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.
From nanoscale to clinic: The growing impact of nanotechnology in translational drug delivery
Background and purpose: From the early use of liposomes in the 1960s to modern nucleic acid delivery platforms, nanotechnology has shown its value in drug delivery and diagnostic applications. A wide range of nanostructures has been investigated for drug delivery, including inorganic, polymeric and lipid-based nanomaterials. While some of these nanomaterials have reached more advanced stages of clinical development, some even reaching commercialization, new alternatives are continuously being explored. Approach: This review describes the different categories of nanomaterials being used as nanocarriers and provides concrete representative examples of commercially approved products. Key results: Current trends of nanotechnology developments in the pharmaceutical market largely focus on the treatment of cancer, infectious diseases, central nervous system disorders and cardiovascular diseases. At the same time, lipid nanoparticle platforms are gaining relevance in current development pipelines. However, some of the main challenges limiting clinical translation include manufacturability, scale-up, long-term stability, regulatory uncertainty, intellectual property issues and the lack of representative preclinical study models. Conclusion: Nanotechnology has become a fundamental breakthrough in medicine, especially for advanced therapies such as gene silencing or gene editing alternatives. All things considered, no universal nanocarrier fits all biomedical applications; the evolution of the field depends on several platforms demonstrating their individual potential.
Copyright (c) 2026 Ronny Vargas, Fabiola Martos-Kikut, Noelia Martinez-Martinez, Esteban Lara-Guerrero, Catalina Lizano-Barrantes, Jorge Andrés Pacheco-Molina, Miquel Romero-Obon, Khadija Rouaz-El-Hajoui, Encarna García-Montoya, Pilar Pérez-Lozano, Carlos Suñe, Marc Suñe-Pou https://creativecommons.org/licenses/by/4.0
Extracellular vesicles and their translational therapeutic potential
Background and purpose: Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) have emerged as a promising cell-free therapy for osteoarthritis (OA). However, their transition into clinical therapeutics is constrained by unstandardized pharmacokinetics and heterogeneous preclinical reporting. Experimental approach: A meta-analysis of preclinical in vivo OA models evaluating MSC-EV therapy was conducted. Study quality was rigorously assessed using MISEV 2023 (Minimal Information for Studies of Extracellular Vesicles, 2023) criteria and the SYRCLE (Systematic Review Centre for Laboratory animal Experimentation) risk-of-bias tool. Quantitative synthesis was performed for the Osteoarthritis Research Society International (OARSI) histological score, reporting pooled mean differences (MDs) and 95 % confidence intervals (95% CIs), along with heterogeneity (I² statistic) and microRNA (miRNA) cargo analysis. Key results: MSC-EV administration conferred robust structural protection against cartilage degradation. Quantitative synthesis of human-derived MSC-EVs (26 studies) significantly reduced OARSI scores (MD -3.27, 95% CI -4.66 to -1.88; p < 0.0001). Similarly, quantitative synthesis of animal-derived MSC-EVs (8 studies) demonstrated an even more profound effect (MD -5.58, 95% CI -7.13 to -4.03; p < 0.0001). Non-parametric Trim-and-Fill analysis estimated zero missing studies in both datasets, confirming that these effect sizes are highly robust to publication bias. Despite these robust efficacy signals, significant heterogeneity (I² > 84 %) persisted. Meta-regression revealed that arbitrary dosage metrics, whether reported by particle count or protein concentration, failed to reliably predict treatment efficacy, highlighting severe gaps in dose-exposure standardization. Conclusion: MSC-EVs demonstrate highly potent, cross-species efficacy in attenuating OA progression. However, clinical translation is critically bottlenecked by a lack of ADMET (absorption, distribution, metabolism, excretion and toxicity) compliance. Future research must prioritize standardized particle-based dosing, in vivo pharmacokinetic tracking, and rigorous cargo-function validation to enable regulatory approval.
Mesenchymal stem cell-derived extracellular vesicles
Copyright (c) 2026 Riya Mukherjee, Ramendra Pati Pandey, Chung Ming Chang https://creativecommons.org/licenses/by/4.0
Experimentally derived biomimetic chromatographic descriptors for drug-induced phospholipidosis liability prediction
Background and purpose: Drug-induced phospholipidosis (PLD) is a complex intracellular liability commonly associated with the lysosomal accumulation of cationic amphiphilic drugs and remains an important concern in drug development because of its implications for safety, intracellular disposition, and compound prioritization. Although cationic amphiphilicity, membrane interactions, and lysosomal trapping are established features of PLD, experimentally accessible descriptors that capture PLD-relevant membrane affinity remain valuable for early-stage risk assessment. This study aimed to evaluate whether biomimetic chromatographic descriptors can improve the prediction and interpretation of PLD liability by providing experimentally derived information on membrane affinity and protein-binding-related distributional behavior. Experimental approach: A curated dataset of 65 compounds with experimentally reported PLD responses was analyzed using multiple linear regression and ordinal classification approaches. PLD potency was expressed as pEC₅₀, while ordinal models classified compounds into non-inducers, weak/moderate inducers, and strong inducers. Membrane affinity was quantified using immobilized artificial membrane chromatography, expressed as CHI IAM, while protein-related interactions were represented by human serum albumin affinity, log kHSA, and α1-acid glycoprotein affinity, log kAGP. Biomimetic chromatographic descriptors were compared with conventional physicochemical parameters, including log P and log D, to assess their relative predictive and mechanistic value. Key results: CHI IAM-containing models showed strong predictive performance for PLD potency, with external predictivity reaching Q²ext = 0.823. CHI IAM alone also performed strongly, achieving Q²ext = 0.821, indicating that membrane affinity captures a major component of PLD-relevant behavior. In ordinal classification models, CHI IAM alone provided robust discrimination of PLD severity, with a test accuracy of 0.769, macro F1 score of 0.778, and macro-AUC of 0.923. Protein-binding descriptors, particularly log kAGP, showed moderate predictive value but offered limited, model-dependent improvement once membrane affinity was considered. Conventional lipophilicity descriptors did not outperform the biomimetic membrane-affinity descriptor. Conclusion: Biomimetic chromatographic descriptors provide experimentally derived, mechanistically interpretable surrogates for assessing early-stage PLD liability. CHI IAM offers a practical approximation of membrane-affinity behavior relevant to lysosomal phospholipid accumulation and PLD risk. Protein-binding descriptors may provide complementary information related to distributional phenotypes, but their added value appears less consistent than that of membrane affinity. This approach extends beyond conventional lipophilicity-based QSAR by incorporating experimentally measured distribution-relevant properties and may support compound prioritization during drug discovery.
Copyright (c) 2026 Chrysanthos Stergiopoulos, Klara Valko https://creativecommons.org/licenses/by/4.0
Zn-Ni metal-organic framework nanosheets@graphene oxide nanocomposite: A promising voltammetric platform for sensitive determination of doxorubicin
Background and purpose: Doxorubicin (DOX) serves as an anthracycline-based chemotherapy drug to treat multiple types of cancers and sarcomas, which include lung, breast, bladder, leukaemia, liver, head and neck cancers. Experimental approach: The electroanalysis of the trace level of DOX in this study was conducted using a Zn-Ni metal-organic framework nanosheets@graphene oxide nanocomposite (Zn-Ni MOF NSs@GO) after the modification of a screen-printed carbon electrode (Zn-Ni MOF NSs@GO/SPCE). Using chronoampero­metry, cyclic voltammetry and differential pulse voltammetry, the electrochemical characteristics of the sensor as constructed for DOX measurement were examined. Key results: Consequently, the composite sensor demonstrated exceptional electrocatalytic performance in oxidizing DOX within a concentration range of 0.004 to 190.0 μM, with a detection limit of 0.001 μM. It was found that the Zn-Ni MOF NSs@GO/SPCE was effective at determining DOX in real samples, with good recovery values in the 97.1 to 102.0 % range. Conclusion: The designed sensor with cost-effective and good performance could be valuable for therapeutic drug monitoring and clinical diagnostics.
Copyright (c) 2026 Tahereh Kondori, Niloufar Akbarzadeh-T, Somayeh Tajik, Hadi Beitollahi https://creativecommons.org/licenses/by/4.0
Comprehensive review of biosynthesis, plant function, metabolism and new therapeutic bioactivities of flavonoids
Background and purpose: Flavonoids are polyphenolic secondary metabolites synthesized via the phenylpropanoid pathway, serving as a vital biological "immune system" for plants by providing UV-B protection, antimicrobial defence, and pollinator attraction. Experimental approach: This review examines how these plant-based survival tools translate into potent therapeutic agents for human health through a literature review using Google Scholar, Scopus and ScienceDirect, with keywords alone or in combination with other terms. Key results: Current research demonstrates that flavonoids possess diverse bioactivities, including antioxidant, anti-inflammatory neuroprotective properties, with significant efficacy in mitigating cardio­vascular disease, diabetes and cancer. Despite these benefits, the clinical application of flavonoids is currently hindered by limited bioavailability, which prevents consistent therapeutic concentrations in the human body, and a lack of standardized regulatory dosing. Conclusion: This paper identifies three critical pillars for future innovation in the development of structural analogs to (a) improve intestinal absorption, (b) explore drug synergy for enhancing conventional medical treatments and (c) evaluate the microbiome interactions to facilitate personalized nutrition. By integrating plant biochemistry with clinical pharmacology, flavonoids can be transitioned from general dietary components into precise, evidence-based therapies.
Copyright (c) 2026 Iman Permana Maksum, Tati Herlina, Teruna J Siahaan, Yaya Rukayadi, Meiske Naomi Mamuaja https://creativecommons.org/licenses/by/4.0
Electrochemical detection of illicit sibutramine adulteration in herbal weight-loss products using an AgNPs-ErGO modified electrode
Background and purpose: Sibutramine is a synthetic anti-obesity drug that has been banned or restricted in many countries due to serious cardiovascular risks. However, its illegal adulteration in herbal weight-loss products remains a public health concern. This study aimed to develop a simple, sensitive, and reliable electrochemical method for the determination of sibutramine in herbal weight-loss products using a silver-nanoparticle-electrochemically reduced graphene oxide modified glassy carbon electrode. Experimental approach: Graphene oxide, electrochemically reduced graphene oxide, silver nanoparticles and AgNPs-ErGO nanocomposite were synthesized and characterized using X-ray diffraction, Fourier-transform infrared spectroscopy, scanning electron microscopy combined with energy dispersive X-ray spectroscopy, Raman spectroscopy and high-resolution transmission electron microscopy. The AgNPs-ErGO-modified glassy carbon electrode was fabricated and used for sibutramine detection by linear sweep voltammetry. Experimental parameters affecting the analytical signal were optimized. The method was validated according to AOAC guidelines and compared with an HPLC-DAD reference method. Key results: The AgNPs-ErGO/GCE exhibited improved electrochemical response toward sibutramine compared with bare and other modified electrodes. The developed method showed good selectivity, linearity, precision, accuracy, and sensitivity for sibutramine determination. Application to commercial herbal weight-loss samples demonstrated the suitability of the proposed method for real sample analysis, with results comparable to those obtained by HPLC-DAD. Conclusion: The AgNPs-ErGO/ /GCE-based electrochemical method provides a rapid, cost-effective, and reliable approach for detecting sibutramine adulteration in herbal weight-loss products. This work contributes to the development of practical analytical tools for quality control and consumer safety monitoring.
Copyright (c) 2026 Nguyen Dang Thuy Anh, Vo Thi Cam Le, Huynh Van Chung, Ngo Thi Thanh Xuan, Hoang Thi Minh Nguyet, Pham Thi Thanh Ha, Ha Thuy Trang, Le Hoang Hao, Dao Thi Cam Minh, Nguyen Hai Phong, Dinh Quang Khieu https://creativecommons.org/licenses/by/4.0
Mechanisms of action of the hexane extract of Hypericum brasiliense and its component uliginosin B against drug-resistant Staphylococcus aureus
Background and purpose: Microbial resistance is a major global health concern. Methicillin-resistant Staphylococcus aureus is particularly relevant due to its clinical significance, virulence and adaptability. In the search for novel antimicrobial agents, natural products emerged as important sources of bioactive molecules. Previous studies have identified Hypericum brasiliense as a plant with promising antibacterial properties. Experimental approach: We evaluated the susceptibility, mechanisms of action and toxicity of H. brasiliense hexane extract (heHb) and the isolated compounds uliginosin B (uliB), isouliginosin B and japonicin A against reference and drug-resistant S. aureus isolates. Key results: The heHb and uliB demonstrated strong antibacterial activity, exhibiting MICs of 3.125 to 6.25 µg mL-1 and MBCs of 6.25 to 12.5 µg mL-1. Isouliginosin B displayed moderate activity (MIC = 12.5 µg mL-1; MBC ≤50 µg mL-1), whereas japonicin A was inactive. Transmission and scanning electron microscopy revealed pronounced ultrastructural alterations in bacterial cells following exposure to either heHb or uliB, and these exposures induced oxidative stress without compromising plasma membrane integrity. Conversely, the antioxidant N-acetylcysteine partially restored bacterial growth. Docking analysis suggested that uliB might act as a competitive substrate for the NADH-2 enzyme and cytochrome bd oxidase. Moreover, heHb and uliB inhibited biofilm formation and disrupted mature biofilms. Cytotoxicity assays (Vero and HaCaT lineages) showed CC₅₀ >90 µg mL-1, and haemolysis occurred only at the highest concentrations. In vivo assessment using Galleria mellonella confirmed low toxicity. ADMET predictions indicated a favourable pharmacokinetic profile for uliB. Conclusion: UliB is likely a key bioactive compound of H. brasiliense, with promising therapeutic potential against S. aureus.
Copyright (c) 2026 Julia Chaves Scaffo, Sofia Trindade Mussi da Silva, Vitor Won-Held Rabelo, Leandro Stefano Sangenito, Lucas da Silva Abreu, Thaís P. Mello, Leandro Rocha, André Luis Souza dos Santos https://creativecommons.org/licenses/by/4.0
Cholinesterases inhibition profiles with Ugi-derived peptide­mimetics: A combined experimental and computational study
Background and purpose: Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) are crucial enzymes implicated in various neurological disorders, including Alzheimer’s disease. Developing selective inhibitors for either enzyme is one of the key therapeutic strategies. This study aimed to synthesize and evaluate a novel series of peptidomimetics for their ability to inhibit both human AChE and BChE, with a focus on identifying compounds exhibiting joint inhibitory activity or selectivity for BChE. Experimental approach: Eleven peptidomimetics were synthesized using the Ugi four-component reaction. In vitro enzyme inhibition assays were performed to determine the dissociation constants (Ki) for both human AChE (hAChE) and human BChE (hBChE). Principal component analysis was employed to analyse the inhibition data and map compound selectivity. To investigate the molecular interactions between the peptidomimetics and the BChE active site, quantum-chemical docking simulations were conducted. Key results: All synthesized compounds exhibited reversible, micromolar inhibition of both hAChE and hBChE. Two compounds demonstrated significant BChE selectivity, with 279- and 169-fold higher preference for BChE, respectively. Principal component analysis revealed distinct clusters correlating with preferential binding to either enzyme. Docking simulations supported these findings, highlighting key stabilizing interactions (primarily π-π stacking) between the peptidomimetics and BChE, explaining superior selective and joint inhibitory activity. Conclusion: This work demonstrates the successful synthesis and characterization of novel peptidomimetics with varying degrees of hAChE and hBChE inhibition, including compounds with notable BChE selectivity. The combination of experimental data and computational modelling provides valuable insights into the structural basis of enzyme inhibition and establishes a foundation for rational design of more potent and selective cholinesterase inhibitors based on the designed scaffold.
Copyright (c) 2026 Alma Ramić, Toni Divjak, Lucija Hadrović, Matej Pavlinić, Ana Matošević, Anita Bosak, Jakov Borovec, Bruna Bakota, Tomica Hrenar, Ines Primožič https://creativecommons.org/licenses/by/4.0
Engineering affibody-based biosensing platforms for cancer biomarker detection
Background and purpose: Cancer is one of the most life-threatening diseases and has the highest mortality rate worldwide. Delayed cancer diagnosis remains a major challenge in cancer treatment. Currently, conventional diagnostic methods still have several limitations, resulting in many cancer cases being detected only at advanced stages. Experimental approach: This review was conducted as a literature study of research on the development of affibody-based biosensors for cancer biomarker detection. The review discusses the characteristics of affibodies as bioreceptors, affibody synthesis methods, and their applications in electro­chemical and optical biosensors. Key results: Various studies have shown that affibody-based biosensors exhibit high sensitivity and specificity for detecting cancer biomarkers such as human epidermal growth factor receptor 2, tumour necrosis factor-alpha, epidermal growth factor receptor, carcinoembryonic antigen and alpha-fetoprotein. The integration of affibodies into biosensor platforms enables low detection limits, wide linear ranges and good analytical performance in biological samples. Conclusion: Affibody-based biosensors show great potential as platforms for cancer diagnosis. The use of affibodies as bioreceptors offers several advan­tages over antibodies and aptamers, particularly ease of synthesis, high stability and strong binding affinity.
Copyright (c) 2026 Zhafira Fauziah, Robeth Viktoria Manurung, Yuspian Nur, Dika Apriliana Wulandari, Salma Nur Zakiyyah, Irkham Irkham, Yeni Wahyuni Hartati https://creativecommons.org/licenses/by/4.0
Design, synthesis and antitubercular evaluation of novel 5,6-diphenyl-1,2,4-triazine-piperazine derivatives targeting mycobacterial dihydrofolate reductase
Background and purpose: Tuberculosis (TB), a serious global health concern, continues to contribute to the global health burden, underscoring the urgent need to discover potent antitubercular agents. In the present study, a series of novel 5,6-diphenyl-1,2,4-triazine-piperazine derivatives were synthesized, and their potential for anti-tubercular activity was assessed. Experimental approach: The antitubercular potential of the synthesized compounds was assessed using the microplate alamar blue assay (MABA). Cytotoxicity studies were carried out on RAW 264.7 macrophages. To assess the mode of action of the synthesized compounds, docking analysis of the active compounds was performed on two key enzymes of Mycobacterium, decaprenylphosphoryl-β-D-ribose 2′-epimerase and Mycobacterium tuberculosis-dihydro­folate reductase (Mtb-DHFR). Furthermore, molecular dynamics simulations and density functional theory calculations were performed to validate the stability of the ligand–protein complexes and the electronic properties of the lead compounds. Key results: The results revealed promising anti-tubercular activity for the synthesized compounds. Among these, compounds 2-((5,6-Diphenyl-1,2,4-triazin-3-yl)thio)--1-(4-(4-fluoro­benzoyl)pi­perazin-1-yl)ethan-1-one (FP3) and 2-((5,6-diphenyl-1,2,4-triazin-3-yl)thio)-1-(4-(4-methylbe­nzoyl) piperazin-1-yl)ethan-1-one (FP8) exhibited potent activity with an minimum inhibitory concentration of 1.6 µg mL⁻¹, along with promising cytotoxicity profiles against RAW 264.7 macrophage cells. Docking studies revealed potent docking scores compared to the standard, thereby confirming the involvement of the DHFR enzyme. Interaction analysis revealed stable hydrogen-bond interactions, π-π stacking, and hydrophobic interactions with the active-site residues of the DHFR enzyme. Additionally, molecular dynamics simulation validated the stability of the interactions and the structural integrity of the complexes, while density functional theory calculations supported the desirable electronic properties of the lead compounds. Conclusion: The combined results of the experiments and calculations validated the potential of FP3 and FP8 as DHFR-targeted antitubercular agents. The study highlights the potential of 5,6-diphenyl-1,2,4-triazine-piperazine derivatives as promising candidates for further anti-tubercular drug development.
Copyright (c) 2026 Uday Thakkar, Moksh Shah, Pratik Khona, Harnisha Patel, Mange Ram Yadav, Salman Patel, Chanchal Singh, Renuka Bhamre, Afzal Nagani https://creativecommons.org/licenses/by/4.0
Synthesis and characterization of bimetallic nanocomplex: Application for electrochemical determination of idarubicin as anti-cancer drug
Background and purpose: Cancer chemotherapy with antineoplastic drugs destroys cancer cells through complete cell death or stops cell development while protecting healthy cells from damage. Monitoring anticancer therapeutics in blood and tissues is important for determining their fate. Experimental approach: A novel binuclear complex with the formula [Cu(opd)2(H2O)(μ-SCN)Ni(opd)(SCN)3] (opd = o-phe­nylenediamine) was synthesized and characterized using Fourier transform infrared spectroscopy and UV-Vis spectroscopy. The solvothermal method was used to create a nanoscale version of the binuclear complex. X-ray powder diffraction, scanning electron microscopy, UV-Vis and FT-IR spectroscopy were used to characterize the nanocomplex. The solvothermal approach produced a nanocomplex with an average size of around 56 nm. The complex was tested for its antimicrobial properties on Gram-positive Staphylococcus aureus and Enterococcus faecalis, as well as Gram-negative Escherichia coli and Pseudomonas aeruginosa. Additionally, a screen-printed graphite electrode modified by a synthetic nanocomplex (Cu-Ni/SPGE) was presented as an improved electrochemical sensor for the detection of idarubicin (IRN). Key results: This sensor has a linear dynamic range from 0.01 to 3.0 μM and an impressive limit of detection of 0.003 μM under ideal testing circumstances. Conclusion: The researchers used a Cu-Ni/SPGE system to perform electrochemical measurements on IRN. The Cu-Ni/SPGE outperformed the untreated SPGE in terms of IRN oxidation. The antibacterial activity of the complex was also studied.
Copyright (c) 2026 Thekrayat J Joodi Jassim, Raheem Kubaish Barid, Haider Dakhal Hamza https://creativecommons.org/licenses/by/4.0
Assessing oxime reactivation efficacy using principal component analysis: Insights from nerve agents inhibited human butyrylcholinesterase
Background and purpose: The toxicity of organophosphorus compounds (OPs) and related nerve agents (NAs) impairs the cholinergic system via irreversible inhibition of acetylcholinesterase (AChE) activity by phosphylation of the catalytic serine. Reactivation of the enzyme activity largely depends on the structural compatibility between the enzyme, an oxime reactivator, and the specific OP compound. Experi­mental approach: For this study, we used our recently published data on the reactivation of human butyryl­choli­nesterase inhibited by the NAs sarin, cyclosarin, tabun and VX, using a library of 115 oximes. We compared these results with oximes’ ADME (absorption, distribution, metabolism, and excretion) parameters relevant to central nervous system activity using principal component analysis (PCA). PCA facilitated the examination of these relatively large datasets by increasing interpretability while minimizing information loss. Key results: Three components with eigenvalues above 1 resulted in 72 % of the cumulative proportion of variance and described 27 variables. PC1 created transformed data that had negative values for most oximes with high reactivation potential, while showing large positive values for oximes with moderate and low efficacy. Distribution of 27 loadings, representing 27 variables, produced a set of 9 positive and 18 negative loadings representing negative and positive data correlation. The efficacy of oxime reactivation was highly correlated with the parameters describing its structure: molecular weight, rotational bonds, molecular volume, and molecular surface area. Conclusion: A large dataset was efficiently analysed by maximizing the preservation of variability and generating new, uncorrelated variables. To our knowledge, this study is the first to apply PCA to assess oxime’s reactivation efficacy, thus providing insights into the relationships between oxime properties and their efficacy in restoring OP-inhibited cholinesterase activity.
Copyright (c) 2026 Goran Šinko, Tena Čadež, Zrinka Kovarik, Nikolina Maček Hrvat https://creativecommons.org/licenses/by/4.0
Magnetoreceptive CRY/MagR complexes: linking circadian redox signalling to protein aggregation in Alzheimer’s and Parkinson’s disease
Background and purpose: Neurodegenerative disorders such as Alzheimer’s disease (AD) and Parkinson’s disease (PD) pose an escalating challenge to neuroscience, as disease-modifying therapies remain elusive despite substantial advances in molecular and cellular understanding. These disorders share convergent pathological features, including protein misfolding and aggregation, mitochondrial dysfunction, oxidative stress, impaired proteostasis, and disruption of circadian regulation. Identifying integrative frameworks that connect these processes is therefore essential for advancing conceptual models of neurodegeneration. This review examines magneto-proteins, with a particular focus on CRY/MagR-based magnetoreceptor complexes, as emerging biological systems that may intersect with key molecular pathways implicated in AD and PD. Experimental approach: We synthesized literature from neuroscience, biophysics, and circadian biology to evaluate the potential relevance of magnetoreceptor mechanisms to AD and PD pathology. We first summarized the core neuropathological mechanisms underlying both diseases, including amyloid-β and tau pathology in AD and α-synuclein aggregation and dopaminergic vulnerability in PD. We then outlined the biophysical foundations of magneto-protein function, emphasizing cryptochrome-mediated radical pair mechanisms, iron-sulfur cluster-dependent magnetic sensitivity, and their established roles in redox signaling and circadian biology. Key results: Accumulating experimental evidence from cellular and animal models suggests that CRY/MagR-associated pathways can modulate oxidative stress, mitochondrial bioenergetics, protein aggregation dynamics, autophagic processes, and circadian control of neuronal metabolism. These processes closely overlap with molecular determinants of neuronal vulnerability in AD and PD. However, direct validation in mammalian and human systems remains limited and controversial, representing a critical knowledge gap. Conclusion: The mechanistic convergence between magnetoreceptor biology and neurodegenerative pathology warrants critical evaluation but remains largely speculative in humans. By integrating findings across disciplines, this review positions CRY/MagR-based magneto-proteins as a conceptual platform for exploring how magnetic field-responsive molecular systems may inform our understanding of neurodegenerative disease mechanisms, while emphasizing the need for rigorous mammalian validation.
Copyright (c) 2026 Mozhgan Alipour, Behnam Hajipour-Verdom, Faria Ashrafi, Sara Rahmati Roodsari, Shabnam Nohesara, Alireza Zali, Farzad Ashrafi https://creativecommons.org/licenses/by/4.0
Enhanced anti-inflammatory and antibacterial efficacy of a novel gum ghatti-infused polymeric film for ocular drug delivery
Background and purpose: Ocular inflammation is a key challenge after ocular surgery, and resistance has developed in the bacterial strain. Primarily, the short residence time of the ocular formulation makes it more effective in treating and alleviating inflammation. Experimental approach: In this study, a moxifloxacin-incorporated gum ghatti-infused poly(vinyl alcohol-chitosan) polymeric film was developed using the solvent casting method. Various properties of the ocular composite film, including mucoadhesiveness, strength profile, and crystal size, were evaluated. Key results: The prepared composite film exhibited a red-yellow hue. XRD and DSC analyses revealed that the drug in the formulation is amorphous. The release profile reduces the release rate and follows both Fickian and non-Fickian mediated pathways. A clear zone of inhibition was observed against both Gram-negative (Pseudomonas aeruginosa) and Gram-positive (Staphylococcus aureus) bacteria. The in vivo anti-inflammatory potential of carrageenan was observed against the prepared formulations, and within 1.5 hours, redness and inflammation diminished. Corneal integrity was maintained, with no dark spots observed in the corneal region, confirming that no coagulant or thrombosis of blood occurred in the eye. Conclusion: Based on the foregoing discussion, the formulation shows potential for treating ocular conjunctivitis and can be safely used for pink eye, bacterial conjunctivitis, or allergic conjunctivitis.
Copyright (c) 2026 Swagatika Das, Sk Habibullah, Yashwant Giri, Amulyaratna Behera, Gurudutta Pattnaik, Biswaranjan Mohanty https://creativecommons.org/licenses/by/4.0
Prediction of bile salt export pump inhibition using biomimetic chromatographic descriptors: Integrating membrane affinity and protein binding
Background and purpose: Bile salt export pump (BSEP) inhibition is a key mechanistic driver of cholestatic drug-induced liver injury, yet current prediction approaches rely mainly on in vitro potency and calculated physicochemical descriptors that do not adequately reflect local exposure at the canalicular membrane. This study aimed to evaluate whether biomimetic chromatographic descriptors could improve predictions of BSEP inhibition by incorporating mechanistically relevant information on membrane affinity and protein binding. Experimental approach: A dataset of 62 structurally diverse compounds with reported BSEP inhibition data was compiled and modelled using multiple linear regression. Biomimetic descriptors derived from immobilized artificial membrane chromatography and human serum albumin affinity (log kHSA) were compared against conventional descriptors such as lipophilicity and molecular weight. Model performance was assessed using internal and external validation, graphical diagnostics, Y-randomization, and applicability domain analysis. Key results: Models based on biomimetic descriptors demonstrated superior, more balanced predictive performance than conventional physicochemical models, with greater robustness and external predictivity. The combination of membrane-affinity and protein-binding descriptors provided a more accurate representation of the determinants governing BSEP interactions. Conclusion: Biomimetic chromatographic descriptors provide an experimentally grounded approximation of membrane-proximal exposure, a key determinant of BSEP interactions that conventional descriptors do not capture. This approach extends beyond traditional quantitative structure-activity relationship by incorporating distribution-relevant properties into predictive modelling and offers a simple, interpretable framework to support early identification of transporter-mediated toxicity risk in drug discovery.
Structure-activity relationship of captopril derivatives as New Delhi metallo beta-lactamase 1 inhibitors
Background and purpose New Delhi Metallo beta-lactamase-1 (NDM-1) is a zinc-dependent enzyme that confers resistance to several antibiotics; therefore, there is an urgent requirement for effective inhibitors. Captopril has been exploited as a scaffold in the design of NDM-1 inhibitors; however, a comparative evaluation of these derivatives from structure activity relationship perspective has not been conducted. This review aimed to evaluate captopril-derived NDM-1 inhibitors and to identify possible structure-activity relationships that govern their NDM-1 inhibitory action. Experimental approach: The literature was searched in a structured manner using scholarly databases to locate original studies that reported captopril derivatives and evaluated them in vitro against NDM-1 with the explicit reporting of the inhibitory concen­tration values (IC50). Eligible studies were filtered using predefined criteria and analysed using a qualitative approach, because heterogeneity in assay conditions and experimental methods prevented a direct quantitative comparison across studies. Important findings: The activity of captopril derivatives depends on the free thiol group (masking it reduces activity), with stereochemistry governing optimal binding orientation within the NDM-1 active site, hydrophobic substitutions enhance activity only within steric limits, and the carboxylate motif serves as a secondary anchoring feature. Conclusion: Captopril emerges as a promising scaffold for NDM-1 inhibitors and reveals significant structural features associated with NDM-1 inhibitors. Despite limited in vivo data and heterogeneity in assay conditions, the findings provide a rational framework for optimizing captopril-inspired NDM-1 inhibitors.
Copyright (c) 2026 Ikhlas Jarrar https://creativecommons.org/licenses/by/4.0
Synthesis of NiO nanostructures as electrode materials for the voltammetric determination of epinephrine in the presence of acetaminophen
Background and purpose: Epinephrine, also called noradrenaline, is an important chemical mediator in the central nervous system of mammals. Experimental approach: The hydrothermally synthesized NiO nano­structures were used for the modification of a screen-printed electrode, and they were characterized and used in this work for the voltammetric determination of epinephrine in the presence of acetaminophen. Several electrochemical techniques were employed to investigate the electrochemical properties of NiO-modified screen-printed carbon electrode, including cyclic voltammetry, differential pulse voltammetry and chronoamperometry. Key results: The differential pulse voltammetry peak current of epinephrine was linear with concentration in the range from 0.01 to 400.0 μmol L-1, and the limit of detection was 0.005 μM with a sensitivity of 0.1167 μA L μmol-1. The findings indicated that the current signals for epinephrine were significantly amplified, a result attributed to the superior catalytic performance of the NiO nanostructures. Furthermore, the oxidation peaks for epinephrine and acetaminophen were distinctly separated, with potential differences of approximately 360 mV and 545 mV, respectively. Conclusion: Furthermore, the NiO modified screen-printed carbon electrode was successfully applied to quantify epinephrine and acetamino­phen in both urine samples and pharmaceutical formulations. The results indicated satisfactory recovery rates for the target analytes. Consequently, this electrode is suitable for the analysis of both compounds in pharmaceutical and clinical laboratory settings.
Copyright (c) 2026 Mais A. Mohammed, Shemaa A. Soud, Reem Adham Al-Bayati, Shimaa B. Al-Baghdadi https://creativecommons.org/licenses/by/4.0
Leveraging network pharmacology in the treatment of asthma
Background and purpose: Asthma, a chronic airway inflammatory disorder driven by multifaceted genetic, cellular and molecular interactions, remains inadequately managed by single-target therapies due to incomplete disease control and adverse effects; this review aimed to explore network pharmacology's role in elucidating multi-target mechanisms of phytotherapeutic agents for asthma, with a focus on integrating ADMET/DMPK profiling to predict clinical translatability and safety. Experimental approach: We employed network pharmacology methodologies including target prediction (e.g. via PharmMapper, PubChem), protein-protein interaction network construction (STRING, Cytoscape), pathway enrichment analysis (KEGG, Reactome), molecular docking (AutoDock) and ADMET/DMPK modelling (SwissADME, pkCSM) to dissect multi-component herbal formulations, complemented by literature-mined experimental validations. Key results: Analyses identified key asthma-related targets (e.g. IL-17, TNF) and pathways (JAK-STAT, PI3K-AKT), revealing quercetin and kaempferol's multi-target efficacy in reducing airway inflammation and immune dysregulation; favourable ADMET profiles (high oral bioavailability, low toxicity) and DMPK parameters (metabolic stability via CYP inhibition) supported their therapeutic potential in herbal combinations. Conclusion: Network pharmacology, enhanced by ADMET/DMPK integration, advances a holistic under­standing of herbal asthma treatments, promoting safe, multi-target drug development. Limitations include data gaps in multi-omics validation and herbal standardization, with future directions leveraging AI-driven predictions for personalized pharmacotherapy.
Copyright (c) 2026 Sarthi Ahuja , Richard Cherehani Kashindye , Divya Yadav, Priyanka Chaudhary, Rakesh Yadav https://creativecommons.org/licenses/by/4.0
A high-performance voltammetric sensor based on Co/Ni-metal-organic framework modified electrode for the determination of dopamine in the presence of tyrosine
Background and purpose: The central nervous, renal, hormonal, and cardiovascular systems depend on dopamine. Therefore, a straightforward, sensitive, and selective method for detecting DA is needed to track DA levels in the human body. Experimental approach: Co/Ni-metal-organic framework was developed via a one-pot hydrothermal synthesis. The electrochemical sensor developed for dopamine measurement used Co/Ni-metal-organic framework materials on screen-printed carbon electrodes. The Co/Ni-metal-organic framework on a screen-printed carbon electrode exhibits excellent electrocatalytic activity for dopamine oxidation, owing to its high electron-transfer rate. Key results: The electrocatalytic activity of Co/Ni-metal-organic framework on a screen-printed carbon electrode significantly improves dopamine oxidation, yielding higher peak currents and lower oxidation potentials than the bare screen-printed carbon electrode. The sensor detected dopamine with a linear response, ranging from 0.01 to 660.0 µmol L-1, with a limit of detection of 0.007 µmol L-1. To measure tyrosine and dopamine simultaneously, differential pulse voltammetry was used. The separation between tyrosine and dopamine reached 150 mV. Conclusion: Successful target-analyte identification using the proposed voltammetric sensor was achieved, detecting both dopamine and tyrosine in actual sample tests.
Copyright (c) 2026 Dhurgham Hani Kadhim Alalwan, Saja Haider Fadhil, Muntaha Mahmood Abed, Noor Kareem Aead, Hussein Ali Qabel https://creativecommons.org/licenses/by/4.0
Neuroprotective cellular and molecular mechanisms of physical exercise on neurodegenerative diseases
Background: Neurodegenerative diseases such as Alzheimer's, Parkinson's, and Huntington's disease are characterized by a progressive loss of neuronal function and loss of synaptic capacity. Physical exercise (PE) is one of the non-clinical techniques for the management of brain health and neurodegeneration. Mechanisms: PE enhances the body's metabolic functions through cellular and molecular changes. It trades off metabolic functions, energy expenditure, and signalling processes to ensure physiological homeostasis and defence against disease. Exercise produces cascades, at the molecular level, including neurotrophic signalling, similar to those generated by drugs. It increases the levels of the brain-derived neurotrophic factor (BDNF), insulin-like growth factor 1 (IGF-1), and vascular endothelial growth factor (VEGF). These elements favour the growth of new neurons, vascular enlargement, and synaptic plasticity. PE also induces microglial cells to attain a neuroprotective, anti-inflammatory phenotype, reduces detrimental cytokines, promotes cellular clearance through autophagy, restores neurotransmitter homogenisation, and induces hippocampal cell formation. Collectively, it acts as a powerful modulator of health and brain activity. Implications: The aggregate processes enhance neuronal vulnerability to harm, aid cognitive functioning, and ensure the stability of neural networks. Conclusion: PE is an exciting additive therapy for preventing and treating various neurodegenerative disorders by orchestrating a diverse array of cellular and molecular responses.
Copyright (c) 2026 Saswati Swagatika Sahoo, Pratap Kumar Sahu, Nishigandha Sa, Anindita Behera https://creativecommons.org/licenses/by/4.0
Linking biomimetic binding measurements to pharmacokinetic models of volume of distribution and hepatic clearance
Background and purpose: The steady-state volume of distribution reflects the extent to which drugs partition between plasma and tissues and is closely related to the tissue-to-plasma partition coefficient. In pharmacokinetics, different modelling frameworks have led to ongoing debate regarding the role of plasma protein binding and the importance of unbound drug exposure in determining both distribution and clearance. This review aims to clarify the relationship between distribution and elimination models and to assess how experimental binding measurements can support their mechanistic interpretation. Experimental approach: Established pharmacokinetic relationships linking volume of distribution (Vd), clearance and half-life were analysed alongside biomimetic chromatographic measurements of drug binding to human serum albumin and phospholipid membranes using immobilized artificial membrane (IAM) chromatography. Literature data for marketed drugs were evaluated to examine how these experimental descriptors relate to distribution and clearance behaviour. Key results: The analysis shows that distribution and clearance models describe complementary aspects of drug disposition rather than contradictory processes. Tissue binding, as reflected by phospholipid affinity measured by IAM chromatography, plays a dominant role in determining Vd, while plasma protein binding influences both distribution and clearance through its effect on the fraction of drug unbound in plasma. The apparent paradox of plasma protein binding arises because changes in unbound fraction affect both processes simultaneously. Conclusion: This work demonstrates that biomimetic binding measurements provide a mechanistically meaningful bridge between physicochemical properties and pharmacokinetic behaviour. By integrating experimental binding data with pharmacokinetic models, the study advances understanding of how distribution and clearance are linked, supporting more informed decision-making in early drug discovery while highlighting that clearance remains influenced by additional factors beyond non-specific binding.
Copyright (c) 2026 Klara Livia Valko https://creativecommons.org/licenses/by/4.0
Mortality prediction with adjuvant tamoxifen in breast cancer: Machine learning-integrated explainable artificial intelligence and Bayesian model results
Background and purpose: Tamoxifen is a cornerstone of adjuvant endocrine therapy for breast cancer, yet significant inter-individual variability in treatment response and mortality exists. Identifying robust predictors of outcomes remains a critical need. This study integrated machine learning, explainable artificial intelligence (XAI) and Bayesian modelling to predict mortality and identify key prognostic factors in breast cancer patients receiving adjuvant tamoxifen. Experimental approach: We analysed data from 568 patients from the International Tamoxifen Pharmacogenomics Consortium database. The outcome was all-cause mortality, with predictors including age, race, menopausal status, tumour size, estrogen receptor status, radiation treatment, and CYP2D6 metabolizer status. Four algorithms, logistic regression, random forest, eXtreme Gradient Boosting (XGBoost) and support vector machine, were developed and validated. Model performance was assessed using accuracy and area under the receiver operating characteristic curve (AUC). SHapley Additive exPlanations (SHAP) analysis provided interpretability for the XGBoost model, and Bayesian logistic regression with weakly informative priors was employed for probabilistic inference. Key results: The overall mortality rate was 19.4 %. XGBoost demonstrated the highest discriminative ability (AUC 0.833; 95 % confidence interval: 0.725 to 0.941), while random forest exhibited superior sensitivity for identifying deceased patients (83.3 %). SHAP analysis revealed that white race, increased age, absence of radiation treatment, larger tumour size and the CYP2D6 poor metabolizer (PM/PM) genotype were associated with elevated mortality risk, whereas the extensive metabolizer (EM/EM) genotype was protective. Significant variability was observed in exploratory subgroup analyses, with the model achieving excellent discrimination in patients without radiation treatment (AUC 0.901) and those with the EM/PM genotype (AUC 0.956) but failing to identify any mortality events in the Caucasian subgroup. Bayesian logistic regression yielded comparable performance to frequentist methods (AUC 0.820), with tumour size emerging as a consistently strong predictor in partial dependence plots. Conclusion: Integrating machine learning with XAI and Bayesian approaches effectively identified key predictors of mortality in tamoxifen-treated breast cancer patients. However, marked heterogeneity in model performance across subgroups highlights the critical need for external validation and careful evaluation of algorithmic fairness before clinical implementation.
Copyright (c) 2026 Kannan Sridharan, Gowri Sivaramakrishnan https://creativecommons.org/licenses/by/4.0
Potential of extracellular vesicles from human Wharton’s jelly and golden berries (Physalis peruviana) combined with polyvinyl alcohol/chitosan/fibroin hydrogel for wound healing: In vitro approaches on 1BR3 cell line
Background and purpose: The development of biocompatible delivery systems capable of enhancing wound healing remains a major challenge in drug delivery and regenerative medicine. Hydrogels represent promising wound dressings due to their ability to maintain a moist microenvironment, absorb exudates, and enable controlled release of bioactive agents. Recently, plant-derived exosome-like nanoparticles (PDENs) have emerged as a novel, non-toxic, and cross-kingdom therapeutic modality. Experimental approach: In this study, we investigated PVA/chitosan/fibroin-based hydrogels as a delivery platform for PDENs isolated from Physalis peruviana (PENC), with human Wharton’s Jelly mesenchymal stem cell-derived exosomes (hWJ-MSC-Exo) used as a biological comparator. Key results: PENC and hWJ-MSC-Exo were isolated and characterized in terms of size, morphology, and protein content. Composite hydrogels containing chitosan, polyvinyl alcohol (PVA), and fibroin (4% and 10%) were fabricated via freeze–thawing and characterized for hydrophilicity, swelling behavior, water content, biodegradability, and protein release profiles. The biological performance of hydrogel-released media incorporating PDENs or hWJ-MSC-Exo was evaluated in vitro using human dermal fibroblast 1BR3 cells through cytotoxicity, proliferation, and scratch migration assays. The fabricated hydrogels exhibited hydrophilic surfaces (contact angle <90°), high swelling capacity (>100%), low water content, and gradual biodegradation over 10 days. Protein release peaked on day 3, indicating favorable release kinetics for bioactive delivery. All hydrogel formulations demonstrated good biocompatibility, with cell viability exceeding 75%. Notably, hydrogels loaded with PENC significantly promoted fibroblast proliferation and migration, with performance comparable to or exceeding that of hWJ-MSC-Exo-loaded hydrogels, particularly in fibroin-containing formulations. Conclusion: These findings highlight the potential of Physalis peruviana-derived PDENs as a novel bioactive agent for wound healing and demonstrate that PVA/chitosan/fibroin hydrogels serve as an effective delivery platform to enhance their biological activity. This study supports the translational potential of PDEN-based hydrogel systems for future wound healing applications.
Plant-derived exosome-like nanoparticles
Copyright (c) 2026 Afrida Rizky Nurfajrin, Indra Wibowo, Anggraini Barlian https://creativecommons.org/licenses/by/4.0
Simultaneous quantification of drug and coformer during cocrystal dissolution using in situ UV spectroscopy and multicomponent analysis
Background and purpose: The primary objective of this study was to assess the feasibility of applying in situ UV spectroscopy in combination with multicomponent analysis (MCA) to simultaneously quantify the dissolution of a drug and its coformer from a cocrystal. A secondary objective was to determine whether this approach can support a mechanistic understanding of cocrystal dissolution. Experimental approach: The rotating-vessel μDISS system equipped with an in situ UV probe was used for dissolution tests. Carbamazepine (CBZ) cocrystals with saccharin, nicotinamide, and 2,4-dihydroxybenzoic acid were used as model compounds. The concentrations of CBZ and each coformer were simultaneously quantified using MCA of the in situ UV spectra. Key results: The concentrations of CBZ and the coformer were successfully quantified by MCA throughout the dissolution process. In the absence of a polymeric precipitation inhibitor (PPI), the dissolution of CBZ from the cocrystal reached only 20%, and no supersaturation was observed, whereas the coformers were rapidly released. In contrast, in the presence of PPIs, the dissolution of CBZ from the cocrystal increased to supersaturated levels, while the dissolution of the coformer decreased. Supersaturation of CBZ was achieved when CBZ and the coformer dissolved congruently. A PPI may interfere with the molecular dissociation of CBZ and the coformer from the cocrystal surface, resulting in a slower release of both CBZ and the coformer. This effect may have reduced the local CBZ concentration at the particle surface and, consequently, slowed the precipitation of CBZ dihydrate on the particle surface. Conclusion: MCA enables the simultaneous quantification of a drug and its coformer from in situ UV spectra during cocrystal dissolution testing. This analytical approach provides valuable insights into the dissolution mechanisms of cocrystals.
Copyright (c) 2026 Shiori Ishida, Samuel Lee, Balint Sinko, Karl Box, Kiyohiko Sugano https://creativecommons.org/licenses/by/4.0
High-sensitivity electrochemical immunosensor for anti-SARS-CoV-2 IgG detection using screen-printed carbon/cerium oxide-gold electrode
Background and purpose: Serological assays are essential for evaluating immune responses, including donor screening, vaccine efficacy, and antibody persistence. However, conventional methods are time-consuming and require centralized laboratories. This study aimed to develop a sensitive and rapid electrochemical immunosensor based on a cerium oxide-gold nanocomposite (CeO₂-Au) modified screen-printed carbon electrode (SPCE) for the detection of anti-SARS-CoV-2 IgG, while elucidating the underlying electrochemical sensing mechanism. Experimental approach: CeO₂-Au nanocomposites were synthesized and characterized using UV-Vis, SEM, TEM-EDX, and FTIR. The immuno­sensor was fabricated by immobilizing SARS-CoV-2 Spike receptor-binding domain (RBD) onto the modified SPCE. Electrochemical responses were evaluated using differential pulse voltammetry (DPV) and electrochemical impedance spectroscopy (EIS) with K₃[Fe(CN)₆] as a redox probe. Key results: The CeO₂-Au nanocomposite enhanced electron transfer and provided a high surface area for biomolecule immobilization. The sensing mechanism is governed by modulation of interfacial electron transfer: binding of IgG to immobilized RBD forms an insulating immunocomplex layer, increasing charge transfer resistance and suppressing faradaic current. The sensor exhibited a wide linear range of 0.01 to 103 ng mL-1, a low detection limit of 2.475 pg mL-1, good stability, and reliable 97.3 to 108.56 % recovery in serum samples. Conclusion: This immunosensor proposed as a sensitive and reliable platform for IgG detection. The study advances understanding of signal transduction mechanisms in nanocomposite-based immunosensors and highlights their potential for rapid serological diagnostics. However, broader clinical validation and selectivity against complex interferents remain necessary.
Copyright (c) 2026 Melania Janisha Devi, Ratu Shifa Syafira, Shabarni Gaffar, Irkham Irkham, Yasuaki Einaga, Yeni Wahyuni Hartati https://creativecommons.org/licenses/by/4.0
Graphene-supported Pd/Pt nano-catalysts for enhanced colorimetric detection of dopamine and NADH using paper-based microfluidic devices
Background and purpose: Dopamine and nicotinamide adenine dinucleotide (NADH) are key biomarkers associated with neurological and metabolic disorders. Developing rapid, low-cost, and portable detection platforms of these biomarkers is essential for a point-of-care diagnostic kit. In this work, we report a colorimetric sensing approach using paper-based microfluidic devices (µPADs) modified with graphene-supported palladium (G/Pd) and platinum (G/Pt) nanocatalysts to enhance detection performance. Experimental approach: Monolayer G/Pd and G/Pt nanocomposites were synthesized via a hydrothermal method with precursor concentrations ranging from 0.1 to 10 mM. The catalytic behaviour and metal-graphene interactions were further investigated using spin-polarized density functional theory (DFT) calculation (PHASE/0). Microfluidic paper-based analytical devices (µPADs) were laser-printed on commercial filter paper and folded into 3D origami structures. Colorimetric responses were quantified using red, green, blue (RGB) and hue, saturation, value (HSV) analysis, where time-dependent Euclidean distance in RGB colour space was used to assess the reaction kinetics. Key results: DFT results indicate that Pd and Pt clusters preferentially adopt a top-site configuration on graphene, facilitating interfacial charge redistri­bution and enhancing catalytic activity experimentally. Catalyst-modified µPADs significantly improve reaction kinetics, reducing detection time by up to 3.7× for dopamine and 2.5× for NADH compared to unmodified devices. G/Pt (10 mM) exhibits the best overall performance, achieving limits of detection of 0.16 µM for dopamine and 0.195 µM for NADH with good linearity (R2 = 0.91). G/Pd displays competitive sensitivity, particularly at lower precursor concentration. Conclusion: The findings highlight that optimizing catalyst morphology and interfacial electronic structure is more critical than minimizing activation energy for achieving high-performance colorimetric sensing. The resulting platform shows potential as a cost-effective and portable tool for the detection of clinically relevant biomarkers in point-of-care settings.
microfluidic paper-based analytical devices
Copyright (c) 2026 Ruri Wahyuono, Jovin Jovin, Ignacius Gilbert Chano, Arda Fridua Putra, Annisa Septyana Ningrum, Muhammad Yusuf Hakim Widianto, Irkham Irkham, Yeni Wahyuni Hartati, Wulan Tri Wahyuni, Isnaini Rahmawati, Chi-Hsien Huang, Yi-Ting Lai 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
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
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