Assay and drug development technologies最新文献

Lacidipine, a calcium channel antagonist, is primarily used to treat hypertension. It is classified as a Biopharmaceutics Classification System Class II drug and exhibits an oral bioavailability of 10% due to its extensive hepatic first-pass metabolism. This research study focused on formulating lacidipine-loaded cubosomal nanovesicles developed into rapidly dissolving oral films as an alternative to overcome the downsides faced by conventional antihypertensive therapy. Lacidipine-loaded cubosomes were prepared utilizing a top-down technique using lipid and surfactant and were further developed into fast dissolving oral films. Box-Behnken design was used for the optimization of process variables to achieve minimum particle size and greater entrapment efficiency of the nanovesicles, and response data were statistically evaluated. The optimized cubosomal dispersions upon characterization reported particle size within nanorange (116.8-341 nm) and an entrapment efficiency of 88.15%-97.1%, with 91.72% of total drug content. Morphological studies revealed uniformly dispersed vesicles with cubic to spherical shape. Oral rapidly dissolving films, after evaluation, were reported to have transparent to opaque appearance with a highly porous nature, which was confirmed by scanning electron microscopic imaging and displayed uniformity in weight and thickness and reported optimum mechanical strength and considerable flexibility, with disintegration time of 37.67 ± 3.68 s and exhibited 91.44% ± 1.65% in vitro drug release after 6 min. Short-term stability studies conducted on films at 25°C ± 2°C and 60% ± 5% relative humidity for 3 months demonstrated no significant variation in morphological and mechanical properties. Therefore, lacidipine-loaded cubosomal rapid dissolving oral films may be a promising formulation approach for the management of hypertension.

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.

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.

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.

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.

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.