2026-03-06
Dion Notario, Untung Gunawan, Pretty Falena Atmanda Kambira, Erna Wulandari, Eko Adi Prasetyanto
Background and purpose: Mitragynine is an active compound in kratom that is metabolized to the pharmacologically active 7-hydroxymitragynine, requiring an integrated pharmacokinetic approach to maintain plasma concentrations of both within the optimal range. This study aims to develop an integrated pharmacokinetic model of mitragynine and 7-hydroxymitragynine using Bayesian inference. Experimental approach: A secondary dataset of mitragynine and 7-hydroxymitragynine in healthy human plasma was extracted and used to construct a two-compartment pharmacokinetic model upon oral administration. Initial parameter estimation was performed using a deterministic model fit to determine prior parameters. Bayesian inference was performed using Hamiltonian Monte Carlo across four independent chains, each with 2,000 iterations. Key results: The prior distribution estimation indicated that the Markov Chain Monte Carlo chain had converged and attained stationarity, yielding many independent effective samples. In general, no correlation between pharmacokinetic parameters was found due to modelling errors. The posterior predictive check plot confirmed a good fit between the model and the data. Pharmacokinetic simulations of repeated administration have been successfully developed and used to predict essential parameters in repeated administration, such as accumulation factors, maximum plasma concentration, time to maximum concentration, minimum plasma concentration, and area under the curve. Conclusion : The pharmacokinetics of mitragynine and 7-hydroxymitragynine were successfully modelled simultaneously with two compartments and proportional residuals using Bayesian inference with high accuracy.
2026-03-06
Ahmad Fariz Maulana, Sriwidodo Sriwidodo, Iman Permana Maksum, Yaya Rukayadi
Background and purpose: Diabetes mellitus type 2 is a global health issue marked by hyperglycemia and metabolic dysfunction. Despite progress, discovering safe and effective antidiabetic agents remains crucial. This review highlights integrated In Silico, In Vitro, and in vivo methods for identifying novel antidiabetic compounds from natural and synthetic origins. Experimental approach: Computational tools including molecular docking, molecular dynamics, and ADMET prediction identified inhibitors targeting DPP-IV, α-glucosidase, and PPAR. Promising compounds underwent in vitro enzymatic and cellular assays, followed by in vivo efficacy tests in diabetic animal models assessing glucose levels, biochemical markers, and tissue histopathology. Key results: Integrated computational and experimental approaches effectively pinpointed compounds with strong target binding, enzyme inhibition, and positive cellular effects. In vivo data showed significant glucose reduction, enhanced insulin response, and pancreatic protection. ADMET analysis further supported their drug-likeness and safety profiles. Conclusion : Combining computational screening with biological validations forms a cost-effective pipeline for antidiabetic drug discovery. Multi-disciplinary integration increases lead identification success, guiding future refinement of in silico models and expanded in vivo studies to accelerate novel diabetes therapeutic development.
2026-03-06
Parami Sinhapitiya, Samawansha Tennakoon, Isuri A. D. K. Weeraratne
Background and purpose: The development of antimicrobial resistance reduces the efficacy of antimicrobial agents and poses a significant challenge to treat skin diseases. Many scientists, researchers, and pharmaceutical companies work diligently to investigate novel antimicrobial agents and discover alternatives to existing ones, aiming to address antimicrobial resistance. Within the broad field of metal complexes, Schiff base complexes occupy a prominent position, with structural versatility and significant biological properties that make them promising candidates for developing alternative drugs to combat the global crisis of antimicrobial resistance. Experimental approach: This paper reviewed the existing literature on how the structural features of some recently studied Schiff base ligands and their complexes influence the antibacterial and antifungal activities of these compounds against common skin pathogens, including Candida albicans sp., dermophytes, Staphylococcus aureus and Streptococcus pyogenes . Key results: The structural features, including the azomethine group (C=N), heteroatoms and substituents, in Schiff base compounds have been associated with interference with protein synthesis and the growth of bacterial and fungal cells. Schiff base compounds affect cell wall and cell membrane synthesis and inhibit enzymes essential to cell division and other cellular mechanisms. The chelation theory and the overtone’s concept suggest that Schiff base metal complexes exhibit higher antibacterial and antifungal activities compared to Schiff base ligands. Conclusion: This review focuses on providing an overview of how the structural features of Schiff base compounds influence the antimicrobial properties of these compounds against Candida albicans sp., dermophytes, S taphylococcus aureus and Streptococcus pyogenes .
2025-12-02
Hitendra Mahajan, Ghanshyam Girnar
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 : Nanoemulsions were developed using high-pressure homogenization and optimized by adjusting surfactant mixture ratios and homogenization cycles. Characterization included droplet size (<200 nm), polydispersity index, zeta potential, drug content, transmission electron microscopy (TEM), and drug release profiles. Intranasal suitability was assessed through in vitro, ex vivo and in vivo studies, including pharmacokinetics, single photon emission computed tomography (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 (C max = 67.79 ng mL -1 intranasal vs. 49.71 ng mL -1 intravenous). 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.
2025-12-02
Erfan Jafari Sale, Mohammad Satari, Behnam Hajipour-Verdom
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.
2025-10-21
Ali Obaid Imarah, Nada Hasan, Mustafa G. Alabbasi
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.
2025-10-06
Maria Freitas, Vitória Dibo, Rita Ribeiro, Cristina Delerue-Matos, Simone Morais, Álvaro Torrinha
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.
2025-09-26
Sharmila Battira Madappa, Jamballi G. Manjunatha
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 cm 2 , 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.
2025-08-24
Suyarta Efrida Pakpahan, Anggraini Barlian, Arie Wibowo, Indra Wibowo
Background and purpose: Traditional diabetic chronic skin wound dressings often lack the bioactivity required to promote regeneration in these complex wounds. The use of human amniotic membrane (hAM) has been identified as a promising natural option for diabetic skin wound regeneration, but hAM is susceptible to rejection and release of growth factors, so cells must be decellularized and supplemented with biomaterials such as spidroin, a hydrogel delivery system. This study aims to analyse and evaluate a composite hydrogel combining hAM and spidroin proteins to enhance the healing of diabetic chronic wounds. Experimental approach: Hydrogels were synthesized and characterized using scanning electron microscope (SEM), attenuated total reflectance Fourier transform infrared spectroscopy, physical tests, gel fraction and swelling ratio. Wound healing studies were performed using alloxan-induced diabetic mice. Full-thickness wounds were created and treated with the hydrogel formulations. Macroscopic progress of wound healing was monitored, and histological analysis was performed to assess reepithelialization, inflammatory response, and collagen deposition. Key results: The functional groups of hAMD components were identified at the characteristic absorption peaks of 1650 cm⁻¹, while spidroin showed a peak at 1530 cm⁻¹. In particular, the 10 % composite (hAMD + spidroin) showed significantly faster wound closure compared to the control group and other treatment groups. Histological findings confirmed that the 10 % composite was able to facilitate cell proliferation, reduce inflammation, enhance epithelial regeneration, angiogenesis, fibroblast formation and regular collagen matrix and decrease transforming growth factor beta in the remodelling phase. Conclusion: Composite (hAMD + spidroin) 10 % showed promising wound healing efficacy in diabetic conditions, indicating its potential as a bioactive wound dressing for chronic diabetes.
2025-08-04
Alka Singh, Ansab Akhtar, Prashant Shukla
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.
2025-01-03
Anbazhagan Thirumalai, Koyeli Girigoswami, Karthick Harini, Venkatakrishnan Kiran, Pazhani Durgadevi, Agnishwar Girigoswami
Background and purpose : Despite significant advancements in cancer therapies, chemotherapeutics continue to be the mainstay for treating cancer patients, with 5-fluorouracil (5-FU) being commonly used for various cancers. However, its limited ability to penetrate cell membranes and its short half-life, caused by rapid metabolism, necessitate frequent administration of high doses to maintain effective therapeutic levels. This study aimed to synthesize oxidized sodium alginate (OSA) derivatives to create OSA nanoparticles loaded with 5-FU (OSANP@ 5-FU), promoting diketo tautomers, and evaluate their photophysical properties, release profile, and anticancer activity with minimal toxicity. Experimental approach: The investigation encompassed physicochemical characterization, encapsulation efficiency, 5-FU release kinetics at pH 2.2 and 7.4, cell viability assessment via MTT assay in V79 cells, and in vitro anticancer efficacy in the A375 cell line. Key results: Steady-state absorption and emission confirmed the presence of advantageous diketone tautomers of 5-FU, indicating radiative transitions from the second singlet excited state to the ground state (S2S0) and the drug's encapsulation within the polymeric nanostructure. Dynamic light scattering revealed that OSA nanoparticles, initially 177.8 nm, grew to 226.6 nm after encapsulating 5-FU, retaining high zeta potential for stability. With a 68% encapsulation efficiency, in vitro studies showed 46 to 54 % of 5-FU released across different pH levels within 510 minutes. Conclusion: In acidic conditions, there is a greater release of 5-FU than neutral pH levels, indicating a pH-responsive release profile beneficial for cancer treatment, with the release mechanism of OSANPs following Fickian diffusion as identified by a Korsmeyer-Peppas mathematical model and the formu¬lation showing improved therapeutic efficacy.