ADMET & DMPK (ISSN 1848-7718) is an international, peer reviewed open-access Journal aiming for rapid dissemination of original research articles, review papers and comments in the broad areas of absorption, distribution, metabolism, excretion, toxicology and pharmacokinetics of drugs. The emphasis is on rapid publishing of articles of high scientific quality to make them freely available to researchers worldwide.
Elucidating CYP2D6-driven metabolism and hepatotoxic bioactivation of metoprolol in plateable human and animal hepatocytes
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 a-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.
Copyright (c) 2025 Jiang Pu, Mei Yang, Min Zhang, Ruiqi Gao, Yue Xiao, Lingyu Liu, Chuanjing Zhang, Wennuo Xu, Kaifang Li, Wanyong Feng https://creativecommons.org/licenses/by/4.0
Nano-biomaterials in cancer therapy: Advances in targeting and overcoming cancer stem cell resistance
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. .
Copyright (c) 2025 Marzieh Dehghani, Behnam Hajipour-Verdom, Fatemeh Rahimzadeh, Parviz Abdolmaleki https://creativecommons.org/licenses/by/4.0
ZnO-modified carbon paste electrode for electrochemical sensing of dopamine in the presence of tyrosine
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.
SI: Electrochemistry in Drug Discovery and Development
Copyright (c) 2025 Ali Obaid Imarah, Nada Hasan, Mustafa G. Alabbasi https://creativecommons.org/licenses/by/4.0
Advancing through the blood-brain barrier: mechanisms, challenges and drug delivery strategies
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.
Copyright (c) 2025 Ronny Vargas, Noelia Martinez-Martinez, Catalina Lizano-Barrantes, Jorge Andrés Pacheco-Molina, Encarna García-Montoya, María Pilar Pérez-Lozano, Josep María Suñe-Negre, Carlos Suñe, Marc Suñe-Pou https://creativecommons.org/licenses/by/4.0
Epithelial-mesenchymal dynamics in cancer: Role of signalling pathways, stromal interactions and natural therapies
Background and purpose: Epithelial-mesenchymal transition (EMT) and its reverse process, mesenchymal-epithelial transition (MET), play crucial roles in embryogenesis, tissue regeneration, and cancer progression. Dys­regulation of EMT/MET pathways in cancer contributes to metastasis and drug resistance. Approach: This review discusses the signalling pathways that are correlated with EMT in cancer and investigates the therapeutic potential of naturally occurring compounds in modulating these processes. The intricate relationship between stromal cells, drug resistance, and EMT is discussed, highlighting the emerging role of MET in stabilizing distant metastasis. Additionally, the impact of p53 on EMT and its implications in cancer metastasis are discussed. The review also provides an overview of therapeutic molecules, both plant- and animal-derived, that regulate EMT, highlighting their potential in cancer treatment. Specifically, plant-based compounds from Atractylodes lancea, Dendrobium officinale, Panax ginseng and Platycodon grandiflorus, as well as animal-derived substances like bee venom and snake venom, are highlighted. Furthermore, marine-based compounds, including caprolactin C, laminaran sulfate, BFP-3, bryostatin 1, sinulariolide, manzamines, halichondrin B, eribulin and biemamides, exhibit significant anti-metastatic effects by targeting EMT-associated pathways. Conclusion: The diverse range of therapeutic molecules discussed in this review provides promising therapeutic avenues for developing targeted strategies against EMT in cancer.
Copyright (c) 2025 Siddharth Singh, Iram Khan, Anindita Behera, Kamesh R Babu, Faisal Rehman, Farah Rehan, Shraddha Manish Gupta https://creativecommons.org/licenses/by/4.0
Pembrolizumab in PD-L1-positive Advanced Non-Small Cell Lung Carcinoma: A Meta-Analysis Survival Benefits and Immune-related Toxicity Events Patterns
Pembrolizumab has shown substantial therapeutic advantages in advanced non-small cell lung cancer (NSCLC); however, identifying which patients will benefit most remains difficult, and recent studies suggest that PD-L1 expression alone may not be a sufficient predictive biomarker. This systematic review and meta-analysis investigated the effectiveness and safety of pembrolizumab in advanced NSCLC patients with PD-L1 positivity, with particular attention to variations in treatment response according to PD-L1 expression levels and demographic characteristics. Adhering to the PRISMA 2020 guidelines, a comprehensive search of six major databases was conducted up to March 2025 for randomized controlled trials that compared pembrolizumab with chemotherapy in this patient population. Overall survival (OS) and progression-free survival (PFS) were designated as primary endpoints, while objective response rate (ORR) and safety profiles were assessed as secondary outcomes. A random-effects model was used for meta-analysis, and study quality was evaluated with the Cochrane ROB2 tool. The analysis incorporated seven randomized controlled trials encompassing 4,900 participants. Pembrolizumab consistently outperformed chemotherapy across all efficacy endpoints: OS (HR 0.65, 95% CI: 0.57–0.73, P < 0.00001), PFS (HR 0.55, 95% CI: 0.42–0.72, P < 0.0001), and ORR (RR 2.10, 95% CI: 1.51–2.93, P < 0.0001). Subgroup analyses indicated greater survival benefits in patients under 65 years of age (OS HR 0.55) compared to those 65 or older (OS HR 0.72), and in female patients (OS HR 0.44) relative to males (OS HR 0.67). Importantly, individuals with PD-L1 expression below 1% also showed significant improvement in survival (OS HR 0.60), raising questions about the existing biomarker-based selection criteria. In conclusion, pembrolizumab offers meaningful survival benefits and a acceptable safety profile in PD-L1-positive advanced NSCLC. The notable efficacy observed even in patients with low PD-L1 expression, along with demographic variations in treatment response, suggests that current patient selection criteria may require expansion. These findings advocate for a more nuanced approach incorporating multiple biomarkers to optimize treatment allocation. (PROSPERO ID: CRD420251023017).
Copyright (c) 2025 Alendra Chakramurty, Adetya Rahma Dinni, Ihda Silvia, Aprilyan Laras Cantika, Citrawati Dyah Kencono Wungu https://creativecommons.org/licenses/by/4.0
Efficient electrochemical determination of dopamine in the presence of uric acid in real samples using tungsten disulfide nanostructure modified electrode
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.
Copyright (c) 2025 Ibrahim Ayad Jihad, Thekrayat Joodi Jassim, Zainab Naeif Mageed https://creativecommons.org/licenses/by/4.0
Development of a carbon paper-based electrochemical immunosensor for trimethoprim detection in fishery species: monitoring antibiotic contaminants
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.
Copyright (c) 2025 Maria Freitas, Vitória Dibo, Rita Ribeiro, Cristina Delerue-Matos, Simone Morais, Álvaro Torrinha https://creativecommons.org/licenses/by/4.0
Electrochemical sensing and quantification of theobromine in cocoa products at polyvaline functionalized graphite paste sensor electrode
Background and purpose: Theobromine (THB), an alkaloid present in various plants, is widely used in pharmaceutical formulations and food products. Increased consumption leads to health risks in both humans and animals. Experimental approach: An electrochemically polymerized polyvaline-modified graphite paste sensor (PVMGPS) was developed in this work to investigate the mechanistic and kinetic pathways of the electrooxidation of THB. Electrochemical impedance spectroscopy and scanning electron microscopy were used for characterizing the designed sensors. The fabricated PVMGPS under optimal conditions produced enhanced current responses compared to the bare graphite paste sensor (BGPS). Multiple parameters were investigated using cyclic voltammetry and differential pulse voltammetry. Key results: The electroactive surface areas of the BGPS and PVMGPS were evaluated as 0.025 and 0.252 cm2, respectively. The study of the effect of pH of phosphate buffer solution (PBS) and further analysis revealed that the electro-oxidation involves equivalent numbers of electrons and protons. Scan rate dependence revealed that the oxidation of THB proceeds through diffusion-controlled kinetics. The limit of detection and limit of quantification were evaluated to be 1.22 and 4.08 µM, respectively. Moreover, the voltammetric assay demonstrated a good recovery rate, proving the efficacy of the proposed sensor in detecting THB-containing food samples. Conclusions: The outcome of the analysis substantiated the efficacy, selectivity and sensitivity of the developed novel sensor for THB detection.
Copyright (c) 2025 Battira Madappa , Manjunatha J.G. https://creativecommons.org/licenses/by/4.0
A simple UiO-66-NH2@MWCNTs based electrochemical sensor for the sensitive detection of metronidazole
Metronidazole (MRNZ) represents a highly efficacious pharmacological agent for the treatment of protozoal infections, encompassing trichomoniasis, giardiasis, as well as disorders instigated by anaerobic bacteria. In the present investigation, a solvothermal approach is employed to synthesize a composite of multiwalled carbon nanotubes (MWCNTs-COOH) with UiO-66-NH2, resulting in the formation of UiO-66-NH2@MWCNTs. Given the exceptional electrocatalytic characteristics of the UiO-66-NH2@MWCNTs nanocomposite, it was selected as the sensing material and subsequently integrated onto the surface of a bare screen-printed carbon electrode. Under optimal experimental conditions, the developed electrochemical sensor exhibited outstanding metrics of repeatability, stability, selectivity, and reproducibility for detection across an extensive concentration range, specifically from 0.5 μM to 350.0 μM, while achieving a limit of detection of 0.1 μM. Furthermore, the practical application of the sensor was rigorously assessed using MRNZ tablet samples and urine specimens, resulting in a commendable recovery rate of MRNZ ranging from 97.3% to 104.0%. This research elucidates a straightforward, expedited, and significant methodology for the application of UiO-66-NH2@MWCNTs within the domain of electrochemical sensing.
Copyright (c) 2025 Noor Abd Alkhudhur Salman , Israa A. Jassem , Isam Nghaimesh Taeb https://creativecommons.org/licenses/by/4.0
Interaction between albumin originating from persons with uncontrolled diabetes mellitus type 2 and food antioxidants
Background and Purpose: Dietary interventions are a cornerstone in the management of diabetes mellitus type 2. The efficiency, however, depends on pharmacokinetic factors, including interaction of food ingredients with plasma proteins. The concept of this study was to investigate binding effects of three pronounced antioxidants present in the Mediterranean diet: resveratrol, (dihydro)lipoic acid and oleuropein, with albumin isolated from persons with diabetes (HbA1c 63±7 mmol/mol, or 7.9±0.6%) and healthy persons, carrying its intrinsic ligands. Experimental approach: Spectrofuorometric analysis, native electrophoresis and immunoblotting were performed with albumin before and after the interaction with antioxidants. Key results: Fluorescence spectra of the protein from two study groups were similar, whereas a spectrum of methylglyoxal-modified albumin (in vitro oxidised) was different. Calculated binding constants were also similar for two study groups for all three ligands. Kinetic fluorescence measurements revealed significantly altered activity of albumin-bound (dihydro)lipoic acid in persons with diabetes compared to healthy individuals, and no significant difference in the activity of resveratrol in expressing antioxidant protection of albumin upon its exposure to oxidative stress. Conclusions: Although the findings should be further validated using other antioxidants and glycated albumin derived from persons stratified according to the severity of a disease, the results have documented that in vitro methylglyoxal-oxidised albumin, routinely employed for diabetes-simulated investigations, was shown not to reflect this pathophysiological condition properly and not to be adequate for the assessment of relevant nutritional/biochemical potential of food antioxidants.
Copyright (c) 2025 Miloš Šunderić, Dragana Dekanski, Olgica Nedić https://creativecommons.org/licenses/by/4.0
New xanthone and chemical constituents from the aerial parts of Mallotus glomerulatus and their cytotoxicity in MCF-7 and MDA-MB-231 breast cancer cells
Background and purpose: Breast cancer remains a significant global health burden, especially in low-resource settings where standard therapies are limited. This study aimed to explore Mallotus glomerulatus, a lesser-known Thai medicinal plant, as a potential source of novel anti-breast cancer agents. Experimental approach: A phytochemical investigation of M. glomerulatus resulted in the isolation and structural characterization of a novel xanthone (Compound 1) and cleistanthin A (Compound 10) using UV, IR, NMR, and HRMS techniques. Cytotoxicity of the compounds was evaluated in vitro against MCF-7 (ER-positive) and MDA-MB-231 (triple-negative) breast cancer cell lines, along with HepG2 liver cells. Molecular docking studies were conducted to assess their interaction with vacuolar H+-ATPase (V-ATPase). Key results: Compound 1 demonstrated selective cytotoxicity toward MCF-7 cells, whereas cleistanthin A exhibited potent cytotoxicity against both breast cancer lines, with nanomolar IC50 values and a high selectivity index (>100) for MDA-MB-231 compared to HepG2 cells. Docking analysis revealed favourable binding of both compounds at the a–c subunit interface of V-ATPase, suggesting a mechanism involving proton pump inhibition and lysosomal dysfunction. Conclusion: The findings highlight M. glomerulatus, particularly cleistanthin A, as a promising source of safe and affordable anti-breast cancer compounds with potential therapeutic value. Further studies on the mechanism and in vivo efficacy are warranted.
Copyright (c) 2025 Phongthon Kanjanasirirat, Napasorn Chabang, Chanikarn Wongwitayasombat, Patoomratana Tuchinda, Bamroong Munyoo, Niwat Kangwanrangsan, Suradej Hongeng, Bodee Nutho, Sitthivut Charoensutthivarakul https://creativecommons.org/licenses/by/4.0
Prediction of metabolism and solubility of tablet-form drugs according to the biopharmaceutical drug disposition classification system
Background and purpose: Prediction of metabolism and solubility of tablet-form drugs is essential in pharmaceutical development, impacting drug efficacy, safety and formulation strategies. This study aimed to develop predictive models for classifying drugs according to metabolism and solubility within the Biopharmaceutical Drug Disposition Classification System. Experimental approach: A dataset of 220 tablet-form drugs characterized by eleven molecular descriptors was analysed. The Kruskal–Wallis test identified relevant descriptors for metabolism (extensive vs. poor) and solubility (high vs. low) classifications. Probabilistic Neural Networks were employed for predictive modelling, with model parameters optimized to enhance accuracy. Key results: Six molecular descriptors (hydrogen bond acidity, logarithm of the partition coefficient, distribution coefficient, hydrogen bond acceptor count, molecular weight and polar surface area) predicted metabolism class with 97 % accuracy. For solubility classification, five descriptors (dipolarity/polarizability, logarithm of the partition coefficient, distribution coefficient, hydrogen bond donor count and molecular weight) achieved 88 % accuracy. Removal of key descriptors significantly reduced model performance, confirming their importance. Conclusion: The developed models demonstrate robust predictive capability for drug metabolism and solubility classes as defined by the Biopharmaceutical Drug Disposition Classification System, supporting early-stage drug screening based solely on molecular structure. The lower accuracy observed for solubility prediction reflects its complex and multifactorial nature, highlighting the need for further refinement of molecular descriptors. These findings advance the field by providing effective computational tools to predict key biopharmaceutical properties, potentially accelerating the drug development process.
Copyright (c) 2025 Yaroslava Pushkarova, Galina Zaitseva , Kaouthar Bouaalam https://creativecommons.org/licenses/by/4.0
Lipid functionalized silver-coated carbon dot-capped manganese ferrite as drug-free core-shell nanoparticles for multimodal imaging and therapy
Background and purpose: Multifunctional nanoparticles (NPs) are gaining significant interest in biomedical research because of their versatility and potential across various applications, especially in cancer imaging and therapy. These composite systems consist of assorted materials, such as metallic elements, metal oxides, polymers, and carbon-based nanostructures, that are combined to form a single platform featuring improved and synergistic properties. Experimental approach: This study aims to design and synthesize a novel class of silver-coated carbon dot-capped manganese ferrite NPs that were functionalized with lipids (L-Ag@MnFe@C) to improve their cytocompatibility and enable cancer therapy with multimodal imaging functionalities. Carbon-capped manganese ferrite NPs (MnFe@C) were synthesized by a one-pot hydrothermal method, followed by the fabrication of nano-silver coated over the surface (Ag@MnFe@C) using a modified Tollens method, and lipid functionalization was done by the rotary evaporation method for the development of low-cost and biodegradable theranostic agents. Key results: The physicochemical characterization reveals that the engineered L-Ag@MnFe@C exhibits a higher stability, with a zeta potential of -50.6 mV, a hydrodynamic diameter of 279.4 nm and a quantum yield of 69.4 %. The engineered NPs exhibit contrast capabilities in longitudinal magnetic resonance imaging, transverse magnetic resonance imaging, fluorescence imaging, and computed tomography imaging. Furthermore, L-Ag@MnFe@C demonstrated excellent anticancer activity on the lung cancer cell line (A549). Conclusion: Based on these studies, it can be concluded that the engineered L-Ag@MnFe@C exhibits multimodal imaging abilities and demonstrates anticancer properties, thereby confirming it as a potential theranostic agent.
Copyright (c) 2025 Anbazhagan Thirumalai, Pazhani Durgadevi, Venkatakrishnan Kiran, Koyeli Girigoswami, Alex Daniel Prabhu, Agnishwar Girigoswami https://creativecommons.org/licenses/by/4.0
Electrochemical determination of calcium folinate in the presence of methotrexate and 5-fluorouracil using UiO-66/CdS composite modified screen-printed carbon electrode
Background and purpose: Calcium folinate is frequently co-administered with methotrexate and 5-fluo­ro­uracil in chemotherapeutic treatments to enhance therapeutic efficacy and reduce toxicity. Therefore, simple and accurate determination of calcium folinate in the presence of these agents is essential for thera­peutic monitoring and pharmaceutical analysis. Experimental approach: The current work is focused on de­sign­ing and developing a simple and sensitive modified screen-printed carbon electrode (SPCE)-based ele­ctro­chemical sensor for the determination of calcium folinate in the presence of methotrexate and 5-flu­orouracil. For this purpose, a nanostructure of UiO-66/CdS composite was prepared. Then, we used the prepared UiO-66/CdS com­posite to modify SPCE towards the development of an electrochemical sensing platform (UiO-66/ /CdS/SPCE). Key results: The cyclic voltammetry studies revealed that the UiO-66/CdS/SPCE could significantly improve the detection of calcium folinate with a higher response peak current at a lower overpotential compared to other SPCEs. Also, the UiO-66/CdS/SPCE sensor demonstrated a good ability in the quantitative determination of calcium folinate by the differential pulse voltammetry (DPV) method. Based on DPV measurements, a linearity plot was achieved for the concentration range of 0.1 to 300.0 µM calcium folinate with a limit of detection (LOD) of 0.04 µM and a high sensitivity of 0.0503 µA µM-1. Furthermore, the UiO-66/ /CdS/SPCE sensor showed three well-separated oxidation peaks for the simultaneous determination of calcium folinate, methotrexate, and 5-fluorouracil without interfering with each other. Finally, the UiO-66/CdS/SPCE sensor was used to detect calcium folinate, methotrexate, and 5-fluorouracil in real samples, and the values of recovery and relative standard deviation (RSD) were satisfactory. Conclusion: The results from this study show that the designed sensor can be used as an efficient and promising platform for the determination of these species.
Copyright (c) 2025 Raed Muslim Muhibes, Fatma A.Khazaal, Qasim Mezban Salih, Raad Radi Karabat https://creativecommons.org/licenses/by/4.0
Exploring hepatic stellate cell-driven fibrosis: therapeutic advances and future perspectives
Background and purpose: Liver fibrosis, a progressive liver disease arising from viral or metabolic causes, poses a major global health challenge due to its potential progression to cirrhosis and hepatocellular carcinoma. Due to the complex aetiology and epidemiology of liver fibrosis, most therapies fail in the clinic, and very few drugs have been approved by the US FDA. Approach: This review highlights the patho­physiological features of liver fibrosis, with a focus on novel targets in hepatic stellate cells (HSCs), key players in the fibrogenesis process, to develop successful therapeutic approaches using both pharma­cological agents and active targeting strategies. The review also examines current therapeutic strategies targeting liver fibrosis, both in preclinical lab setups and clinical trials. Furthermore, various receptors involved in HSC-mediated liver fibrosis and active drug delivery targeting strategies are reviewed to enhance therapeutic outcomes. This article also integrates existing knowledge to identify research gaps and guide future investigations and clinical translation in liver fibrosis treatment. In addition, novel pathways pertaining to liver fibrosis, such as the RSPO3-LGR4/5-β-catenin cascade, the CD47/YAP/TEAD4 signalling axis, and HAb18G/CD147, are briefly elaborated in the context of therapeutic approaches for arresting HSC activation. Single-cell RNA sequencing of HSCs is presented to provide a clearer picture of liver fibrosis. Conclusion: The review highlights critical research gaps in liver fibrosis therapy and promising active tar­geting strategies and pharmacological interventions to improve therapeutic outcomes. Overall, this review provides a robust foundation for scientists and clinicians to advance active targeting of the disease pathology and to develop new pharmaceutical formulations that are pharmacologically safer and more efficacious.
Copyright (c) 2025 Alka Singh, Ansab Akthar, Prashant Shukla https://creativecommons.org/licenses/by/4.0
Development of a biorelevant dissolution method for inhalation products: Proof of concept using drugs with diverse solubilities
Background and purpose: Due to their unique application and action, inhalation products require specific quality tests, such as Uniformity of Delivered Dose and Aerodynamic Assessment of Fine Particles. While there's no current official requirement for dissolution tests, new draft guidelines are introducing them as a supportive or required measure; however, a universally accepted methodology for such testing remains elusive. The aim of the present study was to explore the discriminatory ability and in vivo predictability of the newly developed dissolution assembly. Experimental approach: The applied experimental approach to biopharmaceutical characterization of inhalation products involved developing a biorelevant method for testing the dissolution rate of the selected active substances. Seven commercially available products, formulated as pressurized metered dose inhalers, containing either salmeterol xinafoate or beclomethasone dipropionate, have been studied. The research strategy combined in vitro testing within silico simulations. Key results: The developed dissolution method did not detect significant differences in the case of products containing highly soluble salmeterol, but it did reveal differences for products containing poorly soluble beclomethasone dipropionate. Moreover, a correlation was identified between the dissolution test results and absorption constants for beclomethasone dipropionate. Conclusion: The obtained results indicated that the investigated products would not be considered bioequivalent based on the aerodynamic particle size distribution. It was demonstrated that a discriminative dissolution method can be developed through a well-established paradigm of dissolution testing, while taking into account the specificities of the inhalation route of administration.
Copyright (c) 2025 Amar Elezović, Sandra Cvijić, Saša Pilipović, Alisa Elezović, Jelena Parojčić https://creativecommons.org/licenses/by/4.0
Comparison of lipophilic and size-exclusion membranes: creating sink conditions with cyclodextrin
Background and purpose: The effective transport of an active pharmaceutical ingredient across various membrane systems is critical for enhancing its bioavailability, especially in formulations involving solubilizing agents. This study aims to investigate the permeability differences of carvedilol between lipophilic (organic solvent) and size-exclusion membranes in the presence of 2-hydroxypropyl-beta-cyclodextrin in just the acceptor compartment or both sides of the membrane using in vitro side-by-side diffusion cell assays. Experimental approach: Cyclodextrins (CDs) on the acceptor side significantly improved flux and permeability for the lipophilic membrane. In contrast, with size-exclusion membranes that allow the permeation of CDs and their complexes, the benefits of sink conditions were completely diminished. When the same amount of CD was introduced on both sides, the negative effect of CD on the donor side surpassed the positive sink effects on the acceptor side, resulting in reduced flux and permeability across all membrane types. Key results: A novel aspect of this work is the assessment of the applicability of a previously described general mathematical equation for sink conditions. Findings indicated that the supersaturation ratio between donor and acceptor compartments serves as the primary driving force of the membrane transport. For the lipophilic membrane, CDs on the acceptor side not only influenced the driving force of the transport by enhancing the solubility of carvedilol in the acceptor compartment but also altered the proportionality coefficient, hence modifying the apparent thickness of the unstirred water layer. The impact was not observed with size-exclusion membranes. The applicability of the mathematical model was additionally evaluated for CD placed on both sides of the membrane. Conclusion: The model effectively describes the impact of CD placed on the donor side when the solid membrane permits only the drug’s permeation, as in the case of a lipophilic membrane, where the solubilizing additive cannot pass through. It is also applicable when the solubilizing additive permeates slowly and has minimal influence on transport, such as with a size-exclusion membrane with a 1 kDa molecular weight cut-off. The model remains suitable if the additive is small enough in hydrodynamic size to permeate the membrane, but no concentration gradient exists to drive its transport, for example, with a 6 kDa size-exclusion membrane containing the same CD concentration on both sides of the membrane.
Copyright (c) 2025 Petra Tőzsér, Szabina Kádár, Edina Szabó, Hajnalka Pataki, Péter Sóti, Péter Laczay, György Tibor Balogh, Bálint Sinkó, Eniko Borbas https://creativecommons.org/licenses/by/4.0
Monolayer graphene/platinum-modified 3D origami microfluidic paper-based biosensor for smartphone-assisted biomarkers detection
Background and purpose: Imbalances in biomarkers such as dopamine and NADH are linked to neurological and metabolic disorders, including Parkinson’s disease, depression, and stroke, underscoring the need for rapid and accessible diagnostics. This study presents a smartphone-assisted, 3D origami microfluidic paper-based analytical device (µPAD) modified with photochemically synthesized graphene/platinum (G/Pt) nanocatalysts for multiplex colorimetric detection of dopamine and NADH. Experimental approach: G/Pt catalysts were prepared using 2.5 to 10 mM Pt precursors under UV irradiation. µPADs were laser-printed on commercial-grade filter paper, patterned, and folded into three layers of 3D Origami. Key results: The optimized 10 mM G/Pt catalyst significantly improved reaction rates (18× faster), leading to a rapid detection time constant of 6.69 and 4.59 s for dopamine and NADH, respectively. Furthermore, the utilization of 10 mM G/Pt catalyst increased colour intensity (2.48×) on the µPAD platform. An application for smartphones integrated with an image processing algorithm was developed using Kotlin to enable automatic quantification of colorimetric signals from saturation and hue channels for dopamine and NADH, respectively. The detection exhibited the lowest mean absolute percentage errors of 0.52 and 0.07 % as well as a limit of detection of 0.56 and 0.99 mM for dopamine and NADH, respectively. Conclusion: The 3D origami structure facilitates efficient fluid handling and multiplex detection, while the nanocatalyst modification improves pore infiltration and sensitivity. This work demonstrates, for the first time, a cost-effective, portable, and high-performance biosensor for dual biomarker detection, offering substantial promise for point-of-care diagnostics in neurological and metabolic health monitoring.
Copyright (c) 2025 Arda Fridua Putra, Annisa Septyana Ningrum, Suyanto Suyanto, Vania Mitha Pratiwi, Muhammad Yusuf Hakim Widianto, Irkham Irkham, Wulan Tri Wahyuni, Isnaini Rahmawati, Fu-Ming Wang, Chi-Hsien Huang, Ruri Agung Wahyuono https://creativecommons.org/licenses/by/4.0
Electrochemical sensors for anticancer drugs used in the targeted therapy of chronic myeloid leukaemia
Background and purpose: Treatment of chronic myeloid leukaemia includes targeted therapy with tyrosine kinase inhibitors (TKIs): imatinib, dasatinib, nilotinib, bosutinib, ponatinib, and asciminib. This review aims to prove that electrochemical sensors provide a reliable alternative to the conventional analytical methods for highly sensitive and cost-effective assay of TKIs in pharmaceutical formulations and biofluids. These platforms have significant advantages in fast detection and portability because they could be designed as miniaturized hand-held devices suitable for real-time point-of-care analysis, providing quick results for enabling personalized therapeutic drug monitoring. Experimental approach: The paper covers recent developments in substrate materials, various electrode designs, the advantages, and limitations of sensors for TKIs, encompassing both basic and applied research. Key results: This is a pioneering study that provides a general review on emerging trends, technologies, and practical applications of electrochemical sensors for TKIs analysis. The article provides researchers with a clear introduction and concise guide to the design and application of electrochemical sensors in the clinical analysis of TKIs. Conclusion: The review is intended to serve as a valuable resource for researchers in navigating the latest developments in TKIs' electrochemical sensing platforms. The fast response, high sensitivities and satisfactory recoveries obtained in blood serum and urine samples show the potential for application of the proposed electroanalytical systems in clinical analysis and optimization of chemotherapeutic treatments.
Copyright (c) 2025 Totka Dodevska https://creativecommons.org/licenses/by/4.0
Topical composite hydrogel incorporating human amniotic membrane and spidroin for the treatment of chronic wounds in diabetes mellitus
Background and purpose: Traditional diabetic chronic skin wound dressings often lack the bioactivity required to promote regeneration in these complex wounds. The use of human amniotic membrane (hAM) has been identified as a promising natural option for diabetic skin wound regeneration, but hAM is susceptible to rejection and release of growth factors, so cells must be decellularized and supplemented with biomaterials such as spidroin, a hydrogel delivery system. This study aims to analyse and evaluate a composite hydrogel combining hAM and spidroin proteins to enhance the healing of diabetic chronic wounds. Experimental approach: Hydrogels were synthesized and characterized using scanning electron microscope (SEM), attenuated total reflectance Fourier transform infrared spectroscopy, physical tests, gel fraction and swelling ratio. Wound healing studies were performed using alloxan-induced diabetic mice. Full-thickness wounds were created and treated with the hydrogel formulations. Macroscopic progress of wound healing was monitored, and histological analysis was performed to assess reepithelialization, inflammatory response, and collagen deposition. Key results: The functional groups of hAMD components were identified at the characteristic absorption peaks of 1650 cm⁻¹, while spidroin showed a peak at 1530 cm⁻¹. In particular, the 10 % composite (hAMD + spidroin) showed significantly faster wound closure compared to the control group and other treatment groups. Histological findings confirmed that the 10 % composite was able to facilitate cell proliferation, reduce inflammation, enhance epithelial regeneration, angiogenesis, fibroblast formation and regular collagen matrix and decrease transforming growth factor beta in the remodelling phase. Conclusion: Composite (hAMD + spidroin) 10 % showed promising wound healing efficacy in diabetic conditions, indicating its potential as a bioactive wound dressing for chronic diabetes.
Copyright (c) 2025 Suyarta Efrida Pakpahan, Anggraini Barlian, Arie Wibowo, Indra Wibowo https://creativecommons.org/licenses/by/4.0
Morphine electrochemical determination using SnO2 nanostructure-modified glassy carbon electrode in the presence of diclofenac
In the present work, SnO2 nanostructures were synthesized and a sensitive voltammetric sensor on a glassy carbon electrode (GCE) was constructed to estimate morphine (MP) in the presence of diclofenac (DLF). Background and purpose: Because diclofenac (DLF) is an NSAID, its administration can reduce postoperative morphine (MP) requirements in adults; for example, standard DLF dosing has been shown to decrease MP use after abdominal surgery. Hence, devising a simple, cost-effective, and swift assay for these compounds in biological and pharmaceutical specimens is indispensable. Experimental approach: SnO2 nanostructures were synthesized, and a sensitive voltammetric sensor on a glassy carbon electrode (GCE) was constructed to estimate MP in the presence of DLF. Cyclic voltammetry was employed to evaluate the electrochemical response of the SnO2 nanostructures/GCE towards MP. Key results: The SnO2 nanostructures exhibited a significant effect on the electrochemical reaction of the electrode toward the MP oxidation. The SnO2 nanostructures/GCE further exhibited a more sensitive detection platform for MP determination with a limit of detection of 0.006 μM using differential pulse voltammetry in a linear range of 0.01 to 340.0 μM. Conclusion: The SnO2 nanostructures/GCE exhibited extremely high electrochemical activities towards the simultaneous oxidation of MP and DLF. Moreover, the SnO2 nanostructures/GCE provided reproducible and stable responses for MP quantitation. The platform prepared showed successful performance for MP and DLF determination in real samples. SnO2 nanostructures exhibited a significant effect on the electrochemical reaction of the electrode toward the MP oxidation. The SnO2 nanostructures/GCE further exhibited a more sensitive detection platform for MP determination with a limit of detection of 0.006 μM using differential pulse voltammetry in a linear range of 0.01 to 340.0 μM. Additionally, the SnO2 nanostructures/GCE exhibited extremely high electrochemical activities towards the simultaneous oxidation of MP and DLF. Moreover, the SnO2 nanostructures/GCE provided reproducible and stable responses for MP quantitation. The platform prepared showed successful performance for MP and DLF determination in real samples.
Copyright (c) 2025 Isam Ngaimesh Taeb, Zainab S. Hadawi, Rasha N. Alibabery https://creativecommons.org/licenses/by/4.0
Bile micelle binding of structurally diverse ionized drug molecules
Background and purpose: Predicting the food effect on oral drug absorption by physiologically based biopharmaceutical modelling (PBBM) remains challenging. The bile micelle unbound fraction (fu) is one of the primary determinants of the negative food effect for high solubility drugs. To calculate the pH-fu profile for PBBM, the bile micelle partition coefficients of ionized and un-ionized drug species (Kbm,z, z: charge) are required. The general rules for the ratio of the partition coefficients of ionized and un-ionized drug species have been reported for the octanol/water (Poct) and phosphatidylcholine liposome/water partition coefficients. However, the general rule for the bile micelle partition coefficient has not yet been investigated. The purpose of the present study was to clarify the general rule for Kbm,z≠0/Kbm,0. Experimental approach: The pH-fu profiles of 4 monovalent weak acids, 8 monovalent weak bases, 2 divalent weak bases, and 2 zwitterion drugs were measured by dynamic dialysis in the pH range about pKa ± 2. Bile micelles consisted of taurocholic acid (TC)/egg lecithin (15 mM/ 3.75 mM). Kbm,z was calculated from the pH-fu profiles. Key results: Kbm,-1/Kbm,0 was ≤ 0.03 for all monovalent acids. Kbm,+1/Kbm,0 ranged from 0.24 to 2.6. Kbm,+2/Kbm,0 was about 0.3. For the two zwitterionic drugs, Kbm,-1/Kbm,±0 was 1.1 and 2.3, and Kbm,+1/Kbm,±0 was 3.9 and 20, respectively. Kbm,0 roughly correlated with Poct (r = 0.68). Conclusion: The bile micelle binding of anionic drug species (z = -1) is generally negligible, whereas that of cationic drug species (z = +1) can be significant. A general rule for Kbm,+1/Kbm,0 was not found. Kbm,+1/Kbm,0 can be greater than 1 in several cases, suggesting an attractive electrostatic interaction between the positive charge of a drug and the negative charge of TC. These points should be considered in food effect prediction.
physiologically-based biopharmaceutics modelling
Copyright (c) 2025 Mayu Konishi, Kiyohiko Sugano https://creativecommons.org/licenses/by/4.0
Nano-modified biosensors for detection of pathogenic diseases: The prospect of smart, multiplex and point-of-care testing
Introduction and Background: The world has witnessed several outbreaks, emergence and re-emergence of infectious diseases throughout the 21st century as a result of climate change, urbanization and migration. Several infectious diseases caused by pathogens such as SARS-CoV-2, Ebola, Zika, Dengue, Marburg viruses, Mycobacterium tuberculosis, etc. have caused a devastating impact on lives and livelihoods around the world. To counter these diseases, medical experts rely on conventional techniques, which include microscopy and serological testing. However, these conventional methods are hindered by several trade-offs, including high cost, longer processing times, low sensitivity, and a likelihood of false positive results. Biomedical sensors have gained momentum in clinical diagnostics due to their low cost, portability, and sensitivity, among other advantages. To improve their performance, scientists have incorporated nanomaterials. Other techniques used to enhance the performance of nanobiosensors include multiplex testing, point-of-care testing (POCT), and smart sensing. Methodology: Thus, in this review, we present a comprehensive overview of the state-of-the-art nanobiosensors for detecting infectious diseases. The review covers key topics which centred around the application of nanotechnology in biosensing, multiplex testing, POCT and smart nano-enhanced biosensors. Findings: The findings of this review highlighted the advantages of biosensors over conventional approaches, with a limit of detection ranging from nanomolar to attomolar concentrations and a time response ranging from 1 to 3 hours. Conclusion: Despite the prospect of nanobiosensors, several limitations such as complexity, very extensive, longer processing time, etc. Moreover, the integration of smart technologies in nanobiosensors can offer several benefits, which include high accuracy, faster detection and prediction.
Copyright (c) 2025 Abdullahi Umar Ibrahim, Pwadubashiyi Coston Pwavodi, Mehmet Ozsoz, Basil Birth Duwa, Irkam Irkham, Yeni Wahyuni Hartati https://creativecommons.org/licenses/by/4.0
Tuneable carbon dots coated iron oxide nanoparticles as superior T1 contrast agent for multimodal imaging
Background and purpose: Multifunctional hybrid nanoparticles garner heightened interest for prospective biomedical applications, including medical imaging and medication administration, owing to their synergistic benefits of constituent components. Therefore, we demonstrated an optimized protocol for synthesizing magnetofluorescent nanohybrids comprising fluorescent carbon dots with magnetic nanoparticles. Experi­mental approach: Carbon dot-coated iron oxide nanoparticles (CDs@Fe2O3) were synthesized with varying citric acid concentrations by a one-pot hydrothermal synthesis method for the development of a low-cost and biocompatible contrast agent (CA) for enhanced multimodal imaging (fluorescent and T1 and T2 weighted magnetic resonance imaging (MRI)) to replace the conventional CAs. Key results: The physico­chemical characterization of the synthesized CDs@Fe2O3 revealed that 3 g of citric acid used for the synthesis of nanoparticles, keeping Fe(II) and Fe(III) ratio 1:2 provides higher stability of -78 mV zeta potential, saturation magnetization of 24 emu/g, with a hydrodynamic diameter of 68 nm. Carbon coating affects surface spins on Fe2O3, resulting in fewer surface-based relaxation centres, making T1 relaxation relatively more prominent. Furthermore, the surface-engineered iron oxide NPs are efficient in producing both T1 and T2 weighted MRI as well as fluorescence-based imaging. The molar relaxivity and molar radiant efficiency derived from phantom studies demonstrate their effectiveness in multimodal medical imaging. The cyto­toxicity assay, haemolysis assay, haematology, and histopathology studies show that the optimized CDs@Fe2O3 are biocompatible, haemocompatible, and negligibly toxic. Conclusion: We can conclude the significant potency of CDs@Fe2O3 for multimodal diagnosis.
super paramagnetic iron oxide nanoparticles
Copyright (c) 2025 Anbazhagan Thirumalai, Palani Sharmiladevi, Koyeli Girigoswami, Alex Daniel Prabhu, Agnishwar Girigoswami https://creativecommons.org/licenses/by/4.0
Fabrication and optimization of freeze-dried isoniazid-loaded poly-ε-caprolactone nanoparticles
Background: Microfluidic nanoprecipitation followed by freeze-drying would yield uniformly sized, stable nanoparticles by preserving their physicochemical property without compromising therapeutic performance. The isoniazid (INH)-loaded poly-ε-caprolactone (PCL) nanoparticles could be developed using a microfluidic technique for the management of tuberculosis. Experimental approach:The INH-loaded nanoparticles were fabricated via a microreactor-assisted nanoprecipitation method and optimization using a design of experiments factorial design approach. The resulting INH-PCL nanoformulation was characterized for particle size, polydispersity index (PDI), zeta potential (surface charge), Fourier-transform infrared spectroscopy, differential scanning calorimetry, X-ray diffraction analysis and field emission scanning electron microscope. Key results:The optimized nanoparticles exhibited an average particle size (248.4 ± 5.372 nm) and high encapsulation efficiency (82.26 ± 4.36 %). Thermal and spectroscopic analyses confirmed the absence of drug-polymer interactions, ensuring formulation integrity; stability studies under accelerated conditions demonstrated negligible changes in particle size, PDI, and zeta potential over the period of 6 months, indicating robust colloidal stability. A scanning electron microscopy study revealed rod-shaped nanoparticles with smooth surfaces. Lyophilization (freeze-drying) enhanced long-term stability, yielding a readily re-dispersible powder (reconstitution index 1.066). Following diffusion-controlled kinetics, in vitro drug release studies in phosphate buffer saline (pH 7.4) showed sustained drug release (92.45 % cumulative release over 48 h). Conclusion: Our results confirm that the INH-loaded PCL nanoformulation combines excellent stability, high drug-loading capacity, and sustained release, key attributes of effective tuberculosis therapy.
Copyright (c) 2025 Eknath Kole, Yuvraj Pawara, Atul Chaudhari, Aniruddha Chatterjee, Jitendra B. Naik https://creativecommons.org/licenses/by/4.0
Leveraging machine learning models in evaluating ADMET properties for drug discovery and development
Background and purpose: The evaluation of ADMET properties remains a critical bottleneck in drug discovery and development, contributing significantly to the high attrition rate of drug candidates. Traditional experimental approaches are often time-consuming, cost-intensive, and limited in scalability. This review aims to investigate how recent advances in machine learning (ML) models are revolutionizing ADMET prediction by enhancing accuracy, reducing experimental burden, and accelerating decision-making during early-stage drug development. Experimental approach: This article systematically examines the current landscape of ML applications in ADMET prediction, including the types of algorithms employed, common molecular descriptors and datasets used, and model development workflows. It also explores public databases, model evaluation metrics, and regulatory considerations relevant to computational toxicology. Emphasis is placed on supervised and deep learning techniques, model validation strategies, and the challenges of data imbalance and model interpretability. Key results: ML-based models have demon­strated significant promise in predicting key ADMET endpoints, outperforming some traditional quantitative structure - activity relationship (QSAR) models. These approaches provide rapid, cost-effective, and repro­ducible alternatives that integrate seamlessly with existing drug discovery pipelines. Case studies discussed in this review illustrate the successful deployment of ML models for solubility, permeability, metabolism, and toxicity predictions. Conclusion: Machine learning has emerged as a transformative tool in ADMET prediction, offering new opportunities for early risk assessment and compound prioritization. While challenges such as data quality, algorithm transparency, and regulatory acceptance persist, continued integration of ML with experimental pharmacology holds the potential to substantially improve drug development efficiency and reduce late-stage failures.
Copyright (c) 2025 Magesh Venkataraman, Gopi Chand Rao, Jeevan Karthik Madavareddi , Srinivas Rao Maddi https://creativecommons.org/licenses/by/4.0
Correlation between A3243G and G9053A mtDNA mutations and ATP levels in diabetes mellitus patients using qPCR and electrochemical aptasensors
Background and purpose: Mitochondrial DNA (mtDNA) mutations can impair oxidative phosphorylation and ATP production, potentially contributing to the pathogenesis of type 2 diabetes mellitus (T2DM). This study aimed to investigate the relationship between mtDNA mutations and ATP levels in blood and urine samples from T2DM patients. Experimental approach: Samples from 60 patients (30 with T2DM + mitochondrial disease [MD] phenotype and 30 with T2DM alone) were analyzed. mtDNA mutations A3243G and G9053A were detected using qPCR with dual-labeled probes (FAM for mutant, HEX for wild type) based on Cq comparisons. ATP concentrations were measured using a screen-printed carbon electrode (SPCE)-based electrochemical aptasensor. Key results: The A3243G mutation was more frequent and had higher heteroplasmy levels than G9053A, particularly in the T2DM + MD group. Although no statistically significant differences in ATP levels were observed between groups, descriptive ranges showed lower ATP concentrations in the T2DM + MD group (314 to 919 µM) compared to the T2DM group (746 to 1130 µM), both below the physiological range (1.500 to 1.900 µM). A similar pattern was found for A3243G mutation levels, while G9053A levels overlapped between groups. Two-way ANOVA showed a significant association between mutation presence and reduced ATP levels. Conclusion: The A3243G mutation may be more directly associated with mitochondrial ATP depletion in T2DM, while the role of G9053A remains inconclusive. This study highlights the potential of combining molecular and electrochemical tools to assess mitochondrial contributions in diabetes.
Copyright (c) 2025 Iman Permana Maksum, Rahmaniar Mulyani, Yeni Wahyuni Hartati, Irkham, Fanny Rizki Rahmadanthi, Serly Zuliska, Toto Subroto https://creativecommons.org/licenses/by/4.0
CRISPR-Cas9-based electrochemical biosensor for the detection of katG gene mutations in isoniazid-resistant tuberculosis
Background and purpose: Multidrug-resistant tuberculosis (MDR-TB) remains a significant challenge in tuberculosis (TB) treatment, driven by simultaneous mutations in the rpoB and katG genes that confer resistance to rifampicin and isoniazid. While many molecular diagnostic tools focus on rpoB, the katG gene is often overlooked despite its critical role in confirming MDR-TB. This study aims to develop a CRISPR/Cas9-based electrochemical biosensor for the rapid and selective detection of katG mutation. Experimental approach: A guide RNA (gRNA) specific to the mutation site on katG gene was designed using the Benchling CRISPR tool, considering on-target and off-target scores, specificity, and cleavage sites within the Mycobacterium tuberculosis genome. The selected gRNA achieved the highest on-target score of 61.2 and an off-target score of 49.0 at cut position 2928, with a PAM sequence of AGG. Its cleavage efficiency was validated experimentally using an electrochemical biosensing platform incorporating a gold-modified screen-printed carbon electrode (SPCE/Au). Redox response enhancement by [Fe(CN6)]3-/4- confirmed the improved performance of the electrode. Key results: The biosensor system detects the target DNA through hybridization with DNA probe-Fc, forming double-stranded DNA (dsDNA) that is recognized and cleaved by the Cas9/gRNA complex. This cleavage significantly reduces the ferrocene oxidation signal, indicating the presence of a katG mutation. Non-mutated target DNA produces a nondetectable ferrocene signal, suggesting that the Cas9 enzyme may remain bound to the electrode without cleavage. The CRISPR/Cas9 electrochemical biosensor demonstrated a low detection limit of 7.5530 aM and a detection range of 101 to 106 aM. Conclusion: The CRISPR/Cas9-based electrochemical biosensor exhibits high sensitivity and specificity for the detection katG mutation, offering a promising platform for rapid MDR-TB diagnostics.
Copyright (c) 2025 Dika Apriliana Wulandari, Muhammad Ihda Hamlu Liwaissunati Zein, Salma Nur Zakiyyah, Safri Ishmayana, Mehmet Ozsoz, Yeni Wahyuni Hartati, Irkham https://creativecommons.org/licenses/by/4.0
Targeting bone in cancer therapy: Advances and challenges of bisphosphonate-based drug delivery systems
Background and Purpose: Bisphosphonates (BPs) are well-known for their strong affinity toward bone mineral matrices and are widely used to inhibit excessive osteoclast activity associated with various bone disorders. Beyond their clinical use, their unique bone-targeting capability has positioned them as promising ligands for drug delivery systems aimed at treating bone-related cancers. Approach: The review analyses published studies on BP-functionalized drug delivery systems, including direct drug conjugates, calcium-based nanomaterials, carbon-based nanostructures, and self-assembling systems such as micelles and liposomes. In vitro assays (e.g. hydroxyapatite binding, cell viability) and in vivo biodistribution studies are discussed to evaluate targeting efficiency and therapeutic outcomes. The impact of BP structure, linker chemistry, and carrier material on drug release and bone accumulation is examined. Key Results: BP-functionalized systems consistently demonstrate improved bone targeting and enhanced drug accumulation at tumour sites compared to non-targeted approaches. Both direct conjugates and nanocarrier-based systems show promising results, with some formulations offering controlled drug release and reduced systemic toxicity. Despite these advances, certain challenges such as burst release and incomplete clinical validation remain. Conclusion: This review highlights the significant progress in BP-based drug delivery platforms for bone cancer therapy, demonstrating their potential to concentrate therapeutic agents at bone tumour sites while minimizing off-target effects. The integration of nanotechnology with BP targeting offers new opportunities for treating bone metastases and primary bone tumours. However, further research is needed to address current limitations and translate these findings into clinical practice.
Copyright (c) 2025 Fariba Ganji, Mohammadmahdi Eshaghi, Hossein Shaki, Lobat Tayebi https://creativecommons.org/licenses/by/4.0