which faces critical flaws like cardiotoxicity, high costs, and emerging resistance. WX-081, a promising BDQ alternative, has demonstrated superior anti-TB activity and improved safety in clinical studies. However, its mechanism of action remains unexplored, underscoring the need for further research to optimize its potential in advancing global TB elimination efforts. This study reveals WX-081’s dual mechanisms: targeting atpE to disrupt ATP synthase and proton motive force via resistance screening, gene sequencing, and functional assays while enhancing host immunity through macrophage transcriptomics. Molecular docking confirmed atpE binding sites, and immune activation pathways (NF-κB/MAPK) were identified, positioning WX-081 as a potent, safe anti-DR-TB candidate despite unresolved mechanistic details.
研究领域:
微生物学
·
药物研发
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免疫学
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产品关联
DOI
PubMed
高影响因子
PLoS One
·
2015
·Vol. 10
·期 3
·e0116832
·
IF 3.234
Yan-Ling Zheng,Li-Ping Zhang,Xue-Liang Zhang,Kai Wang,Yu-Jian Zheng
Tuberculosis is a major global public health problem, which also affects economic and social development. China has the second largest burden of tuberculosis in the world. The tuberculosis morbidity in Xinjiang is much higher than the national situation; therefore, there is an urgent need for monitoring and predicting tuberculosis morbidity so as to make the control of tuberculosis more effective. Recently, the Box-Jenkins approach, specifically the autoregressive integrated moving average (ARIMA) model, is typically applied to predict the morbidity of infectious diseases; it can take into account changing trends, periodic changes, and random disturbances in time series. Autoregressive conditional heteroscedasticity (ARCH) models are the prevalent tools used to deal with time series heteroscedasticity. In this study, based on the data of the tuberculosis morbidity from January 2004 to June 2014 in Xinjiang, we establish the single ARIMA (1, 1, 2) (1, 1, 1) 12 model and the combined ARIMA (1, 1, 2) (1, 1, 1) 12 -ARCH (1) model, which can be used to predict the tuberculosis morbidity successfully in Xinjiang. Comparative analyses show that the combined model is more effective. To the best of our knowledge, this is the first study to establish the ARIMA model and ARIMA-ARCH model for prediction and monitoring the monthly morbidity of tuberculosis in Xinjiang. Based on the results of this study, the ARIMA (1, 1, 2) (1, 1, 1) 12 -ARCH (1) model is suggested to give tuberculosis surveillance by providing estimates on tuberculosis morbidity trends in Xinjiang, China.
研究领域:
流行病学
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传染病学
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生物统计学
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公共卫生
·
预防医学
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DOI
高影响因子
MONATSHEFTE FUR CHEMIE
·
2024
·
IF 1.7
Qiu Shengzhou,Wu Chenxi,Akter Sima,Hong Shaoli,Liu Huihong,Mahmud Sakil
Addressing the challenges of tuberculosis drug detection, this study investigates the application of copper(II) oxide modified screen-printed carbon electrodes (CuO/SPCEs) for the electrochemical detection of rifampicin, a critical drug in the treatment of tuberculosis and mycobacterial infections. The CuO/SPCE was fabricated via a constant potential electrodeposition technique and characterized using voltammetry. The bare SPCE surface exhibited a rough, porous structure, whereas the electrodeposition of CuO resulted in a smoother CuO/SPCE surface. The sensor exhibited high sensitivity with a detection limit of 2.89 μM for rifampicin and demonstrated excellent stability with a relative standard deviation of 3.5% over 10 measurements. The reproducibility was confirmed with an RSD of 4.2% across different electrodes. It also showed a linear response to rifampicin concentrations ranging from 10 to 200 μM. The real sample analysis showed a linear relationship between rifampicin concentration and peak current ( I = 0.739 + 0.008 c ), with a high correlation coefficient ( R 2 = 0.995). This electrochemical sensor’s simplicity, cost-effectiveness, and rapid response make it a promising tool for point-of-care applications in tuberculosis management. Graphical abstract
研究领域:
医学诊断
·
药物分析
·
生物传感器
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产品关联
DOI
高影响因子
MICROCHIMICA ACTA
·
2013
·Vol. 180
·期 5
·431-436
·
IF 3.434
Chen Hongxia,Liu Feng,Koh Kwangnak,Lee Jaebeom,Ye Zonghuang,Yin Tingting,Sun Lizhou
We show that the antigen CFP-10 (found in tissue fluids of tuberculosis patients) can be used as a marker protein in a surface-plasmon resonance (SPR) based method for early and simplified diagnosis of tuberculosis. A sandwich SPR immunosensor was constructed by immobilizing the CFP-10 antibody on a self-assembled monolayer on a gold surface, this followed by blocking it with bovine serum albumin. Following exposure of the sensor surface to a sample containing CFP-10, secondary antibody immobilized on nickel oxide nanoparticles are injected which causes a large SPR signal change. The method has a dynamic range from 0.1 to around 150 ng per mL of CFP-10, and a detection limit as low as 0.1 ng per mL. This is assumed to be due to the high amplification power of the NiO nanoparticles.
Schematic diagram of sensor chip configuration (left) and SPR study based on amplification strategy with NiO nanoparticles (right).
研究领域:
医学诊断
·
生物传感
·
纳米技术
✓ 已验证
产品关联
DOI
高影响因子
ANALYST
·
2025
·
IF 3.3
Jiahui Lai,Danni Wang,Xiuqin Sheng,Chuan-Fan Ding,Yinghua Yan
In large-scale glycoproteomics studies, reducing the experimental duration and enhancing digestion efficiency are crucial. In this work, a magnetic nanomaterial featuring a surface rich in hydrophilic groups and uniformly distributed trypsin (Fe3O4@DOPA/PEI@Au@DNA TET-trypsin) was developed for efficient digestion of proteins and specific enrichment of glycopeptides. The material surface exhibits a regular distribution of trypsin coupled with abundant hydrophilic groups. Thus, the material can demonstrate excellent performance in experimental studies related to glycoproteomics. Fe3O4@DOPA/PEI@Au@DNA TET-trypsin showed an excellent limit of detection (0.001 amol·μL−1) and high selectivity for glycopeptides (BSA : HRP = 5000 : 1) in a short reaction time, and it showed good performance in the processing of practical samples. Gene Ontology (GO) analysis suggests that complement activation, extracellular space, antioxidant activity and complement binding may be associated with tuberculosis. These analytical results provide new insights for determining and clarifying the pathogenesis and pathology related to tuberculosis.
研究领域:
蛋白质组学
·
生物化学
·
医学
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产品关联
DOI
PubMed
高影响因子
BIOSENSORS & BIOELECTRONICS
·
2015
·
IF 6.409
Zhongdan Yan,Ning Gan,Huairong Zhang,De Wang,Li Qiao,Yuting Cao,Tianhua Li,Futao Hu
A novel sandwich-hybridization assay for simultaneous electrochemical detection of multiple DNA targets related to human immune deficiency virus (HIV) and tuberculosis (TB) was developed based on the different quantum dots-PowerVision TM polymer nanotracers. The polymer nanotracers were respectively fabricated by immobilizing SH-labeled oligonucleotides (s-HIV or s-TB), which can partially hybrid with virus DNA (HIV or TB), on gold nanoparticles (Au NPs) and then modified with PowerVision TM (PV) polymer-encapsulated quantum dots (CdS or PbS) as signal tags. PV is a dendrimer enzyme linked polymer, which can immobilize abundant QDs to amplify the stripping voltammetry signals from the metal ions (Pb or Cd). The capture probes were prepared through the immobilization of SH-labeled oligonucleotides, which can complementary with HIV and TB DNA, on the magnetic Fe 3 O 4 @Au (GMPs) beads. After sandwich-hybridization, the polymer nanotracers together with HIV and TB DNA targets were simultaneously introduced onto the surface of GMPs. Then the two encoding metal ions (Cd 2+ and Pb 2+ ) were used to differentiate two viruses DNA due to the different subsequent anodic stripping voltammetric peaks at −0.84 V (Cd) and −0.61 V (Pb). Because of the excellent signal amplification of the polymer nanotracers and the great specificity of DNA targets, this assay could detect targets DNA as low as 0.2 femtomolar and exhibited excellent selectivity with the dynamitic range from 0.5 fM to 500 pM. Those results demonstrated that this electrochemical coding assay has great potential in applications for screening more viruses DNA while changing the probes.
研究领域:
生物医学工程
·
分子诊断学
·
纳米技术
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产品关联
DOI
PubMed
高影响因子
MICROCHEMICAL JOURNAL
·
2022
·
IF 5.304
Jiang Chang,Deying Zou,Honglin Ren,Xilin Liu,Meng Li,Zhaozhao Si,Cheng Han,Zengshan Liu,Shiying Lu,Pan Hu
The 10-kDa chemokine interferon-gamma-inducible protein 10 (IP-10) is considered one of the most promising biomarkers for diagnosing both tuberculosis and COVID-19 infections. The blood samples of patients at different disease states contain different levels of IP-10, which need to be detected in a rapid, specific and ultrasensitive manner. Here, we report a bienzymatic chemiluminescence sandwich immunoassay (BCSI) assay for the ultrasensitive and stable detection of IP-10. In this assay, IP-10 is first efficiently captured using a double-antibody sandwich strategy. The detection antibody is linked to catalase (CAT) via a streptavidin–biotin signal amplification system to achieve highly efficient conversion of hydrogen peroxide (H 2 O 2 ) to oxygen and water. In the chemiluminescence (CL) reaction, horseradish peroxidase (HRP) acts as an efficient catalyst, and 4-bromophenol acts as an enhancer for the cyclic transition of HRP, which results in a strong and durable CL signal. The bienzymatic catalysis with CAT and HRP and the potentiation of 4-bromophenol enables the assay to be ultrasensitive and stable. The CL intensity was found to be well correlated with the detection of IP-10 at levels in the range of 0.71 to 125,000 pg/mL, which covers more than 6 orders of magnitude, with a detection limit of 0.63 pg/mL. The coefficient of variation was 1.49%, and the recovery range of IP-10 in serum was 86.21%-104.57%. This assay provides a wide linear range and high sensitivity and may be a promising method for the high-throughput detection of IP-10 in the diagnosis of tuberculosis and COVID-19.
研究领域:
医学诊断
·
免疫学
·
化学生物学
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产品关联
DOI
高影响因子
Materials Science & Engineering C-Materials for Biological Applications
·
2017
·
IF 4.164
Chili Zhao,Xun Liu,Xia Zhang,Hong Yan,Zhilei Qian,Xinghui Li,Zhenye Ma,Qiaorong Han,Chonghua Pei
In this paper, Fe 3 O 4 /chitosan/isoniazid magnetic nanoparticles (Fe 3 O 4 /CS/INH-MNPs) were prepared as an environmental stimuli-responsive drug-delivery system by automated in situ click technology, in which Fe 3 O 4 magnetic nanoparticles, chitosan and isoniazid were simultaneously in situ crystallized by one-step method. The Fe 3 O 4 magnetic nanoparticles and tripolyphosphate act as stable crosslinkers to produce numerous intermolecular crosslinkages for the mobility of the chitosan chains. Characterization results indicated that the multifunctional drug delivery system with optimized size, excellent loading capacity, well magnetic properties, nontoxicity and pH triggered drug release property is expected to be applied in tuberculosis treatment with excellent magnetic sensitivity and sustained release.
研究领域:
药学
·
生物医学工程
·
纳米医学
✓ 已验证
DOI
高影响因子
ACS Sensors
·
2022
·
IF 9.618
Ou Hu,Zeyu Li,Jinghao Wu,Yaoju Tan,Zuanguang Chen,Yanli Tong
Clinical tuberculosis (TB) screening and diagnosis are crucial for controlling the spread of this life-threatening infectious disease. In this work, a novel, rapid, and simple colorimetric detection platform for TB was developed based on a quantum dot-based nanobeacon (QD-NB) and multicomponent nucleic acid enzyme (MNAzyme). In the presence of target DNA (IS1081 gene fragment), the recombinase polymerase amplification (RPA) was performed and the amplicons were chemically DNA-denatured and then subjected to MNAzyme reaction. RNA-cleaving MNAzyme assembly included the recognition of target DNA and hybridization with a QD-NB fluorescence probe. Under the addition of Mg2+, the RNA-containing QD-NB as a cleavable substrate could be broken into two DNA fragments, leading to green fluorescence release due to their departure from a black hole quencher (BHQ2). The TB detection could be achieved with the naked eye under a portable and inexpensive UV flashlight. Our results demonstrated that QD-NB-based MNAzyme colorimetric assays improved the detection sensitivity by 1 order of magnitude compared with the detection using RPA. The limit of detection (LOD) of the visual reading was as low as 2 copies/μL (3.3 amol/L). Excellent specificity and reproducibility could also be achieved. Furthermore, the practical application of the colorimetric method for TB diagnosis was verified by 36 clinical TB patients and 20 healthy individuals. The developed QD-NB-based MNAzyme colorimetric assays provided a rapid, convenient, sensitive, and accurate alternative for clinical TB screening and diagnosis.
研究领域:
分子生物学
·
医学诊断
·
纳米技术
✓ 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）