ADMET and DMPK最新文献

Background and purpose: Cancer represents a major challenge to public health; therefore, identifying doxorubicin hydrochloride (DOX·HCl) as an important chemotherapy drug holds considerable significance.

Experimental approach: An electrochemical sensing strategy was designed for DOX·HCl determination by using Y-Co bimetallic metal-organic framework (Y-Co MOF) modified carbon paste electrode (CPE). The Y-Co-MOF was successfully prepared via the solvothermal method.

Key results: Characterizations using field emission scanning electron microscopy, transmission electron microscopy, X-ray diffraction, Fourier transform infrared spectroscopy and energy-dispersive X-ray spectroscopy with elemental mapping images were used to evaluate the morphological features, crystalline structure, functional groups, and elemental composition of the Y-Co-MOF. From cyclic voltammetric studies, well-defined redox peaks of DOX·HCl with improved response peak currents at lower overpotentials were observed on the surface of Y-Co MOF/CPE compared to the unmodified CPE. This indicated that the as-prepared modified CPE has a strong and efficient redox capability toward DOX·HCl. Under the optimized parameters and conditions, the linear response range from differential pulse voltammetry measurements for DOX·HCl were 0.0025 to 100.0 μM, with a low limit of detection of 0.001 μM. Finally, the ability of the designed sensing platform to determine the amounts of DOX·HCl in the injection sample was studied and it has been observed a high and efficient ability with satisfactory values of recovery and relative standard deviation.

Conclusion: This analytical approach offers a useful means for the analysis of pharmaceutical formulations, providing potential advantages in cancer therapy.

Background and purpose: Chloramphenicol (CAP) is a broad-spectrum antibiotic whose unregulated presence in pharmaceuticals and food products raises significant health concerns, underscoring the need for rapid, reliable detection methods. This study aimed to develop a sensitive and economical electrochemical sensing platform based on a novel gadolinium tungstate (Gd₂(WO₄)₃) and sulphur-doped graphitic carbon nitride (S-g-C₃N₄) nanocomposite for the efficient determination of CAP.

Experimental approach: The Gd₂(WO₄)₃/S-g-C₃N₄ nanocomposite was synthesized via a simple co-precipitation method and characterized using XRD, XPS, EDS, and TEM to confirm structural and morphological integration. A glassy carbon electrode modified with the composite was evaluated by cyclic and linear sweep voltammetry, along with analyses of interference, repeatability, stability, and real samples in eye-drop formulations and milk.

Key results: The modified electrode exhibited significantly enhanced electrocatalytic oxidation of CAP compared with bare and individually modified electrodes, demonstrating high sensitivity, good selectivity against common interferents, and strong operational stability and reproducibility. A low detection limit was achieved, and the electrode effectively quantified CAP in real matrices with satisfactory recovery.

Conclusion: The findings establish the Gd₂(WO₄)₃/S-g-C₃N₄ nanocomposite as an efficient sensing material, offering a reliable, stable, and cost-effective platform for routine monitoring of antibiotic residues. While minor optimization may further expand its applicability, the study advances electrochemical sensing by introducing a robust nanocomposite with improved analytical performance for CAP detection.

Background and purpose: The precise quantification and quality evaluation of glycopyrronium bromide (GLB), a long-acting muscarinic antagonist widely used in the treatment of chronic obstructive pulmonary disease, requires the development of advanced analytical methodologies capable of achieving high sensitivity, accuracy, and selectivity to ensure therapeutic efficacy and formulation integrity. This study aims to overcome the limitations of conventional methods by developing a rapid, cost-effective method for determining GLB.

Experimental approach: To achieve this, titanium dioxide nanoparticles (TiO₂ NPs) were initially applied onto a glassy carbon electrode surface to provide an enhanced surface area and increased conductivity. Subsequently, a TiO₂ nanoparticle-supported molecularly imprinted polymer (MIP) film was synthesized via photopolymerization using GLB as the template molecule, 4-amminobenzoic acid (4-ABA) as the functional monomer, ethylene glycol dimethacrylate as the crosslinking agent, and 2-hydroxyethyl methacrylate (HEMA) as the basic monomer.

Key results: The optimized GLB/4-ABA@TiO₂ NPs/MIP- sensor demonstrated outstanding analytical performance, achieving ultra-low picomolar detection limits. The system exhibited superior selectivity (confirmed by high imprinting factor), excellent repeatability and reproducibility, and satisfactory stability. It was successfully applied to the accurate measurement of GLB in both commercial serum and pharmaceutical formulations.

Conclusion: The designed nanomaterial-embedded MIP-based electrochemical system presented here offers a highly successful, sensitive, and selective method for GLB determination. The work significantly advances knowledge in the field of analytical medicine and drug monitoring by providing a fast, robust alternative for routine clinical and quality-control tracking of GLB.

Background and purpose: As a classic β-blocker with low systemic clearance, metoprolol has been linked to rare but clinically significant hepatotoxicity, yet its hepatic metabolic fate remains poorly characterized.

Experimental approach: Metoprolol was incubated individually in plateable human and animal hepatocytes, and recombinant cytochrome (CYP) P450 enzymes, followed by sample processing for cytotoxicity assessment, stability analysis, phenotyping and metabolite identification studies.

Key results: In vitro cytotoxicity assessment revealed distinct species-specific responses to metoprolol exposure. Metoprolol showed no observable cytotoxicity across the tested concentration range (0 to 500 μM) in human hepatocytes, whereas it was cytotoxic only at a concentration of 500 μM in rat hepatocytes. Metabolic characterization showed low intrinsic clearance in human hepatocytes (0.56±0.12 μL min^-1 per million cells) over a 72-hour incubation. Comprehensive mass spectrometer analysis identified 22 metabolites across four species (rat, dog, monkey, and human) and fifteen metabolites were identified as the new ones, with CYP2D6-mediated biotransformation pathways (including mono-oxygenation, O-demethylation, and oxidation) accounting for the generation of four major metabolites (M1, M10, M13, M17). Notably, species-specific metabolism was observed for s-hydroxy-metoprolol (M10). It served as the predominant metabolite in rat hepatocytes and underwent subsequent bioactivation to a reactive glutathione (GSH) conjugate. Inhibition studies with 1-aminobenzotriazole (a non-specific CYP inhibitor) confirmed the CYP-dependent nature of this hepatotoxic metabolic pathway.

Conclusion: The sustained metabolic activity of plateable hepatocytes facilitated a comprehensive metabolic profiling of metoprolol, including direct observation of GSH-mediated bioactivation. Integrating with cytotoxicity data, these findings offered crucial insights into its hepatic adverse effects.

Background and purpose: Cancer remains a leading cause of death globally, with long-term treatment success hindered by metastasis, recurrence, and therapy resistance. A central driver of these limitations is cancer stem cells (CSCs) - a rare subpopulation of tumour cells endowed with self-renewal and differentiation potential. CSCs contribute critically to tumour progression, metastatic spread, and resistance to conventional therapies, yet no clinically validated strategies currently exist to accurately detect or selectively eliminate them.

Review approach: The paper systematically examined the literature on CSC origin, phenotypic characterization, isolation techniques, and mechanisms underlying resistance, including dormancy, enhanced DNA repair, apoptosis evasion, and microenvironmental protection. Particular attention was given to recent advances in nanomaterial-based strategies - metallic, carbon, and organic nanocarriers, designed to improve CSC-specific drug delivery, reactive oxygen species generation, pathway inhibition, and modulation of the CSC niche.

Key results: Current CSC markers and in vivo models remain ambiguous and poorly standardized, limiting translational progress. Nanotechnology provides promising solutions by enabling targeted delivery and multi-functional therapy integration, yet most systems are still at the preclinical stage, constrained by issues of biocompatibility, targeting precision, and manufacturing scalability.

Conclusion: Multifunctional nanoplatforms hold substantial potential to overcome CSC-driven resistance, improve therapeutic selectivity, and reduce recurrence. However, rigorous optimization and clinical validation are essential before these technologies can be integrated into routine oncology. This review advances understanding by outlining the intersection of CSC biology and nanomedicine, emphasizing translational pathways for CSC-targeted cancer therapy.

Background and purpose: Dopamine, 3,4-dihydroxyphenylalanine, functions as a catecholamine neurotransmitter in the brain, sending messages to other neurons to regulate information transmission to other areas of the brain, govern movement, and alter brain activity. Tyrosine undergoes an enzymatic process in the pharmaceutical industry to produce dopamine. Thus, it is crucial to measure both tyrosine and dopamine in bodily fluids simultaneously.

Experimental approach: In this work, we demonstrate the production of ZnO nanoparticles using a straightforward solvothermal technique. A straightforward, quick, and sensitive electrochemical sensing platform for dopamine detection was then created using the produced ZnO nanoparticles.

Key results: Cyclic voltammetry comparison revealed that the ZnO/carbon paste electrode considerably enhanced the dopamine oxidation process compared to the unmodified carbon paste electrode (CPE). With a low detection limit of 0.003 μM, the ZnO/CPE sensor's linear response for voltammetric dopamine determination was found to be between 0.01 and 480.0 μM.

Conclusion: The modified CPE effectively demonstrates its great accuracy in tyrosine-induced dopamine detection.

Background and purpose: The delivery of therapeutics to the central nervous system (CNS) remains a major challenge due to the restrictive nature of the blood-brain barrier (BBB), a key evolutionary feature that preserves brain homeostasis. This review seeks to synthesize current knowledge on BBB composition, physiology, and transport mechanisms, and critically analyses drug delivery strategies aimed at overcoming this barrier and enabling effective CNS therapies.

Approach: We conducted a comprehensive narrative review integrating evidence on BBB anatomy, transport and permeability mechanisms, drug delivery optimization strategies, with a particular focus on nanotechnology-based systems, and preclinical evaluation models.

Key results: We highlight how a deeper understanding of BBB architecture and dynamic regulation can inform rational design of targeted strategies. Drug delivery approaches are summarized and compared, with emphasis on the potential of nanotechnology-based platforms to enhance CNS drug delivery. Translational considerations, including scalability, reproducibility, and regulatory requirements, are critically addressed. Major challenges identified include receptor saturation, competition with endogenous ligands, disease-specific variability in BBB permeability, and the limited predictive value of current preclinical models. Emerging tools, such as organ-on-chip (for evaluation) and microfluidic mixing (for manufacturing nanomaterials), offer promising means to improve physiological relevance and accelerate translation.

Conclusion: Progress in BBB research has laid the groundwork for innovative therapies, but significant hurdles remain. Advancing CNS drug delivery will require collaborative work refining transport-targeting mechanisms, developing standardized preclinical models, and integrating fundamental research, applied nanomedicine, and regulatory science to open new opportunities for treating neurological and psychiatric disorders and brain tumours.

Background and objective: Pembrolizumab has shown significant therapeutic benefit in advanced non-small cell lung cancer (NSCLC), but it remains uncertain which patients will benefit the most, and recent data suggest that programmed death-ligand 1 (PD-L1) expression as a single predictive biomarker is insufficient. This systematic review and meta-analysis looked at the safety and efficacy of pembrolizumab in PD-L1-positive advanced NSCLC patients, with a particular focus on disparities in treatment response to PD-L1 level of expression and demographic characteristics.

Method: According to the PRISMA 2020 guidelines, six large databases were searched up to March 2025 for randomized controlled trials comparing pembrolizumab with chemotherapy in patients with such conditions. Overall survival (OS) and progression-free survival (PFS) were chosen as primary outcomes, and overall response rate (ORR) and safety profiles as secondary endpoints. A meta-analysis was conducted using a random-effects model, and the Cochrane risk of bias (ROB2) tool was employed to evaluate study quality. Seven randomized controlled trials involving 4,900 patients were included in the analysis.

Key results: Pembrolizumab had a substantially better performance compared to chemotherapy for all the measures of efficacy: OS (hazard ratio (HR) 0.65, 95 % confidence interval (CI): 0.57 to 0.73, P < 0.00001), PFS (HR 0.55, 95 % CI: 0.42 to 0.72, P < 0.0001) and ORR (relative risk 2.10, 95 % CI: 1.51 to 2.93, P < 0.0001). Subgroup analysis showed greater survival benefit in patients younger than 65 years (OS HR 0.55) compared to patients aged 65 and older (OS HR 0.72), and in females (OS HR 0.44) compared to males (OS HR 0.67). Of most significant importance, those with PD-L1 expression <1 % also saw considerable benefit in survival (OS HR 0.60), casting doubts over the existing biomarker-based selection criteria.

Conclusion: In conclusion, pembrolizumab achieves clinically meaningful survival benefits and an acceptable toxicity in PD-L1-positive advanced NSCLC. The high efficacy observed even in low PD-L1 expressers, and demographic differences in drug response, suggest that existing patient selection criteria could potentially be extended. These findings justify the application of a more advanced approach involving multiple biomarkers for more precise treatment allocation.

Background and purpose: Research on the detection of uric acid (URA) and dopamine (DPA) is ongoing because of the difficulties posed by their closely overlapping oxidation potentials. Tungsten disulfide nanostructures have become attractive electrode materials to address this problem due to their low toxicity, low cost, easy production, and strong catalytic activity.

Experimental approach: For voltammetric detection of compounds, we present the creation of an electrochemical sensor based on a glassy carbon electrode modified with tungsten disulfide nanostructures.

Key results: According to electrochemical analyses, the manufactured sensor performed exceptionally well, having a broad LDR of 0.03 to 600.0 μM and a low LOD of 10 nM for DPA.

Conclusion: The effective detection of compounds in real samples, such as injections and urine, with acceptable recovery rates further confirmed the suggested sensor's practical usefulness. In addition to offering a viable method for creating tungsten disulfide-based modified electrodes, this study holds promise for future applications in bioanalytical sensing and clinical diagnostics.

Background and purpose: Monitoring antibiotic drugs in the environment is particularly relevant given their role in fostering microbial resistance, impacting aquatic species and human health. Therefore, this work addresses the lack of a sustainable and cost-effective analytical approach and reports the development of a competitive electrochemical immunosensor for the rapid analysis of trimethoprim (TMP), an aquatic contaminant of emerging concern, overcoming the limitations of conventional methods that are often costly and time-consuming.

Experimental approach: A miniaturized 3-electrode system was developed to support the analyses of a low-volume sample (200 μL), using a low-cost carbon-paper working electrode, pencil graphite lead auxiliary electrode and a stainless-steel needle reference electrode. Scanning electron microscopy was used to characterize the transducer, revealing a network of randomly arranged carbon fibres, significant for efficient antibody immobilization. For the immunoassay construction, an anti-TMP antibody was physically adsorbed to a small-sized transducer (d = 4 mm) for the specific recognition of TMP, followed by incubation with the enzyme-conjugate (horseradish peroxidase) and the enzyme-substrate (tetramethylbenzidine).

Key results: The analytical signal was recorded by chronoamperometry (1-minute reaction) and yielded a limit of detection of 34 ng L^-1. The 45-minute assay demonstrates accuracy (92.0 to 103.2 % in fishery species including codfish, mackerel, crab, and hake), reproducibility (6.1 and 9.3 % for repeatability and inter-day variation coefficient) and high selectivity (bias less than 5 %) analysis. The sensor's performance was validated against a conventional Enzyme-Linked Immunosorbent Assay.

Conclusion: This study introduces a sustainable electrochemical immunosensor, offering a portable and eco-friendly alternative for the rapid detection of TMP in fishery species, addressing the limitations of traditional methods.