Assay and drug development technologies最新文献_第8页

Development and Method Validation of Design of Experiments-Optimized Tablet Formulation for Simultaneous Detection of Exemestane and Everolimus. 同时检测依西美坦和依维莫司的优化片剂配方实验设计的开发和方法验证。

IF 1.8 4区医学

Assay and drug development technologies Pub Date : 2023-08-01 Epub Date: 2023-09-08 DOI: 10.1089/adt.2023.055

Akshay Kumar, Balak Das Kurmi, Dilpreet Singh

{"title":"Development and Method Validation of Design of Experiments-Optimized Tablet Formulation for Simultaneous Detection of Exemestane and Everolimus.","authors":"Akshay Kumar, Balak Das Kurmi, Dilpreet Singh","doi":"10.1089/adt.2023.055","DOIUrl":"10.1089/adt.2023.055","url":null,"abstract":"The development and analysis of pharmaceutical formulations often involves the determination of multiple active ingredients in a dosage form. The aim of the present study is to develop a convenient method for simultaneous estimation of Exemestane (EXE) and Everolimus (EVE) in bulk and in systemically designed tablet dosage form. Methanol was used as a solvent for developing linear curves and validated in terms of various parameters, such as selectivity, sensitivity, linearity, precision, accuracy, and robustness. Method validation observed that the proposed method is reliable and reproducible, meeting the regulatory requirements for pharmaceutical analysis with a relative standard deviation of <2%. The developed method was found to be sensitive and selective in simultaneous equation method. The unknown concentrations of EVE and EXE were found to be 10.431 and 10.232, respectively. The next step is to systematically design a tablet formulation for EXE and EVE containing β-cyclodextrin as a polymer. Microcrystalline cellulose (X1), sodium starch glycolate (X2), and beta-cyclodextrin (X3) are the critical variables and hardness (Y2) and friability (Y3) were selected as prime responses. Analysis of variance provides significance of the model, and the predicted batch gives a high desirability value of 0.862. In vitro dissolution profiles of optimized batch (OB1) were signified by high drug release profile as 89.47% and 96.00% for EVE and EXE in tablet formulation, as compared with pure API, respectively. This study signifies enhancement in biopharmaceutical attributes of EXE and EVE in tablet formulation and robust simultaneous estimation by the UV method. In a nutshell, this study provides the simultaneous estimation method in tablet dosage form, and further research is crucial for the advancement of pharmaceutical analysis and the formulation of effective medicines.","PeriodicalId":8586,"journal":{"name":"Assay and drug development technologies","volume":"21 6","pages":"273-287"},"PeriodicalIF":1.8,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10358250","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Psoriasis: Striving for Potential Biomarkers. 银屑病：寻找潜在的生物标志物。

IF 1.8 4区医学

Assay and drug development technologies Pub Date : 2023-08-01 Epub Date: 2023-09-05 DOI: 10.1089/adt.2023.014

Deblina Dan, Nimisha Srivastava

{"title":"Psoriasis: Striving for Potential Biomarkers.","authors":"Deblina Dan, Nimisha Srivastava","doi":"10.1089/adt.2023.014","DOIUrl":"10.1089/adt.2023.014","url":null,"abstract":"Psoriasis is a chronic disease that is caused by multiple factors and is identified by itchiness, unpleasant, red, or white scaly patches on the skin, particularly on regularly chafed body regions such as the lateral areas of the limbs. Reports suggest that globally around 2%-3% of the population suffers from psoriasis. In this review, we have discussed the clinical classification of psoriasis and also the ideal characteristics of the biomarkers. An overview regarding the discovery of the biomarker and method for validating the study has been discussed. A growing body of research suggests a link to certain other systemic symptoms such as cardiovascular disorder, metabolic syndrome, and few other comorbidities such as hypertension and nonalcoholic fatty liver disease. Natural killer (NK) cells are lymphocyte cells that concentrate on the destruction of virally infected and malignant cells; these tend to produce a wide range of inflammatory cytokines, some of which are associated with the etiology of psoriasis. Detailed information on the molecular pathogenesis of psoriasis in which interleukin (IL)-17, IL-23, tumor necrosis factor-α (TNF-α), and CCL20 play a very significant role in the development of psoriasis. In this review, we have discussed an overview of the recent state of the biomarkers available for the diagnosis and treatment of psoriasis by emphasizing on the available biomarkers such as epigenomic, transcriptomic, glycomic, and metabolomic. The most recent advancements in molecular-targeted therapy utilizing biologics and oral systemic therapy (methotrexate, apremilast) enable to adequately treat the most serious psoriatic symptoms and also the studies have validated the efficacy of biologic therapy such as TNF-α antagonist (infliximab, adalimumab), IL-23 antagonist (guselkumab, risankizumab), and IL-17 antagonist (secukinumab, ixekizumab). Finally, an overview about the technological opportunities as well as various challenges has been discussed.","PeriodicalId":8586,"journal":{"name":"Assay and drug development technologies","volume":"21 6","pages":"235-257"},"PeriodicalIF":1.8,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10307237","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Correction to: Enhanced Cytotoxic Activity of 6-Mercaptopurine-Loaded Solid Lipid Nanoparticles in Hepatic Cancer Treatment, by Ergin, et al. Assay Drug Dev Technol. 2023;21(5):212-221; doi: 10.1089/adt.2023.007. 修正：6-巯基嘌呤负载固体脂质纳米粒子在癌症治疗中增强的细胞毒性活性，Ergin等人，Assay Drug Dev Technol。2023年；21（5）：212-221；doi:10.1089/日期.2023.007。

IF 1.8 4区医学

Assay and drug development technologies Pub Date : 2023-08-01 Epub Date: 2023-09-06 DOI: 10.1089/adt.2023.007.correx

引用次数: 0

Exploration of the Mechanism of Shengxian Decoction Against Chronic Obstructive Pulmonary Disease Based on Network Pharmacology and Experimental Verification. 基于网络药理学和实验验证的升仙汤抗慢性阻塞性肺疾病作用机制探讨。

IF 1.8 4区医学

Assay and drug development technologies Pub Date : 2023-08-01 Epub Date: 2023-09-08 DOI: 10.1089/adt.2023.006

Yifei Chen, Yiming Wang, Zheng Li, Jing Jing, De Jiang, Xiaoxia Yuan, Fengsen Li

{"title":"Exploration of the Mechanism of Shengxian Decoction Against Chronic Obstructive Pulmonary Disease Based on Network Pharmacology and Experimental Verification.","authors":"Yifei Chen, Yiming Wang, Zheng Li, Jing Jing, De Jiang, Xiaoxia Yuan, Fengsen Li","doi":"10.1089/adt.2023.006","DOIUrl":"10.1089/adt.2023.006","url":null,"abstract":"Shengxian decoction (SXT) is clinically used in chronic obstructive pulmonary disease (COPD) treatment. This study aimed to explore the mechanism and target genes of SXT acting on COPD. Differentially expressed genes (DEGs) between COPD and controls were identified and then performed enrichment analysis. The effective active compounds and corresponding target genes were obtained from the traditional Chinese medicine systems pharmacology database. We also compiled COPD related genes from the GeneCards database. Through the protein-protein interaction (PPI) network and least absolute shrinkage and selection operator (LASSO) regression was performed to identify key genes. Molecular docking was used for docking of key genes and compounds. The expression of key genes was detected by quantitative real-time PCR in COPD patients and bronchial epithelial cells stimulated with cigarette stroke extract (CSE). We identified 1,458 intersected DEGs from GSE47460 and GSE57148 datasets. Compared with intersected DEGs, we obtained 33 SXT target COPD-related genes. PI3K-Akt signaling pathway, MAPK signaling pathway, and focal adhesion were enriched by these 33 genes, as well as intersected DEGs. According to LASSO regression, there were 12 genes considered as signature genes. Then we constructed active compounds and corresponding six target genes. Finally, HIF1A and IL1B were selected as key genes by combining PPI network. HIF1A and IL1B were all upregulated expression in COPD and CSE stimulated cells and recovered in SXT treated CSE stimulated cells. This study provides a scientific basis for the identification of active compounds and target genes of SXT in the treatment of COPD.","PeriodicalId":8586,"journal":{"name":"Assay and drug development technologies","volume":"21 6","pages":"258-272"},"PeriodicalIF":1.8,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10297899","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Drug Repurposing Patent Applications April-June 2023. 药物再利用专利申请2023年4月至6月。

IF 1.8 4区医学

Assay and drug development technologies Pub Date : 2023-08-01 Epub Date: 2023-09-01 DOI: 10.1089/adt.2023.081

Hermann A M Mucke

引用次数: 0

Rosalind Franklin Society Proudly Announces the 2022 Award Recipient for Assay and Drug Development Technologies. 罗莎琳德·富兰克林协会自豪地宣布了2022年测定和药物开发技术奖获得者。

IF 1.8 4区医学

Assay and drug development technologies Pub Date : 2023-07-01 DOI: 10.1089/adt.2023.29104.rfs2022

Anaelle da Costa

引用次数: 0

Enhanced Cytotoxic Activity of 6-Mercaptopurine-Loaded Solid Lipid Nanoparticles in Hepatic Cancer Treatment. 6-巯基嘌呤负载的固体脂质纳米颗粒在肝癌治疗中的细胞毒活性增强。

IF 1.8 4区医学

Assay and drug development technologies Pub Date : 2023-07-01 DOI: 10.1089/adt.2023.007

Ahmet Doğan Ergin, Çağatay Oltulu, Büşra Koç

{"title":"Enhanced Cytotoxic Activity of 6-Mercaptopurine-Loaded Solid Lipid Nanoparticles in Hepatic Cancer Treatment.","authors":"Ahmet Doğan Ergin, Çağatay Oltulu, Büşra Koç","doi":"10.1089/adt.2023.007","DOIUrl":"https://doi.org/10.1089/adt.2023.007","url":null,"abstract":"6-Mercaptopurine (6-MCP) is an antiproliferative purine analog used in acute lymphoblastic leukemia, non-Hodgkin lymphoma, and inflammatory bowel disease (Crohn's disease, ulcerative colitis). Although 6-MCP has the great therapeutic potential for cancer and immunosuppressant-related diseases, 6-MCP is not readily soluble in water, presents a high first-pass effect, short half-life (0.5-1.5 h), and implies a low bioavailability (16%). On the contrary, solid lipid nanoparticles (SLNs) are prepared from solid lipids at room temperature and body temperature. In this study, SLNs were prepared w/o/w double emulsion-solvent evaporation method using Precirol ATO5 as matrix lipid. In the emulsion stabilization, surfactant (Tween 80) and polymeric stabilizer (polyvinyl alcohol [PVA]) were used. Two group formulations using Tween 80 and PVA were compared in terms of particle size, polydispersity index, zeta potential encapsulation efficiency%, and process yield%. Differential calorimetric analysis and release properties were examined for optimum formulation, and release kinetics were calculated. According to studies, sustained release was obtained with SLNs by the Korsmayer-Peppas kinetic model. The in vitro cytotoxicity studies were performed on the hepatocarcinoma (HEP3G) cell line. According to the results, successful SLN formulations were produced, and PVA was found best stabilizer. Optimum formulation exhibited significantly higher cytotoxic effects on HEP3G than on pure 6-MCP. These results demonstrated that solid lipid nanodrug delivery systems have great potential for formulation of 6-MCP.","PeriodicalId":8586,"journal":{"name":"Assay and drug development technologies","volume":"21 5","pages":"212-221"},"PeriodicalIF":1.8,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10519881","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Biosensor Assays Types and Their Roles Toward Ligand-Receptor Interactions in Drug Discovery. 生物传感器检测类型及其在药物发现中配体-受体相互作用中的作用。

IF 1.8 4区医学

Assay and drug development technologies Pub Date : 2023-07-01 DOI: 10.1089/adt.2023.003

Garima Gupta, Kanupriya Jha, Sarika Chaudhary

{"title":"Biosensor Assays Types and Their Roles Toward Ligand-Receptor Interactions in Drug Discovery.","authors":"Garima Gupta, Kanupriya Jha, Sarika Chaudhary","doi":"10.1089/adt.2023.003","DOIUrl":"https://doi.org/10.1089/adt.2023.003","url":null,"abstract":"Ligand-receptor interactions (LRIs) are the basis for all the biological processes taking place in living cells and have been exploited to develop and implement in medical field a number of highly sensitive biosensors for the detection of various biomarkers in complex biological fluids. Drug-target interactions, one of the LRIs, are important to understand the biological processes that further help in developing new and better therapeutic molecules. Biosensors based on these interactions give us an idea for the need of modification of existing drugs or to develop new drugs. Common approach to develop biosensors requires the labeling; however, label-free systems provide advantages in avoiding the chances of conformational changes, off-site labeling, and labeling-based hindrances, thus saving time and effort toward assay development. Preliminary drug screening assays are carried out in two-dimensional (2D) models, followed by animal models, which require huge capital investment to reach from bench-top to clinical trials, where only 21% of new compounds make way to phase-1 clinical trials. Three-dimensional culture or organoid culture or organ-on-chip technology has made way for predictive and complex in vitro approach that recapitulates human physiology and represents more similar in vivo behavior than 2D. Multiplexing and nanotechnology have remarkably enhanced the efficacy of biosensors and might lead to a generation of miniaturized biosensors and more than just point-of-care kits. This review provides in-depth analysis of different types of biosensor assays based on drug-target interactions, their advantages, and limitations based on cost, sensitivity, and selectivity and industrial applications.","PeriodicalId":8586,"journal":{"name":"Assay and drug development technologies","volume":"21 5","pages":"190-201"},"PeriodicalIF":1.8,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9875938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

TWIST1 Promotes Colorectal Carcinoma Stemness and Oxaliplatin Resistance by Activating Microfibrillar-Associated Protein 2. TWIST1通过激活微纤维相关蛋白2促进结直肠癌干性和奥沙利铂耐药

IF 1.8 4区医学

Assay and drug development technologies Pub Date : 2023-07-01 DOI: 10.1089/adt.2022.099

Ying Liu, Minhan Chen, Bo Wu

{"title":"TWIST1 Promotes Colorectal Carcinoma Stemness and Oxaliplatin Resistance by Activating Microfibrillar-Associated Protein 2.","authors":"Ying Liu, Minhan Chen, Bo Wu","doi":"10.1089/adt.2022.099","DOIUrl":"https://doi.org/10.1089/adt.2022.099","url":null,"abstract":"Colorectal carcinoma (CRC) is a fatal disease and ranks as the third most prevalent cancer globally. Stemness and drug resistance are the main causes of tumor recurrence in CRC. This study attempted to probe the impact of TWIST1 on CRC stemness and resistance to oxaliplatin and to uncover the underlying regulatory mechanism of TWIST1. mRNA expression data from The Cancer Genome Atlas-CRC were subjected to differential analysis. The target gene in the study was determined according to literature citation. ChIPBase was utilized to predict likely targets downstream of the target gene. Pearson was employed for correlation analysis. Quantitative real-time polymerase chain reaction was used to assess TWIST1 and microfibrillar-associated protein 2 (MFAP2) levels in CRC and normal cells. The cell viability was assayed through cell counting kit-8 and IC50 value was calculated. Flow cytometry was applied to assay the cell apoptosis. Apoptosis assays were applied to evaluate cell apoptosis. CD44, CD133, SOX-2, ERCC1, GST-π, MRP, and P-gp protein expression levels were assayed by Western blot. The targeting relationship between TWIST1 and MFAP2 was ascertained through dual-luciferase and chromatin immunoprecipitation (ChIP). TWIST1 possessed high expression in CRC tissue and cells. TWIST1 knockdown strikingly promoted cell apoptosis and reduced cell stemness and cell resistance to oxaliplatin. Bioinformatics prediction suggested that MFAP2, which was overexpressed in CRC tissue and cells, was the target gene downstream of TWIST1. Dual-luciferase and ChIP assays validated that there was a targeting relationship between TWIST1 and MFAP2. The results of the rescue assay demonstrated that TWIST1 fostered CRC stemness and oxaliplatin resistance by activating MFAP2 expression. These outcomes implied that TWIST1 enhanced CRC stemness and oxaliplatin resistance by activating the transcription of MFAP2. Therefore, TWIST1/MFAP2 axis possibly indicated a mechanism for regulating tumor progression.","PeriodicalId":8586,"journal":{"name":"Assay and drug development technologies","volume":"21 5","pages":"202-211"},"PeriodicalIF":1.8,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9871250","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Design, Synthesis, Molecular Docking, and Biological Evaluation of Isatin-Based Fused Heterocycles As Epidermal Growth Factor Receptor Inhibitors. 基于isatin的融合杂环表皮生长因子受体抑制剂的设计、合成、分子对接和生物学评价。

IF 1.8 4区医学

Assay and drug development technologies Pub Date : 2023-07-01 DOI: 10.1089/adt.2022.120

Ankush Kumar, Bhupinder Kumar, Rohit Bhatia

{"title":"Design, Synthesis, Molecular Docking, and Biological Evaluation of Isatin-Based Fused Heterocycles As Epidermal Growth Factor Receptor Inhibitors.","authors":"Ankush Kumar, Bhupinder Kumar, Rohit Bhatia","doi":"10.1089/adt.2022.120","DOIUrl":"https://doi.org/10.1089/adt.2022.120","url":null,"abstract":"A series of isatin-based fused heterocycles were designed, synthesized, and evaluated for anticancer activity against four cancer cell lines: MCF-7, MDA-MB-231, A549, and HL-60. Among them, Q3 and T4 were found to be potent anticancer agents. Furthermore, two compounds Q3 and T4 were selected for epidermal growth factor receptor (EGFR) inhibitory activity. Two compounds Q3 and T4 were found to be most potent EGFR inhibitors with IC50 of 0.22 ± 0.10 and 0.19 ± 0.07 μM. The EGFR inhibitory activity of standard drug erlotinib was 0.08 ± 0.02 μM. Structural Activity Relationship studies showed that electronegative atoms were necessary for EGFR inhibitory potential. Finally, molecular docking studies were carried out to check the binding pattern of synthesized derivatives with the adenosine triphosphate (ATP) binding site of EGFR and results revealed that compounds Q3 (-9.2 kcal/mol) and T4 (-8.9 kcal/mol) exhibited better binding affinity than reference drug erlotinib (-7.3 kcal/mol).","PeriodicalId":8586,"journal":{"name":"Assay and drug development technologies","volume":"21 5","pages":"222-233"},"PeriodicalIF":1.8,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10250656","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0