Assay and drug development technologies最新文献

Naotai formula (NTF) is clinically used for stroke treatment, yet its molecular mechanisms involving vascular and metabolic regulation remain unclear. This study combines network pharmacology (NP) and Mendelian randomization to explore NTF's therapeutic targets and pathways in stroke. Stroke-related genes were sourced from public databases, and NTF's active compounds were screened using SwissADME. Summary-data-based Mendelian randomization (SMR) analysis, combined with colocalization, integrated stroke genome-wide association study data with blood expression quantitative trait loci and protein quantitative trait loci datasets to identify genes/proteins causally linked to stroke risk. Protein-protein interaction (PPI) network and drug-compound-target networks were constructed using Cytoscape and R. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses identified functional roles. Molecular docking assessed interactions between key compounds and prioritized targets. A total of 579 overlapping genes linked NTF and stroke. SMR identified 44 stroke-associated genes, with vascular endothelial growth factor A, angiotensinogen (AGT), and lipoprotein(a) replicated. Validation in Brain-eMeta supported eight of these targets, supporting tissue relevance. Enrichment analyses highlighted pathways including PPAR signaling, cholesterol metabolism, and vascular function. Core targets (Adiponectin, C1Q and collagen domain containing (ADIPOQ), Scavenger Receptor Class B Member 1 (SCARB1), and AGT) emerged from PPI networks. Molecular docking confirmed strong binding between NTF's Calycosin and AGT, a key renin-angiotensin system protein. NTF likely mitigates stroke by modulating genes involved in cholesterol metabolism and vascular regulation. The predicted Calycosin-AGT interaction provides a genetically informed hypothesis for a possible role in renin-angiotensin modulation. This integrative approach provides genetic and mechanistic insights into NTF's therapeutic efficacy.

Automation plays a crucial role in enhancing efficiency and increasing capacity for in vitro absorption, distribution, metabolism, and excretion profiling in early drug discovery. Building an automation platform requires a careful balance of innovation and practical considerations to align assay needs with technological capabilities. In this study, we present a state-of-the-art automation system designed to support the miniaturization of the Caco-2 permeability assay from the 24-well to the 96-well format. This platform integrates advanced infrastructure for cell culture and assay execution, along with several key features, including innovative cleaning protocols, cutting-edge plate tracking, and dynamic scheduling capabilities. The fully automated 96-well platform delivers significant efficiency gains, increased capacity, and faster turnaround for permeability assay support while maintaining high predictive accuracy. It correctly classified 94% of 50 literature compounds, demonstrating strong concordance with the established 24-well format. Moreover, the platform enables large-scale permeability data generation, advancing our "predict-first" modeling paradigm, in which predictive models guide experimental design and compound prioritization.

Rheumatoid arthritis (RA) is a chronic inflammatory disease whose exact etiology is yet unidentified. Dexamethasone sodium phosphate (DSP) is an established anti-inflammatory agent, but its application is limited due to its dose-dependent toxicity. This can be minimized by targeting the delivery of DSP. Zinc oxide nanoparticles (ZnONPs) have potential in the management of RA owing to their anti-inflammatory and antioxidant characteristics. The aims of this research were to develop, optimize, and determine the cytotoxicity of FA decorated DSP loaded ZnONPs. The biogenic ZnONPs have been synthesized using Piper nigrum. The Zeta potential, particle size, PDI, and loading ability of DSP-Pn@ZnONPs were improved utilizing Box-Behnken design since these factors are crucial in preserving the pharmacokinetic behavior of nanoparticles. The FA-DSP-Pn@ZnONPs were characterized via UV-visible spectrophotometer, X-ray diffraction, energy dispersive spectrophotometer, scanning electron microscopy, TEM, FT-IR, Zeta analysis and H¹NMR. Nanoparticles exhibited minimal DSP release at 32.7207% at 7.4 pH (normal blood), but a substantial release of 88.72544% at 6.5 pH (RA synovial site) indicating its potential for targeting ability at the inflammatory site. Moreover, the various in vitro analyses include antioxidants, and anti-inflammatory. Furthermore, the release of FA-DSP-Pn@ZnONPs was accurately described by the Korsmeyer-Peppas model and exhibited a non-Fickian process, which was governed by both diffusion and erosion. The cytotoxicity ability and anti-inflammatory effects of NPs were determined using the MTT analysis method in non-lipopolysaccharide (LPS) and LPS-activated RAW 264.7. The FA-DSP-Pn@ZnONPs showed significant anti-inflammatory and anti-arthritis activities. At the highest concentration, it inhibited cell hemolysis and growth of the LPS-stimulated macrophage cell line, suggesting potential therapeutic interventions against RA.

This review examines the drug-like, cancer-suppressing, and food-based properties of paclitaxel, naringenin, and quercetin while emphasizing their therapeutic pathways and molecular functions. The chemotherapeutic agent paclitaxel stabilizes microtubules for cell cycle arrest, and naringenin alongside quercetin shows strong anticancer responses, antioxidant effects, and anti-inflammatory actions. The review explains how these compounds serve in cancer treatment together with their pharmacological mechanisms and it describes how novel drug delivery systems boost their therapeutic potential and bioavailability. Drug-testing evidence as well as patent documentation reveals increasing attention toward these drug compounds in cancer treatment. The three compounds paclitaxel, naringenin, and quercetin show great potential as cancer treatment and prevention agents while researchers continue to develop their clinical performance advanced through ongoing studies.

While sodium-glucose transporter 2 inhibitors (SGLT2i) demonstrate urate-lowering effects, their causal role in Gout prevention remains controversial. This study employs advanced Mendelian randomization (MR) techniques to dissect immune-mediated mechanisms underlying this relationship. Using bidirectional two-sample MR and mediation analysis, we analyzed genetic instrument variables for SGLT2i (10 single-nucleotide polymorphisms, F-statistic >20), Gout risk (6,810 cases/477,788 controls), and 731 immune cell phenotypes. Pleiotropy and heterogeneity were also assessed to ensure robustness. The study confirmed a significant indirect effect of SGLT2i, which exhibited a 2.6% reduced Gout risk (Odds Ratio [OR]: 0.9738, 95% confidence interval [CI] = 0.9623, 0.9854, P = 1.12e-05). Thirty-five immune cell phenotypes were identified as significantly affecting Gout development, with key phenotypes such as CD86 on myeloid Dendritic cell (DC) (OR: 0.9966; 95% CI = 0.9930, 0.9995), contributing to 12.8% of the overall mediation effect. No evidence of heterogeneity or pleiotropy was detected and reverse-direction MR corroborated these findings. Our study first established SGLT2i as Gout-protective agents through DC-mediated immunomodulation, offering mechanistic insights for targeted prevention strategies in clinical practice.

Migraine is a debilitating neuromuscular disorder marked by severe, one-sided headaches. Triptans, such as Zolmitriptan (ZMP), act as serotonin receptor agonists and are commonly used in migraine treatment. However, ZMP, classified under Bio-pharmaceutics Classification System Class III, suffers from low oral bioavailability (<4%), limiting its therapeutic efficacy. To address this, intranasal delivery using nanostructured lipid carriers (NLCs) has emerged as a promising strategy to enhance bioavailability and enable targeted brain delivery. The study aimed to improve the bioavailability of ZMP by developing intranasal NLCs and evaluating their potential for targeted brain delivery in migraine treatment. ZMP-loaded NLCs (ZMP-NLCs) were formulated using the hot melt emulsification method with high-speed stirring. The NLCs were optimized based on particle size, zeta potential, entrapment efficiency (EE), and drug release over 8 h. The optimized formulation consisted of 1% Glycerol Monostearate (solid lipid), 1% Capmul MCM (liquid lipid), and 1.5% Tween 80 (surfactant). The NLCs were characterized using Fourier transmission infrared (FTIR) spectroscopy, powder X-ray diffraction (XRD), and scanning electron microscopy (SEM) to confirm drug incorporation and particle morphology. Pharmacodynamic studies were conducted to assess brain delivery and antimigraine efficacy. The optimized NLC formulation exhibited a particle size of 233 ± 9.07 nm, a polydispersity index of 0.257 ± 0.03, a zeta potential of -42.8 ± 0.5 mV, an EE of 89.35 ± 0.9%, and a drug release of 87.1 ± 1.03% after 8 h. FTIR and XRD analyses confirmed the successful incorporation of ZMP into the NLCs without significant chemical interactions. SEM revealed uniform, spherical particles. Pharmacodynamic studies demonstrated effective brain delivery of ZMP, bypassing the blood-brain barrier, and significantly enhancing its antimigraine potential. This study highlights the potential of ZMP-NLCs for intranasal delivery. NLCs offer improved bioavailability and targeted brain therapy for effective migraine management. The findings suggest that NLCs are a promising approach for enhancing the therapeutic efficacy of ZMP.

Diclofenac sodium (DS) is categorized under the nonsteroidal anti-inflammatory class of drugs that also belongs to biopharmaceutical classification system (BCS) class II. It has limited dissolution parameters which also resist the total bioavailability but it has a good transdermal permeability characteristic and the pharmacokinetic parameters of DS make it suitable for the formulation of nanostructured-lipid carrier (NLC)-based gel transdermal delivery. The research aimed to design and develop a drug-delivery system (DDS), i.e., DS-NLCs incorporated in gel to modulate its anti-inflammatory action via skin. The formulation was optimized using Taguchi's approach and the resultant NLCs were thoroughly characterized, including assessments for zeta potential, particle size, and morphological evaluation. Furthermore, particular investigations were carried out for DS-NLCs, including drug encapsulation efficiency, ex vivo release properties in Phosphate Buffer Saline at pH 7.4, and an in vivo skin irritation test. DS-NLCs had a mean size of 339 ± 25 nm and were spherical-shaped particles. With an encapsulation effectiveness of 84%, the NLCs were found to have effectively loaded drugs. Moreover, these NLCs demonstrated a sustained release characteristic that persisted for a maximum of 24 h, suggesting their potential for gradual and regulated drug release. Lipid components demonstrated good stability over 90 days and were biocompatible with the DS. Furthermore, compared with the usual formulation, topical gel loaded with NLC (GNLC) containing DS considerably suppresses edema in the in vivo result, suggesting that the developed formulation has superior anti-inflammatory efficacy. These NLCs provide prolonged release and better drug solubility, both of which boost therapeutic outcomes and control the drug's anti-inflammatory potential. The study's conclusion emphasizes DS-NLC's potential as a cutting edge and effective medication delivery technology. The results indicate the need for more preclinical research, which presents an effective direction for developing a more potent and well-tolerated therapeutic strategy.

The emergence of multidrug-resistant bacteria has led to an urgent need for novel antimicrobial agents. Antimicrobial peptides (AMPs) exhibit broad-spectrum and highly effective antibacterial activity and are less prone to resistance, making them potential candidates for the next generation of antimicrobial drugs. However, screening for AMPs from a vast library of peptides through wet lab experiments is a slow and laborious process. By leveraging large datasets of labeled peptides, researchers utilize deep learning algorithms to train models that capture complex patterns and features associated with antimicrobial activity, which advance the discovery and development of novel AMPs. Since the discovery of certain lengths of AMPs has been rarely reported, we applied deep learning to accelerate the discovery of AMPs consisting of 15 amino acids and developed a model named AMPPRED15 in this article. Wet lab experiments were also conducted to evaluate the performance of the model. Fortunately, we successfully identified two AMPs, one of which demonstrated antibacterial activities comparable to the marketed antibiotic cefoperazone sodium.

The neoteric advancement in nanotechnology accompanied the development of targeted drug delivery system. The utmost muddle facing the investigators is targeted drug delivery to specific sites. The unfolding of a new nanoparticle carrier called nanosponges should label these problems. The finding out of nanosponges has become a significant step in overcoming certain problems essentially as drug toxicity; impoverish drug's availability and release of drug in a foreseeable fashion as they can take in both hydrophilic and hydrophobic drug. Nanosponges constitute a porous structure in nature that has the sole ability to entrap the drug moieties and offers merit of desired release. Nanosponges are mini sponges that can circulate in the body to make it to the specific site and cohere on the surface to release the drug in a controlled and predictable manner. Similarly, afresh invented medications have been come across to poorly water-soluble drug, which may be applicable in resolving the solubility problem by nanocrystallization via nanocrystals. This review will cover nanosponges and nanocrystals, as well as the diverse methodologies employed in their formulation, characterization, and their applications. The study also throws light on medically authorized nanosponges and nanocrystals, including those already developed that can elicit a significant outcome helpful in clinical studies as well as used by various research workers for their upcoming studies.