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.
Anti-infective macrozones: design, biological evaluation and structure-activity relationships
Background and purpose: To discover novel compounds active against sensitive and resistant bacterial strains, a series of novel azithromycin-thiosemicarbazone conjugates, the macrozones, have been syn­the­sized and their biological activity evaluated with corresponding (quantitative) structure-activity relationship ((Q)SAR) analyses conducted. Experimental approach: A systematic variation of thiosemicarbazone side-chains and coupling at positions 4''-, 3-, and 9a of the azithromycin scaffold has resulted in a novel class of bacterial ribosome inhibitors. Key results: Compared to azithromycin, the activity of 4''-macrozones has shown the greatest improvements against efflux-resistant S. pneumoniae and S. aureus, as well as very good activity of 4'' derivatives against E. faecalis. QSAR calculations indicate that the antibacterial activity of macrozones is primarily determined by the position of the thiosemicarbazone side chain. Among the conjugated derivatives, the 4''-substituted macrozones exhibit the highest overall activity against a range of sensitive and efflux-resistant Gram-positive bacteria, as well as against Gram-negative E. coli strains, while those substituted at 9a- and 3- positions are found to be less potent. The antibacterial activity of macrozones is favourably influenced by larger fractions of their cationic and zwitterionic forms, their capacity for hydrogen bond formation, and the extension of p-electron delocalization involving the thiosemicarbazone moiety. Conclusion: The results obtained provide a sound basis for guiding further medicinal chemistry efforts toward the discovery of more potent macrolide anti-infectives, with particular emphasis on resistant bacteria that pose a serious threat to human health.
Copyright (c) 2026 Tomislav Jednačak, Višnja Stepanić, Iva Habinovec, Ivana Mikulandra, Kristina Smokrović, Hana Čipčić Paljetak, Mirjana Bukvić, Jelena Parlov Vuković, Ivan Grgičević, Leda Divjak, Klaus Zangger, Predrag Novak https://creativecommons.org/licenses/by/4.0
Insights into drug resistance in Leishmania: Mechanisms, therapeutics, and clinical case studies
Background and purpose: Leishmaniasis, a neglected tropical disease caused by the protozoan parasite Leishmania, remains a significant public health concern in endemic regions. The disease manifests in various forms, including cutaneous, mucocutaneous, and visceral leishmaniasis, each associated with specific Leishmania species and influenced by host immune responses. Over the past few decades, treatment for leishmaniasis has relied on a limited range of drugs, including pentavalent antimonials, amphotericin B formulations, miltefosine, and paromomycin. However, widespread drug resistance, particularly in visceral leishmaniasis, has severely compromised treatment efficacy, leading to rising cases of treatment failure. This review aims to provide a comprehensive understanding of the mechanisms underlying drug resistance in leishmaniasis and to highlight the factors that contribute to its development. Experimental approach: The study synthesizes existing literature on resistance mechanisms among anti-leishmanial drugs, focusing on changes in parasite uptake and efflux, intracellular sequestration, and modulation of stress responses. It also examines the impact of environmental factors, such as arsenic exposure in endemic regions, and reviews recent molecular and genomic studies that have identified resistance-associated markers. Conclusion: The review underscores the urgent need for innovative therapeutic strategies and highlights the importance of an integrated approach to combat drug resistance through enhanced surveillance, molecular insights, and global collaboration.
Copyright (c) 2026 Gajala Deethamvali Ghousepeer, Mansi Rani, Aman Kumar, Shubhankar Kumar Singh, Anjali Priyadarshini, Elcio Leal, Shailja Singh, V. Samuel Raj, Subhajit Basu, Ramendra Pati Pandey https://creativecommons.org/licenses/by/4.0
Novel stirring method for small-scale dissolution test: Rotating vessel method
Background and purpose: In the compendial dissolution test, the overhead rotating paddle method (ORP) has been used for stirring, whereas the magnetic stirring bar method (MSB) has been employed for small-scale dissolution tests, such as the μDISS ProfilerTM (μDISS). Previous reports have indicated that differences exist in the precipitation profiles of a drug between ORP and MSB, because the latter causes contact-induced nucleation. However, it has been difficult to use an ORP and an in situ UV probe simultaneously in μDISS. In this study, a novel stirring method, the rotating vessel method (RV), was developed for μDISS. The dissolution and precipitation profiles of model drugs in RV-μDISS were then compared with those in MSB-μDISS, as well as with the results of conventional dissolution tests using an ORP. Experimental approach: In RV-μDISS, a small paddle (approximately 1/4 of the conventional paddle) was fixed to the UV probe, and the glass vessel was rotated to produce a flow pattern similar to that of ORP. The dissolution and bulk-phase precipitation tests were per­formed for ibuprofen sodium (IBU Na) and carbamazepine (CBZ), respectively, using RV-μDISS and MSB-μDISS, as well as ORP with the conventional vessel (500 mL, for IBU Na) (CV) or the mini-vessel (50 mL, for CBZ) (MV). Key results: The dissolution rate of IBU Na was similar in all methods. Rapid precipitation of crystalline IBU free acid was observed in the MSB-μDISS method. In contrast, no crystalline precipitation was observed in RV-μDISS and ORP-CV, and the drug phase-separated as a liquid (oil) phase (liquid-liquid phase separation). The precipitation rate of CBZ in RV-μDISS was similar to that in ORP-MV, but slower than that in MSB-μDISS. Conclusion: The precipitation profile in RV-μDISS was close to those in ORP-CV and ORP-MV. RV-μDISS would be a useful tool for the assessment of the precipitation profiles of drugs.
Copyright (c) 2026 Shiori Ishida, Samuel Lee, Balint Sinko, Karl Box, Kiyohiko Sugano https://creativecommons.org/licenses/by/4.0
Injectable hydrogels for bone regeneration: mechanical reinforcement strategies using nanoparticles and nanofibers
Background and Purpose: The growing demand for bone regeneration following severe injuries highlights the importance of scaffolds in bone tissue engineering (BTE). Injectable hydrogels have emerged as promising candidates because their properties closely mimic the native extracellular matrix (ECM). However, their limited mechanical strength and structural instability restrict their practical application. Approach: This review summarizes recent strategies for reinforcing in situ-forming injectable hydrogels to improve their mechanical performance for bone regeneration. Particular emphasis is placed on nanomaterial-based strategies, including the incorporation of nanoparticles and nanofibers, and their ability to enhance the physical properties of polymeric networks. Key Results: Evidence from recent studies demonstrates that reinforcing hydrogels with nano-scaled materials creates interconnected networks that improve load-bearing capacity, stability, and resistance to deformation. These reinforced systems retain the inherent advantages of injectable hydrogels-biocompatibility, biodegradability, permeability to oxygen and nutrients, and drug delivery capability-while addressing their mechanical shortcomings. Conclusion: Nanomaterial-based reinforcement offers a versatile approach to overcoming the limitations of injectable hydrogels in BTE. By providing improved structural integrity alongside biological functionality, these advanced systems broaden the potential of injectable hydrogels for clinical translation. Future work should focus on optimizing reinforcement strategies to balance mechanical enhancement with safety, manufacturability, and regulatory considerations.
Copyright (c) 2026 Fariba Ganji, Morteza Mirzagoli, Lobat Tayebi https://creativecommons.org/licenses/by/4.0
Potential effect of nanoformulated iota carrageenan in Aβ1-42 disaggregation: an in vitro, in vivo and in silico study
Background and purpose: Alzheimer's disease is the primary contributor to neurodegenerative conditions. These pathologies are identified by the deposition of β-amyloid peptide within brain regions. It develops insoluble fibrils known as senile plaques. These plaques are associated with synaptic dysfunction, neuroin­flammation, and progressive cognitive decline. Hence, the degradation and elimination of β-amyloid peptide fibrils from the body are viable therapeutic approaches for managing Alzheimer’s disease. Experimental approach: In the current study, liposomal nanoformulated iota carrageenan was synthesized and characterized using different photophysical tools. The nanoformulated iota carrageenan effectively degraded β-amyloid peptide 1-42, with 45.5 % reduction confirmed by Thioflavin T fluorescence assay. This activity was further supported by turbidity and dynamic light scattering analysis. Key results: The biocompatibility of nano­form­ulated iota carrageenan and its degraded β-amyloid peptide was determined using an 3-(4,5-dimethylthiazol- -2-yl)-2,5-diphenyltetrazolium bromide (MTT), live/dead cell assay on PC12 cells. Structural disintegration of the β-amyloid peptide fibrils was validated through atomic force microscopy, revealing a significant reduction in fibrillar morphology. In silico studies also evidenced the interaction between the β-amyloid peptide and nanoformulated iota carrageenan. In addition, the neuroprotective potential of nanoformulated iota carrageenan, as evidenced by nanoformulated iota carrageenan-treated β-amyloid peptide, was supported by neurite outgrowth studies. These studies showed that differentiated PC12 cells exhibited larger neurite growth with extensive branching, indicating the reversal of β-amyloid peptide-induced neurotoxicity. CAM assay demonstrated enhanced blood vessel formation in chick embryos treated with nanoformulated iota carrageenan and its β-amyloid peptide-degraded group. Conclusion: These findings suggest that nanoformu­lated iota carrageenan holds potential and has nontoxic therapeutic effects for Alzheimer’s disease. Additional in vivo validation is required in future investigations.
Copyright (c) 2026 Saranya Udayakumar, Sanjay Kisan Metkar, Koyeli Girigoswami, Agnishwar Girigoswami https://creativecommons.org/licenses/by/4.0
Y-Co metal-organic framework for sensitive electrochemical determination of doxorubicin hydrochloride
Background and purpose: Cancer represents a major challenge to public health; therefore, identifying doxorubicin hydrochloride (DOX·HCl) as an important chemotherapy drug holds considerable significance. Experimental approach: An electrochemical sensing strategy was designed for DOX·HCl determination by using Y-Co bimetallic metal-organic framework (Y-Co MOF) modified carbon paste electrode (CPE). The Y-Co-MOF was successfully prepared via the solvothermal method. Key results: Characterizations using field emission scanning electron microscopy, transmission electron microscopy, X-ray diffraction, Fourier transform infrared spectroscopy and energy-dispersive X-ray spectroscopy with elemental mapping images were used to evaluate the morphological features, crystalline structure, functional groups, and elemental composition of the Y-Co-MOF. From cyclic voltammetric studies, well-defined redox peaks of DOX·HCl with improved response peak currents at lower overpotentials were observed on the surface of Y-Co MOF/CPE compared to the unmodified CPE. This indicated that the as-prepared modified CPE has a strong and efficient redox capability toward DOX·HCl. Under the optimized parameters and conditions, the linear response range from differential pulse voltammetry measurements for DOX·HCl were 0.0025 to 100.0 µM, with a low limit of detection of 0.001 µM. Finally, the ability of the designed sensing platform to determine the amounts of DOX·HCl in the injection sample was studied and it has been observed a high and efficient ability with satisfactory values of recovery and relative standard deviation. Conclusion: This analytical approach offers a useful means for the analysis of pharmaceutical formulations, providing potential advantages in cancer therapy.
Copyright (c) 2025 Somayeh Mir, Niloufar Akbarzadeh Torbati, Vahid Amani, Somayeh Tajik, Hadi Beitollahi 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
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
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
Imipramine solubility-pH profiles: self-aggregation vs. common-ion effect
Background and Purpose: The pH-dependent solubility of imipramine (Imp), a tricyclic antidepressant, was investigated in phosphate buffers and chloride-containing aqueous media using the pH-Ramp shake-flask method. It was reported that aggregation of Imp in acidic media and its partial degradation in alkaline media complicate the determination of its solubility. This was further investigated with modified methods. Experimental Approach: For Imp solubility studies, the computer program pDISOL-X was used to design experiments, process data, and refine the equilibrium constants. Isolated solid precipitates under various conditions were characterized using thermogravimetric analysis, differential scanning calorimetry, powder X-ray diffraction, and elemental analysis. The critical micelle concentration (CMC) of ImpHCl was determined in 0.10 M NaH2PO4 and in 0.15 M NaCl by conductometric titrations. Key Results: Detailed analysis of Imp pH-solubility profiles reveal complex equilibria in the aqueous phase and various solid-phase transformations as well. Intrinsic solubility of Imp, solubility products of Imp hydrochloride and Imp phosphate salts, and aggregation constants (trimer, heptamer, and cationic complex with phosphate ions) were determined. Solid state characterization results are in accordance with pDISOL-X analysis. Conclusion: These findings, along with our previous solubility studies of desipramine and nortriptyline, suggest that even subtle structural variations can lead to significant differences in the aqueous media behavior of tricyclic antidepressants. This type of information can be valuable in the early stages of drug discovery, in formulation optimization experiments, as well as in in vitro and in vivo studies.
Copyright (c) 2025 Olivera S. Marković, Miloš P. Pešić, Alex Avdeef, Abu T. M. Serajuddin, Tatjana Verbić 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
Precision therapeutics in non-scarring alopecia: a systemic genomic and pathway-based framework for targeted interventions
Background and purpose: Non-scarring alopecia, principally androgenetic alopecia and alopecia areata is highly prevalent and psychologically burdensome; androgenetic alopecia is androgen-driven, whereas alopecia areata is autoimmune. This review synthesizes genetic architecture and pathway biology to outline a precision framework for targeted interventions. Experimental approach: We reviewed full-text studies from the past decade across PubMed, Web of Science and Google Scholar, applying explicit inclusion/ex­clusion criteria; emphasis was placed on Genome wide association studies and Next generation sequencing findings, immune and androgen-axis biology, environmental modifiers, and therapeutic evidence (conven­tional, targeted, and regenerative), alongside artificial Intelligence-enabled diagnostics. Key results: Andro­genetic alopecia risk converges on androgen-receptor signalling and related loci, with perifollicular inflam­mation and oxidative stress as modifiers; finasteride remains a cornerstone therapy. Alopecia areata reflects polygenic immune dysregulation (e.g. Human leukocyte antigen/cytokine axes) with Janus Kinase-pathway inhibition yielding robust regrowth; across phenotypes, wingless-related integration sit/β-catenin and stem-cell programs are central targets. Regenerative options (Protein Rich Plasma, stem-cell/exosome appro­aches) and artificial Intelligence-assisted stratification are emerging adjuncts. Conclusion: A pathway-guided, genotype and phenotype-informed strategy, targeting the androgen axis for androgenetic alopecia, immune circuits for alopecia areata, and adding regenerative or microenvironmental therapies where indicated-promises earlier diagnosis and more durable, individualized outcomes, especially as genome-wide association study/next-generation sequencing and artificial Intelligence tools are integrated into care.
genome-wide association studies and next-generation sequencing
wingless-related integration sit/beta-catenin signalling pathway
Janus kinase-signal transducer and activator of transcription pathway
Copyright (c) 2025 Rinky Kapoor, Depti Bellani, Raji Patil, Debalina Bose, Madhuri Pola, Prashant Anilkumar Singh, Mamata Mishra, Debraj Shome https://creativecommons.org/licenses/by/4.0
TiO2-embedded molecularly imprinted polymer as electrochemical sensor for ultrasensitive determination of glycopyrronium bromide
Background and purpose: The precise quantification and quality evaluation of glycopyrronium bromide (GLB), a long-acting muscarinic antagonist widely used in the treatment of chronic obstructive pulmonary disease, requires the development of advanced analytical methodologies capable of achieving high sensitivity, accuracy, and selectivity to ensure therapeutic efficacy and formulation integrity. This study aims to overcome the limitations of conventional methods by developing a rapid, cost-effective method for determining GLB. Experimental approach: To achieve this, titanium dioxide nanoparticles (TiO2 NPs) were initially applied onto a glassy carbon electrode surface to provide an enhanced surface area and increased conductivity. Subsequently, a TiO2 nanoparticle-supported molecularly imprinted polymer (MIP) film was synthesized via photopoly­merization using GLB as the template molecule, 4-amminobenzoic acid (4-ABA) as the functional monomer, ethylene glycol dimethacrylate as the crosslinking agent, and 2-hydroxyethyl methacrylate (HEMA) as the basic monomer. Key results: The optimized GLB/4-ABA@TiO2 NPs/MIP- sensor demonstrated outstanding analytical performance, achieving ultra-low picomolar detection limits. The system exhibited superior selectivity (confirmed by high imprinting factor), excellent repeatability and reproducibility, and satisfactory stability. It was successfully applied to the accurate measurement of GLB in both commercial serum and pharmaceutical formulations. Conclusion: The designed nanomaterial-embedded MIP-based electro­chemical system presented here offers a highly successful, sensitive, and selective method for GLB determination. The work significantly advances knowledge in the field of analytical medicine and drug monitoring by providing a fast, robust alternative for routine clinical and quality-control tracking of GLB.
Copyright (c) 2025 Zehra Dogan, Ensar Piskin, Ahmet Cetinkaya, Esen Bellur Atici, Sibel Aysil Ozkan https://creativecommons.org/licenses/by/4.0
Poly(lactic-co-glycolic acid) nanoparticles and microparticles for peptide delivery: release mechanisms and controlling factors
Background and purpose: Therapeutic peptides offer high potency but are limited by rapid degradation, poor bioavailability, and the need for frequent dosing. Poly(lactic-co-glycolic acid) (PLGA) nanoparticles and microparticles are effective carriers capable of protecting peptides and enabling controlled release. This review summarizes the mechanisms governing peptide release from PLGA particles and identifies formulation factors critical for optimizing therapeutic performance. Approach: A comprehensive analysis of polymer charac­teristics, particle design parameters, peptide physicochemical properties, and formulation strategies was conducted using data from recent studies. Release mechanisms, including diffusion, polymer degradation, and erosion, were examined alongside manufacturing methods. The review also evaluates clinical PLGA-based peptide products to highlight translational relevance. Key results: Peptide release profiles are strongly influenced by PLGA molecular weight, lactide:glycolide ratio, particle size, end-group chemistry, drug loading, and excipients. Lower polymer molecular weight, higher glycolide content, and smaller particle dimensions accelerate release, whereas cationic peptides experience electrostatic retention within degrading matrices. Additives such as PEG, magnesium salts, and chitosan coatings effectively modulate burst release and stability. PLGA systems typically display triphasic release profiles governed by diffusion and erosion. Several PLGA microparticle-based peptide depots have achieved clinical success, although no nanoparticle-based products have yet reached the market due to manufacturing and regulatory challenges. Conclusion: PLGA nano- and microparticles provide versatile, tuneable platforms for sustained peptide delivery. Under­stand­ing the interplay between polymer properties, particle architecture, and peptide characteristics is essential for designing next-generation long-acting formulations with improved efficacy and clinical translation.
Copyright (c) 2025 Mohammadmahdi Eshaghi, Marzieh Dehghani, Azam Abedi, Mehrdad Moosazadeh Moghadam , Ramezan Ali Taheri 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
Electrochemical detection of chloramphenicol using gadolinium tungstate with sulphur-doped carbon nitride nanocomposite
Background and purpose: Chloramphenicol (CAP) is a broad-spectrum antibiotic whose unregulated presence in pharmaceuticals and food products raises significant health concerns, underscoring the need for rapid, reliable detection methods. This study aimed to develop a sensitive and economical electrochemical sensing platform based on a novel gadolinium tungstate (Gd2(WO4)3) and sulphur-doped graphitic carbon nitride (S-g-C3N4) nanocomposite for the efficient determination of CAP. Experimental approach: The Gd2(WO4)3/S-g-C3N4 nanocomposite was synthesized via a simple co-precipitation method and characterized using XRD, XPS, EDS, and TEM to confirm structural and morphological integration. A glassy carbon electrode modified with the composite was evaluated by cyclic and linear sweep voltammetry, along with analyses of interference, repeatability, stability, and real samples in eye-drop formulations and milk. Key results: The modified electrode exhibited significantly enhanced electrocatalytic oxidation of CAP compared with bare and individually modified electrodes, demonstrating high sensitivity, good selectivity against common interferents, and strong operational stability and reproducibility. A low detection limit was achieved, and the electrode effectively quantified CAP in real matrices with satisfactory recovery. Conclusion: The findings establish the Gd2(WO4)3/S-g-C3N4 nanocomposite as an efficient sensing material, offering a reliable, stable, and cost-effective platform for routine monitoring of antibiotic residues. While minor optimization may further expand its applicability, the study advances electrochemical sensing by introducing a robust nanocomposite with improved analytical performance for CAP detection.
Copyright (c) 2025 Trishul Alanahally Mallu, Gagankumar Sakleshpur Kumar, Santhosh Arehalli Shivamurthy, Nalini Seetharamaiah, Manoj Kumar Basavarajappa, Sandeep Shadakshari https://creativecommons.org/licenses/by/4.0
Liposome-mediated gene delivery: A comprehensive review of biophysical parameters, lipid composition and targeting strategies
Background and purpose: Gene therapy has emerged as a transformative strategy for treating genetic and acquired disorders, but its clinical success relies heavily on the development of safe, efficient, and target-specific delivery vectors. Experimental approach: The paper systematically analysed published evidence on liposome composition, physicochemical behaviour, targeting strategies, and their applications in delivering diverse nucleic acids, with emphasis on the structure-function relationships of lipid components and the impact of biophysical parameters on transfection efficiency. Key results: Current findings demonstrate that the molecular architecture of cationic, neutral, and anionic lipids, particularly variations in head groups, linkers, and hydrophobic tails, strongly dictates liposome stability, cellular uptake, and cargo release. Biophysical attributes such as vesicle size, zeta potential, membrane fluidity, fusion capacity, and PEGylation were identified as major determinants of in vivo fate. Active targeting through ligands, including antibodies, peptides, folate, and aptamers, enhances cell-specific delivery, while combinatorial approaches with physical enhancement techniques such as sonoporation and electroporation further improve nucleic acid transport. Conclusion: By integrating structural, functional, and application-based insights, this review highlights key design principles for optimizing next-generation liposomal vectors, although challenges remain in achieving consistent in vivo performance and clinical translation. The work advances the field by offering a unified framework to guide rational engineering of liposomal platforms for gene therapy.
Copyright (c) 2025 Erfan Jafari Sale, Mohammad Satari, Behnam Hajipour-Verdom https://creativecommons.org/licenses/by/4.0
Intranasal Carvacrol Nanoemulsion: Stroke Imaging and Neuroprotective Study
Background and Purpose: Cerebral ischemia causes neuronal damage due to restricted blood flow and presents significant challenges for brain-targeted drug delivery because of the blood–brain barrier. The purpose of this study is to formulate and evaluate an intranasal oil-in-water nanoemulsion of Carvacrol, a neuroprotective agent, for direct nose-to-brain delivery in treating cerebral ischemia. Experimental Approach: Nanoemulsion was developed using high-pressure homogenization and optimized by adjusting Smix ratios and homogenization cycles. Characterization included droplet size (<200 nm), PDI, zeta potential, drug content, TEM, and drug release profiles. Intranasal suitability was assessed through in vitro, ex vivo, and in vivo studies, including pharmacokinetics, SPECT imaging, and evaluation in a middle cerebral artery occlusion rat model. Key Results: The optimized nanoemulsion showed sustained release, enhanced nasal permeation, and significantly improved brain bioavailability (Cmax: 67.79 ng/mL intranasal vs. 49.71 ng/mL IV). Lower systemic exposure and high targeting indices (DTE: 1317%; DTP: 92.40%) confirmed efficient brain delivery. SPECT imaging validated localized uptake, and the ischemia model demonstrated strong neuroprotective efficacy. Conclusion: Intranasal Carvacrol-loaded nanoemulsion is a promising non-invasive strategy for cerebral ischemia treatment, enabling effective brain targeting and significant therapeutic benefit.
Copyright (c) 2025 Hitendra Mahajan, Ghanshyam Girnar https://creativecommons.org/licenses/by/4.0
Hypotension and antiphlogistic potential of empagliflozin ocular film: swelling and release kinetics
Background and Purpose: Empagliflozin (EMP) is a sodium-glucose cotransporter 2 (SGLT2) inhibitor used for the management of type 2 diabetes mellitus. The danger of glaucoma in type 2 diabetes mellitus patients is known to be reduced using SGLT2 inhibitors. Empagliflozin is also believed to reduce the level of inflammatory markers. The present work has been undertaken for monitoring intraocular pressure and anti-inflammatory activity using the empagliflozin ocular film formulation. The effect of colloidal silicon dioxide upon the dynamics of swelling and drug release performance was also studied. Experimental Approach: Hydroxypropyl methylcellulose-based ocular film of empagliflozin was prepared, including silicon dioxide in different ratios as 1:0.00, 1:0.01, 1:0.02, 1:0.04, and 1:0.06 (namely, EMA0, EMA1, EMA2, EMA3 and EMA4, respectively) using casting and solvent evaporation. Swelling and drug release studies of the films were conducted in phosphate buffer solution (pH 7.4), and the kinetic mechanisms of swelling and drug release were evaluated. Intraocular pressure was measured after application of the film in the normotensive rabbit eye. Moreover, the anti-inflammatory effect was assessed using a rabbit ocular carrageenan-induced inflammation model. Key Results: Swelling behaviour followed Fickian mechanism in the order: EMA3<EMA2<EMA0<EMA4<EMA1, and partial relaxation with EMA3. Films containing silicon dioxide showed faster release than those without it (EMA0), following a diffusion pattern. The silicon dioxide-loaded film (EMA3) showed significantly lowered intraocular pressure and promising ocular anti-inflammation with favourable binding affinities of EMP to Interleukin-1β, Interleukin 6 and tumour necrosis factor-α. A good correlation between intraocular pressure and drug release was also established. Conclusion: A hydroxy­pro­pyl methylcellulose-based ocular film containing empagliflozin and silicon dioxide could be used to manage intraocular pressure and inflammation in a controlled manner in patients with type 2 diabetes mellitus.
Copyright (c) 2025 Subrata Mallick, Tanisha Das, Sourajit Parida, Mouli Das , Rakesh Swain , Sk Habibullah 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
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
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
Pembrolizumab in PD-L1-positive advanced non-small cell lung carcinoma: A meta-analysis of survival benefits and immune-related toxicity events patterns
Background and objective: Pembrolizumab has shown significant therapeutic benefit in advanced non-small cell lung cancer (NSCLC), but it remains uncertain which patients will benefit the most, and recent data suggest that programmed death-ligand 1 (PD-L1) expression as a single predictive biomarker is insufficient. This systematic review and meta-analysis looked at the safety and efficacy of pembrolizumab in PD-L1-positive advanced NSCLC patients, with a particular focus on disparities in treatment response to PD-L1 level of expression and demographic characteristics. Method: According to the PRISMA 2020 guidelines, six large databases were searched up to March 2025 for randomized controlled trials comparing pembrolizumab with chemotherapy in patients with such conditions. Overall survival (OS) and progression-free survival (PFS) were chosen as primary outcomes, and overall response rate (ORR) and safety profiles as secondary endpoints. A meta-analysis was conducted using a random-effects model, and the Cochrane risk of bias (ROB2) tool was employed to evaluate study quality. Seven randomized controlled trials involving 4,900 patients were included in the analysis. Key results: Pembrolizumab had a substantially better performance compared to chemo­the­rapy for all the measures of efficacy: OS (hazard ratio (HR) 0.65, 95 % confidence interval (CI): 0.57 to 0.73, P < 0.00001), PFS (HR 0.55, 95 % CI: 0.42 to 0.72, P < 0.0001) and ORR (relative risk 2.10, 95 % CI: 1.51 to 2.93, P < 0.0001). Subgroup analysis showed greater survival benefit in patients younger than 65 years (OS HR 0.55) compared to patients aged 65 and older (OS HR 0.72), and in females (OS HR 0.44) compared to males (OS HR 0.67). Of most significant importance, those with PD-L1 expression <1 % also saw considerable benefit in survival (OS HR 0.60), casting doubts over the existing biomarker-based selection criteria. Conclusion: In conclusion, pembrolizumab achieves clinically meaningful survival benefits and an acceptable toxicity in PD-L1-positive advanced NSCLC. The high efficacy observed even in low PD-L1 expressers, and demographic differences in drug response, suggest that existing patient selection criteria could potentially be extended. These findings justify the application of a more advanced approach involving multiple biomarkers for more precise treatment allocation.
Copyright (c) 2025 Alendra Chakramurty, Adetya Rahma Dinni, Ihda Silvia, Aprilyan Laras Cantika, Citrawati Dyah Kencono Wungu 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
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.
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
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