Curr. Pharm. Des. [JOURNAL]
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200 papers
Integrated Network Pharmacology and Molecular Modeling Reveal Therapeutic Potential of Silybum marianum Compounds against NAFLD.
Wang H, Li Y, Guo L … +4 more , Li J, Ni Y, Chen L, Cai D
Curr Pharm Des · 2026 Mar · PMID 41832676 · Publisher ↗
INTRODUCTION: Non-alcoholic fatty liver disease (NAFLD) is a global health burden lacking effective pharmacological treatments. Silybum marianum, a hepatoprotective herb, contains flavonolignans with potential therapeuti...
INTRODUCTION: Non-alcoholic fatty liver disease (NAFLD) is a global health burden lacking effective pharmacological treatments. Silybum marianum, a hepatoprotective herb, contains flavonolignans with potential therapeutic effects against NAFLD, yet its active components and mechanisms remain unclear. METHODS: Active compounds were screened using TCMSP and literature data based on oral bioavailability (OB ≥ 30%) and drug-likeness (DL ≥ 0.18). Putative targets were predicted via SwissTargetPrediction and intersected with NAFLD-related genes from GeneCards, OMIM, and DisGeNET. Key targets were identified through the PPI network and GO/KEGG enrichment analyses. Core compounds were further evaluated by molecular docking (Discovery Studio 2019) and molecular dynamics simulations (GROMACS 2021.4). RESULTS: A total of 33 active ingredients and 132 overlapping targets were identified. Network and pathway analysis revealed AKT1 and MTOR as central proteins involved in insulin signaling, autophagy, and lipid metabolism. Molecular docking showed strong binding affinities of silybin A and silandrin to AKT1 and MTOR, respectively. MD simulations confirmed superior structural stability and compactness of these complexes, with favorable RMSD, RMSF, Rg, SASA, and H-bond profiles. DISCUSSION: Silybin A and silandrin demonstrated stable interactions with key NAFLD targets, modulating lipid metabolism, oxidative stress, and autophagic pathways. These compounds outperformed other flavonolignans in network centrality, binding strength, and dynamic stability, highlighting their potential for further drug development. CONCLUSION: This integrative study provides a mechanistic basis for the anti-NAFLD activity of Silybum marianum, identifying silybin A and silandrin as promising scaffolds for AKT1 and MTOR-targeted therapy.
Evaluation of Microbial Efficacy of Silver-Containing Wound Dressings: Standardized Approach for Addressing Emerging Microbial Threats.
Agarwal A, Mazumder A, Salahuddin
Curr Pharm Des · 2026 Mar · PMID 41832675 · Publisher ↗
INTRODUCTION: Effective wound management is crucial, especially during outbreaks of new microorganisms or antibiotic-resistant strains. Developing new wound dressings can be impractical due to time and cost constraints,...
INTRODUCTION: Effective wound management is crucial, especially during outbreaks of new microorganisms or antibiotic-resistant strains. Developing new wound dressings can be impractical due to time and cost constraints, and redesigning existing products poses significant challenges. Therefore, evaluating the effectiveness of current wound dressings is essential. This study aims to assess the antibacterial properties of existing wound dressings without altering their design. Its objective is to present a systematic, design-agnostic approach for quantifying antimicrobial activity against a range of pathogens, including Gram-positive and Gram-negative bacteria, yeasts, and fungi, providing a framework for organizations to validate their wound dressings against emerging microbial threats. Unlike prior studies, this work integrates AI/ML-based predictive modeling validated with experimental data, offering a forward-compatible tool for evaluating dressing efficacy in a rapidly evolving microbial landscape. METHODS: A comprehensive methodology was employed to evaluate the antibacterial properties of silvercontaining wound dressings in both elemental and ionic forms. Drug release was quantified over 96 hours using a Franz diffusion cell, microwave-assisted digestion, and cloud point extraction, Inductively Coupled Plasma Mass Spectrometry (ICP-MS) quantified silver content. Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC) were determined for pathogens like Candida albicans, Methicillin-Resistant Staphylococcus aureus (MRSA), Vancomycin-Resistant Enterococci (VRE), Klebsiella pneumoniae, and Mucor racemosus, according to Clinical and Laboratory Standards Institute (CLSI) guidelines. Additional metrics included colony count and absorption-based antimicrobial tests, barrier penetration assays, and biofilm disruption. Physiological performance was assessed through biocompatibility testing, Water Vapor Transmission Rate (WVTR) testing, visual degradation studies, and ISO-based shelf-life stability testing. A prototype AI/ML model based on Random Forest regression was trained and validated using fivefold cross-validation to predict microbial log reduction from MIC, MBC, and pathogen species, supporting future data-driven screening strategies. RESULTS: Results showed sustained silver release, high biocompatibility, significant biofilm disruption, and barrier function against microbial infiltration. The AI/ML model achieved high predictive accuracy (R² = 0.8177), validating its potential as a decision-support tool. DISCUSSION: This integrated methodology demonstrated the feasibility of evaluating antimicrobial efficacy across multiple pathogens without altering existing product design. The integration of AI/ML modeling provides predictive insights that closely align with experimental outcomes, suggesting a powerful tool for rapid screening. CONCLUSION: This study provides a robust, scalable framework for evaluating wound dressings. It enhances preparedness for microbial threats, reduces reliance on new product development, and enables evidence-based product validation using predictive and psychologically relevant testing approaches.
Exploring Quantum Dots for Diagnosis and Treatment of CNS Disorders: Toxicity, Biodistribution, and Emerging Challenges.
Sharma KK, Durgapal S, Pandey BS … +4 more , Rastogi V, Kumar P, Kukreti G, Kumar G
Curr Pharm Des · 2026 Mar · PMID 41832674 · Publisher ↗
Researchers are in a continual quest for advanced nanotechnology-based delivery systems to revolutionize the field of brain targeting. Nanotechnology has special significance for drug candidates failing therapeutically d...
Researchers are in a continual quest for advanced nanotechnology-based delivery systems to revolutionize the field of brain targeting. Nanotechnology has special significance for drug candidates failing therapeutically due to their low solubility, permeability, and stability in different physiological environments. They provide the right platform for the enhancement of the bioavailability of drug molecules via controlled release and proper targeting. Recently, quantum dots, the nanoparticles composed of fluorescent semiconducting materials, are gaining much popularity among researchers because of their promising multipronged approach due to numerous unique characteristics such as high surface area owing to their nanosize, fluorescence intensity, photoluminescence, optical and electrical properties, targeting capabilities, high quantum yield, high drug encapsulation efficiencies, high biological membrane permeability capacities, and photostability. Quantum dots possess immense potential for targeting drugs and diagnostic molecules to the site of interest by permeating the blood-brain barrier (BBB), which is the main obstacle for brain delivery. Furthermore, the effectiveness of this nanosystem increases manyfold as compared to its existing counterparts due to its multifunctional approaches of maximizing drug targeting, imaging, and diagnosis to fulfill the purpose of BBB permeation, visualizing brain structures, and monitoring drug delivery patterns for effective treatment of brain disorders. This review focuses on the discussion of the blood-brain barrier as a major obstacle, quantum dots as emerging tools for imaging and targeting, and their recent developments with a special emphasis on toxicity aspects, their biodistribution, challenges, and future prospects.
The Effect of Wei Nai An Capsule on Acute Myocardial Ischemia Complicated with Chronic Atrophic Gastritis via Inflammatory Pathways.
Dai W, Zeng H, Chai X … +7 more , Cai K, Luo A, Wang R, Liu S, Huang Q, Ning N, Nie H
Curr Pharm Des · 2026 Mar · PMID 41832673 · Publisher ↗
INTRODUCTION: Cardiovascular Diseases (CVDs) and Gastrointestinal Disorders (GIDs) show significant comorbidity. We established a rat model of chronic atrophic gastritis (CAG) complicated by acute myocardial ischemia (AM...
INTRODUCTION: Cardiovascular Diseases (CVDs) and Gastrointestinal Disorders (GIDs) show significant comorbidity. We established a rat model of chronic atrophic gastritis (CAG) complicated by acute myocardial ischemia (AMI) to investigate the protective effects and mechanisms of Wei Nai An Capsule (WNAC) on CAG and AMI. METHODS: Potential mechanisms were predicted by using network pharmacology and GEO database analysis. To model CAG, we combined intragastric administration of alcohol, sodium deoxycholate, and ammonia. Injections of β-adrenergic agonist isoproterenol modeled the AMI. Histopathological observations were performed, and gastric pH, cardiac marker enzyme levels, cardiac electrical activity, and mRNA expression in the animals were monitored. RESULTS: Network pharmacology and GEO database analyses suggested that WNAC's positive effect on acute myocardial ischemia complicated by chronic atrophic gastritis is associated with the PI3K-AKT signaling pathway. In the model of acute myocardial ischemia complicated by chronic atrophic gastritis, WNAC significantly decreased the elevated ST-segment on the electrocardiogram, reduced gastric pH, reduced levels of markers of cardiac injury, and reduced the mRNA expression of IκBα, PI3K, NF-κB-p65, and COX2 in cardiac and gastric tissues. DISCUSSION: This study demonstrated the crucial need to suppress pro-inflammatory pathways in the treatment of the comorbidity between CVDs and GIDs. However, additional experiments could further strengthen the causal inference. CONCLUSION: This research indicated that WNAC can be successfully implemented to treat the comorbidity of CVDs and GIDs and provides strong evidence for the discovery of new indications of WNAC in clinical practice.
Alzheimer's Disease, Circadian Rhythms, and the Immune System: Potential Interconnections.
Haddadi A, Heidari A, Rezaei N
Curr Pharm Des · 2026 Mar · PMID 41832672 · Publisher ↗
Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder, marked by the accumulation of amyloid-β plaques and neurofibrillary tangles. Its incidence is rising as the global population ages. This narrativ...
Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder, marked by the accumulation of amyloid-β plaques and neurofibrillary tangles. Its incidence is rising as the global population ages. This narrative review explores the emerging interconnections among AD, circadian rhythms, and the immune system. The circadian system, governed by endogenous clocks, regulates key physiological processes and exhibits disruptions in the early stages of AD. Chronodisruption, disturbance of circadian rhythms, has been implicated in AD pathogenesis through its effects on metabolism, sleep, and neuroinflammation. The immune system also plays a central role in AD, with microglia and astrocytes contributing to disease progression. Immune function displays circadian variation, and disruptions in sleep and circadian timing may impair immune responses, promote inflammation, and compromise amyloid-β clearance. Therapeutic strategies targeting circadian regulation, including melatonin agonists and orexin receptor antagonists, may help mitigate cognitive decline. Additionally, the gut microbiome, modulated by circadian and sleep patterns, has emerged as a potential contributor to AD pathophysiology. This review also highlights interventions that support immune health, such as the Mediterranean diet, antiviral therapies, and physical activity, which may collectively attenuate AD risk. Finally, the bidirectional relationship between immune signaling and circadian rhythms, evidenced by immune modulation of clock genes, underscores a complex, integrated regulatory network. Understanding these interrelated systems may uncover novel approaches for prevention and treatment. By elucidating these interconnections, this review aims to shed light on novel therapeutic strategies and interventions that address multiple facets of the disease, offering potential avenues to improve outcomes for individuals with AD.
Strategic Integration of Electronic Quality Management Systems with Quality Risk Management: Advancing Pharmaceutical Compliance and Operational Excellence.
Chauhan SB, Singh I, Gaur R … +1 more , Jain C
Curr Pharm Des · 2026 Mar · PMID 41832671 · Publisher ↗
The pharmaceutical sector requires strong and flexible quality systems to achieve operational excellence and regulatory compliance. Integrating Quality Risk Management (QRM) frameworks with Electronic Quality Management...
The pharmaceutical sector requires strong and flexible quality systems to achieve operational excellence and regulatory compliance. Integrating Quality Risk Management (QRM) frameworks with Electronic Quality Management Systems (EQMS) provides a transformative approach to quality management across the pharmaceutical value chain. This paper investigates how EQMS and QRM can work together to promote proactive compliance, reduce process variability, and foster a culture of continuous improvement. While QRM offers a systematic process for identifying, evaluating, and managing quality risks throughout the product lifecycle, EQMS technologies provide real-time data collection, optimized documentation, automated workflows, and streamlined regulatory reporting. The integration of these systems enhances risk-based decision- making by addressing deviations, non-conformances, and change controls through analytics, trend analysis, and predictive modeling. Current industry practices, regulatory requirements from organizations such as the FDA and EMA, and technological developments that facilitate this integration, such as cloud-based EQMS systems and AI-enabled risk assessment tools, are critically assessed in this article. To demonstrate how integrated systems have facilitated faster time-to-market, reduced compliance gaps, and improved audit readiness, case studies and implementation models are examined. Additional considerations include system validation, user acceptance, and data integrity. Ultimately, EQMS and QRM integration represents a shift from reactive to proactive quality management, in line with ICH Q9 and ICH Q10 principles, positioning pharmaceutical firms to succeed in an increasingly complex and competitive regulatory environment. For stakeholders aiming to enhance quality outcomes through risk-based governance and digital transformation, this evaluation provides a strategic framework.
Elucidating the Anti-thrombotic Mechanism of Equiseti hiemalis Herba through Integrated Pharmacology.
Song Z, Hu Y, Xu Y … +5 more , Yang Y, Li Q, Ma Y, Guo X, Yan Z
Curr Pharm Des · 2026 Mar · PMID 41832670 · Publisher ↗
INTRODUCTION: This study systematically elucidates the anti-thrombotic material basis, potential targets, and molecular mechanisms of Equiseti hiemalis herba (EH) using an integrated strategy combining metabolomics, seru...
INTRODUCTION: This study systematically elucidates the anti-thrombotic material basis, potential targets, and molecular mechanisms of Equiseti hiemalis herba (EH) using an integrated strategy combining metabolomics, serum pharmacochemistry, network pharmacology, bioinformatics analyses, and molecular docking. METHODS: Components in the EH decoction were identified by UHPLC-MS. Sixteen normal male SD rats were administered EH to monitor weight and organ indices. Plasma metabolomics were used to analyze differential metabolites and pathways. Blood-absorbed prototype components were identified, and their targets were predicted. Network pharmacology was employed to intersect drug targets with thrombosis-related targets from GeneCards and an independent GEO dataset to identify core therapeutic targets. GO analysis and molecular docking were further used for validation. RESULTS: A total of 138 compounds, including caffeic acid, ferulic acid, and 13-docosenamide, were identified in EH. Administration to rats revealed only slight effects on the liver. EH primarily exerts its effects by modulating fatty acid, amino acid, and nucleotide metabolism. It acts on nine key targets (CA9, MAOA, TYMS, etc.) via 15 active components (gingerol, xanthosine, adenosine, etc.), influencing four pathways (glycine and serine metabolism, ammonia recycling, arginine and proline metabolism, pyrimidine metabolism) to achieve its anti-thrombotic effects. Importantly, the dysregulation of these nine key targets was significantly validated in an independent clinical venous thrombosis cohort from the GEO database. CONCLUSION: This study proposes a multi-component, multi-target, and multi-pathway mechanism for EH against thrombosis and provides strong external clinical evidence supporting the disease relevance of the predicted targets. The findings offer a solid theoretical basis and valuable candidate resources for the future development of EH as an anti-thrombotic drug.
Precision Design in Cancer Treatment: Cucurbitacin E Modulates AMPK, PGK1, and PKM2 to Optimize Radiation Efficacy in Melanoma.
Abdelrhman IG, Hamdy AM, Abdalla Hussein M … +4 more , Emara AA, Mohamed SF, Azmy Boshra S, Atef Mahmoud A
Curr Pharm Des · 2026 Mar · PMID 41832669 · Publisher ↗
INTRODUCTION: Cucurbitacin E (CE), a naturally occurring triterpenoid derived from Cucurbitaceae plants, exhibits potent anticancer activity, particularly against melanoma. Previous studies indicate that CE suppresses me...
INTRODUCTION: Cucurbitacin E (CE), a naturally occurring triterpenoid derived from Cucurbitaceae plants, exhibits potent anticancer activity, particularly against melanoma. Previous studies indicate that CE suppresses melanoma progression by activating AMP-activated protein kinase (AMPK), thereby disrupting metabolic pathways and inducing apoptosis. Despite these findings, the potential synergistic interaction between CE and γ-irradiation in melanoma cell death remains unexplored. OBJECTIVE: This study investigates the combined effects of CE and γ-irradiation on apoptosis in A375 melanoma cells, aiming to uncover the underlying molecular mechanisms. The goal is to develop a novel radiosensitization approach to enhance melanoma treatment efficacy. METHODS: A375 cells were categorized into four groups: untreated control (Group I), CE-only (47.146 μg/mL; Group II), γ-irradiation-only (6 Gy/well; Group III), and combined CE + γ-irradiation (Group IV). Synergistic efficacy was assessed using the Chou-Talalay method. Cell viability and apoptosis were evaluated via MTT assays and Annexin V/PI staining. Gene expression (AMPK, PGK1, PKM2) was analyzed using qPCR, while oxidative stress markers (GSH, GR, SOD, GPx, CAT, MDA), cell cycle regulators (P53, P21, cyclin D1, cyclin E2, cdk2, cdk4), and apoptosis-related proteins (Bax, caspase-3, Bcl-2) were quantified via ELISA. Flow cytometry assessed cell cycle arrest and apoptosis. Molecular docking studies analyzed CE's binding affinity with AMPK, PGK1, and PKM2. RESULTS: CE demonstrated dose-dependent cytotoxicity (IC₅₀ = 47.146 μg/mL). The combination of CE (100 μg/mL) and γ-irradiation (6 Gy/well) significantly reduced A375 cell viability, confirming CE's radiosensitizing role. Combination Index analysis confirmed a synergistic interaction between CE and γ-irradiation (CI = 0.68), enhancing melanoma cell radiosensitivity. Flow cytometry revealed CE-induced G2/M arrest and amplified apoptosis when paired with radiation. Mechanistically, CE upregulated AMPK while suppressing PGK1 and PKM2, inhibiting glycolysis. Oxidative stress markers (MDA, P21) increased, whereas antioxidant enzymes (GSH, GR, SOD, GPx, CAT) and cell cycle proteins (cyclin D1, cyclin E2, cdk2) declined. Apoptosis- related analysis showed elevated Bax and caspase-3 levels, alongside reduced Bcl-2 levels, indicating activation of the intrinsic apoptotic pathway. Molecular docking identified strong binding between CE and AMPK (ΔG = -8.1 kcal/mol), PGK1 (ΔG = -7.7 kcal/mol), and PKM2 (ΔG = -7.9 kcal/mol), validating its direct interaction with metabolic targets. DISCUSSION: CE synergizes with γ-irradiation by disrupting glycolysis, inducing oxidative stress, activating intrinsic apoptosis, and arresting the cell cycle at G2/M. Its dual role as a metabolic inhibitor and radiosensitizer overcomes melanoma's resistance mechanisms. These findings align with prior studies on cucurbitacins but are the first to demonstrate CE's radiosensitizing effects in A375 cells. Limitations include the need for invivo validation. CONCLUSION: CE acts as a potent radiosensitizer, augmenting γ-irradiation-induced apoptosis in A375 cells through metabolic disruption, oxidative stress modulation, intrinsic apoptotic activation, and cell cycle arrest. These results highlight its potential for improving melanoma radiotherapy. Future research should optimize dosing regimens and explore clinical translation to advance precision oncology strategies.
Exploring Key Target Genes of Tong Bian Bai Tou Weng Decoction for Ulcerative Colitis: A Combined Approach of Mendelian Randomization, Network Pharmacology, and Transcriptomics.
Cui C, Jiang JQ, Li ZC … +3 more , Yin XY, Lu YC, Wang ZY
Curr Pharm Des · 2026 Mar · PMID 41832668 · Publisher ↗
INTRODUCTION: Ulcerative colitis (UC) manifests as persistent inflammation and ulceration within the mucosal and submucosal layers of the colon. The present study sought to elucidate the principal targets of Tongbian Bai...
INTRODUCTION: Ulcerative colitis (UC) manifests as persistent inflammation and ulceration within the mucosal and submucosal layers of the colon. The present study sought to elucidate the principal targets of Tongbian Baitouweng Decoction (TBD) in UC. METHODS: A total of 221 TBD-related and 1,270 UC-related genes were retrieved from public databases, with their intersection as candidate targets. Differential expression, machine learning, expression profiling, MR analysis, network construction, molecular docking, enrichment, and immune infiltration analyses were used to refine key targets and explore their functional associations with UC. RESULTS: PPARG, STAT1, and IL1B emerged as the principal targets of TBD against UC. Among UC samples, IL1B and STAT1 were upregulated, whereas PPARG was downregulated. MR analysis revealed significant causal associations: STAT1 (OR = 1.17), IL1B (OR = 0.50), and PPARG (OR = 0.97). A network comprising three targets and 53 corresponding active compounds was established, with molecular docking demonstrating strong binding affinities, particularly with quercetin. Enrichment analysis indicated that the three targets were jointly involved in pathways such as "Toll-like receptor signaling". Immune infiltration analysis revealed that IL1B and STAT1 correlated positively with activated CD4 T cells, macrophages, and natural killer cells, whereas PPARG displayed an inverse pattern. DISCUSSION: These findings align with existing evidence linking STAT1, PPARG, and IL1B to UC pathogenesis, highlighting TBD's therapeutic potential by targeting key inflammatory and barrier-regulatory pathways; future studies should validate these targets in preclinical models and explore the formula's clinical efficacy in large-scale trials. CONCLUSION: STAT1, PPARG, and IL1B were TBD's key UC therapeutic targets, with regulatory roles providing a UC research mechanistic framework.
Multidimensional Data-Driven Mechanistic Insights into Anle Tablets for Depression Treatment through Molecular Docking and Dynamics.
Chen T, Zhang M, Liu R … +5 more , Dong H, Zhao Y, Luan M, Zhang A, Si H
Curr Pharm Des · 2026 Mar · PMID 41820321 · Publisher ↗
BACKGROUND: Depression is a serious mental health problem, leading to low mood, loss of interest, and even extreme behaviors. Anle tablets are commonly used in the clinical treatment of depression; however, their mechani...
BACKGROUND: Depression is a serious mental health problem, leading to low mood, loss of interest, and even extreme behaviors. Anle tablets are commonly used in the clinical treatment of depression; however, their mechanism of action is still unclear. METHODS: Components and targets of Anle tablets were identified using Traditional Chinese Medicine Systems Pharmacology Database (TCMSP), PubChem, and SwissTargetPrediction. Depression-related targets were searched from the Genecards, Online Mendelian Inheritance in Man (OMIM), and the Therapeutic Target Database (TTD). A network diagram was constructed to screen the core components. We conducted enrichment analysis to demonstrate the underlying molecular mechanisms. Feature targets were identified utilizing the Gene Expression Omnibus (GEO), machine learning, and a nomogram. We subsequently performed preliminary validation using molecular docking and another GEO dataset. Finally, we performed a dynamic analysis of drug-target protein binding using molecular dynamics simulations. RESULTS: IGF1R, HSD11B1, GABRA1, and OPRK1 were screened as the feature targets. The core components were screened, such as 3,22-Dihydroxy-11-oxo-delta(12)-oleanene-27-alpha-methoxycarbonyl-29-oic acid (MOL004905), (+)-Anomalin, and 7-Acetoxy-2-methylisoflavone. The primary mechanisms of action were associated with synaptic function and neurotransmitter transmission. The drug component MOL004905 and the target protein HSD11B1 emerged as the optimal docking pair. Their binding sites and the forces of interaction between them revealed strong stability. DISCUSSION: This study employed a multifaceted approach, integrating network pharmacology, bioinformatics, molecular docking, and molecular dynamics simulations, to analyze the components, targets, and mechanisms of Anle tablets in the treatment of depression. It also simulated the combination of drug molecules and target proteins and conducted a comprehensive evaluation. CONCLUSION: Anle tablets may exert their therapeutic effects by targeting feature targets through their core active components, thereby modulating synaptic function and neurotransmitter transmission.
Nanovaccines in Cancer Immunotherapy: Lymph Node-Targeted Strategies and Mechanistic Insights.
Rajni, Gupta R, Shah K … +1 more , Dewangan HK
Curr Pharm Des · 2026 Feb · PMID 41764629 · Publisher ↗
BACKGROUND: Cancer immunotherapy has been a rapidly growing therapeutic approach, with nanovaccines offering new opportunities to improve antigen delivery and activate immune responses. Nevertheless, traditional cancer v...
BACKGROUND: Cancer immunotherapy has been a rapidly growing therapeutic approach, with nanovaccines offering new opportunities to improve antigen delivery and activate immune responses. Nevertheless, traditional cancer vaccines are generally under-immunogenic and ineffective in lymphoid targeting. This article reviews progress in nanotechnology-based vaccine platforms, with a special emphasis on lymph node-targeting nanovaccines for cancer management and therapy. METHODS: We systematically reviewed the recent literature on nanovaccine delivery systems, including liposomes, polymeric nanoparticles, and mRNA-based formulations. The emphasis was on immunological mechanisms, antigen presentation pathways, and lymphatic targeting strategies. RESULTS: Nanovaccines can deliver tumor antigens and adjuvants together to lymphoid tissues, enhancing antigen uptake, dendritic cell activation, and T-cell priming. Systems, such as lipid nanoparticles, artificial dendritic networks, and CpG- or STING-charged nanocarriers, have been shown to exhibit enhanced therapeutic performance in both preclinical and early clinical trials. mRNA-4157 and BNT111 are clinical candidates showing encouraging results in melanoma and other cancer trials. CONCLUSION: Nanovaccine platforms can potentially overcome some constraints of conventional vaccines by enhancing lymph node targeting, antigen stability, and immunogenicity. Further research in this field could further advance targeted cancer immunotherapy.
A Review on Correlation Between Autorefractometer and Cycloplegic Refraction with Subjective Acceptance in Children Aged 6-15 Years.
Fatima A, Rani T, Sai Charan L … +1 more , Dewangan HK
Curr Pharm Des · 2026 Feb · PMID 41764628 · Publisher ↗
INTRODUCTION: Autorefraction is fast, yet accommodation can distort pediatric measurements, and cycloplegic refraction minimizes accommodation and therefore could be more suitable for functional eyesight. The correlation...
INTRODUCTION: Autorefraction is fast, yet accommodation can distort pediatric measurements, and cycloplegic refraction minimizes accommodation and therefore could be more suitable for functional eyesight. The correlation between the readings of the autorefractometer, cycloplegic refraction, and the subjective acceptance was systematically reviewed in children aged between 6 and 15 years. METHODS: Following PRISMA, PubMed, Scopus, and Web of Science were searched (20002024) in search of studies comparing the outcomes of autorefraction, cycloplegic refraction, and/or subjective refraction in children. Risk of bias (QUADAS-2) was assessed using duplicate assessment of eligibility and data extraction. RESULTS: In all the suitable studies, cycloplegic refraction demonstrated the best correlation with the ultimate subjective acceptance and delivered hyperopia estimates that were more accurate in comparison to noncycloplegic cycloplegic autorefractive refraction. Non-cycloplegic autorefraction was more likely to overmyopia/ under-hyperopia in younger children. It was in agreement more when autorefraction was done under cycloplegia and in the old subgroups. DISCUSSION: Since accommodation is dynamic in the pediatric population, non-cycloplegic autorefraction alone is insufficient to misclassify the refractive status. The association of autorefraction with cycloplegia is enhanced in precision and performance, whereas the subjective refinement is fundamental towards comfort and compliance. CONCLUSION: Parents of the 6- to 15-year-old age group children rely most on cycloplegic refraction as a source of prescription, with autorefraction being utilised most optimally under cycloplegia or as a screening measure followed by cycloplegic confirmation and age-adjusted additional subjective refinement.
Transferosomes: A Vesicular Tool for Transdermal Drug Delivery.
Dua A, Mazumder R, Debnath A … +1 more , Mishra R
Curr Pharm Des · 2026 Feb · PMID 41764627 · Publisher ↗
Innovative lipid-based vesicles called transferosomes are designed to improve the delivery of transdermal medications. These ultra-deformable vesicles, comprised of phospholipids and edge activators, can successfully pas...
Innovative lipid-based vesicles called transferosomes are designed to improve the delivery of transdermal medications. These ultra-deformable vesicles, comprised of phospholipids and edge activators, can successfully pass through the skin's stratum corneum and overcome conventional obstacles, resulting in better absorption of medications. Transferosomes have potential uses in treating several illnesses, such as cancer, and various skin ailments, and for vaccine delivery. They are also used to improve the bioavailability of poorly absorbed oral medications. Despite wide applications, the transferosomes formulation approach has limitations in scalability, stability, regulatory approval, and patient compliance, which must be addressed in ongoing and future research to maximize their therapeutic applications and establish transferosomes as a breakthrough in non-invasive drug delivery technology. This review covers the technical aspects involving the composition, structure, mechanisms of action, and formulation approach of transferosomes with comparison to other approaches, which will surely be beneficial for exploring novel targeted approaches involving liposomes, niosomes, ethosomes, and pharmacosomes.
In Silico Identification of Antihypertensive Phytoconstituents in Terminalia arjuna via Molecular Docking, MD Simulation, and DFT Analysis.
Verma P, Sahu SK, Rawat R … +5 more , Eyupoglu V, Patel P, Kaur P, Pandey P, Vyas M
Curr Pharm Des · 2026 Feb · PMID 41764626 · Publisher ↗
INTRODUCTION: Hypertension is a major global health concern, and the exploration of natural compounds as potential antihypertensive agents has been a recent area of study.. The ancient medicinal tree Terminalia arjuna is...
INTRODUCTION: Hypertension is a major global health concern, and the exploration of natural compounds as potential antihypertensive agents has been a recent area of study.. The ancient medicinal tree Terminalia arjuna is very potent for treating cardiovascular conditions. Its bark is rich in bioactive compounds, such as flavonoids, tannins, and triterpenoids, which exhibit cardioprotective properties. METHODS: This research focused on identifying and characterizing antihypertensive phytoconstituents of Terminalia arjuna through molecular docking, dynamic simulations, and DFT studies. We systematically screened bioactive compounds from the plant for their ability to interact with key targets (PDB:2X96), which are involved in the regulation of blood pressure using AutoDock Tools 1.5.7. The dynamic behavior of the complexes was evaluated using molecular dynamics (MD) simulation in the GROMACS package program (version 2022.2). DFT calculations were performed using DMol3 (Discovery Studio Client) to determine molecular electronic properties. RESULTS: We identified Quercetin and Ellagic acid as promising ligands with strong binding affinities and significant pre-ADMET analysis database. Further, molecular dynamics simulations (500 ns) provided insights into the stability and binding modes of these selected compounds, highlighting their potential for long-term efficacy. DFT calculations were employed to evaluate the electronic properties, such as frontier molecular orbital analysis and electrostatic potential mapping, revealing the reactivity and interaction profiles of the compounds. The docking scores and MMGBSA binding free energy value of Ellagic acid with AnCE-RXPA380 complex target protein were found to be -9.5 and -17.94 kcal/mol, respectively, which is higher as compared to Captopril (--5.7 and --4.36 kcal/mol kJ/mol). DISCUSSION: Ellagic acid exhibits more conventional hydrogen binding efficiency at 2X96 receptor with GLN A:361, THR A:364, ASP A:360, LYS A:495, and GLN A:265, respectively, providing a scientific basis for its use in hypertension management Furthermore. CONCLUSION: Our results suggest that Ellagic acid from Terminalia arjuna possesses significant antihypertensive potential due to the highest binding efficiency with 2X96 receptor. However, in vitro, and in vivo experimentation are needed to validate the antihypertensive potential of Ellagic acid in the future.
Breast Cancer Drug Resistance: Precision Targeting of ER and HER2 Signalling Networks.
Kuttiappan A, Chenchula S, Karunakaran PR … +8 more , Talagampala SV, Amerneni LS, Amerneni KC, Gupta SK, Sharma S, Karrothu VV, Bhargavi M, Chavan M
Curr Pharm Des · 2026 Feb · PMID 41764625 · Publisher ↗
Breast cancer (BC) continues to be a significant challenge in oncology, primarily due to the emergence of drug resistance, which severely limits treatment efficacy and adversely affects patient outcomes. This review aims...
Breast cancer (BC) continues to be a significant challenge in oncology, primarily due to the emergence of drug resistance, which severely limits treatment efficacy and adversely affects patient outcomes. This review aims to elucidate the mechanisms underlying drug resistance in BC, focusing on the roles of the estrogen receptor (ER) and human epidermal growth factor receptor 2 (HER2) signaling pathways. It identifies advanced therapeutic strategies that effectively target and overcome resistance by analyzing these pathways. This review integrates a comprehensive selection of clinical data and cell lines with known resistance profiles, encompassing both clinical and laboratory settings. It employs cutting-edge techniques such as highthroughput sequencing, proteomics, and advanced imaging. Key measurements include receptor expression levels, pathway activation states, and drug response data, analyzed using bioinformatics tools for genetic and proteomic insights and statistical models to determine the clinical significance of the findings. The review identifies specific mutations and alterations in the ER and HER2 pathways that contribute to drug resistance. Notably, it highlights novel biomarkers and resistance mechanisms, including the upregulation of alternative signaling cascades and mutations in downstream effectors. It also emphasizes promising targeted therapeutic strategies, such as combination therapies and next-generation inhibitors, which have demonstrated encouraging results in preclinical models. In conclusion, this review provides critical insights into the intricate mechanisms of drug resistance in BC, underscoring the pivotal roles of the ER and HER2 signaling pathways. It identifies unique resistance mechanisms and potential therapeutic targets, paving the way for the development of advanced strategies to improve treatment outcomes.
Polymeric Nanoparticles: Innovative and Promising Tools for Enhanced Cancer Drug Delivery Systems.
Sultan MH
Curr Pharm Des · 2026 Feb · PMID 41764624 · Publisher ↗
Cancers characterized by uncontrolled cell proliferation and metastasis remain a major public health challenge worldwide. In Saudi Arabia, the increasing incidence necessitates comprehensive strategies for prevention, ea...
Cancers characterized by uncontrolled cell proliferation and metastasis remain a major public health challenge worldwide. In Saudi Arabia, the increasing incidence necessitates comprehensive strategies for prevention, early detection, and effective treatment. Drug resistance, often driven by genetic mutations leading to multidrug resistance, remains a major clinical obstacle. The innovative delivery systems such as liposomes, polymeric nanoparticles, and exosomes are required to improve therapeutic efficacy. In this review, data from reputable databases and scientific sources such as Web of Science, PubMed, EMBASE, ScienceDirect, Scopus, and others, are critically compiled and analyzed. Strict inclusion criteria for peerreviewed studies on polymeric nanoparticles in cancer therapy are applied, covering in vitro, in vivo, and clinical applications, while non-English-language, incomplete, or methodologically weak studies are excluded. Biodegradable polymeric nanoparticles such as PLGA, chitosan, and PCL have been shown to improve anticancer drug delivery by enabling precise targeting, reducing systemic toxicity, and overcoming multidrug resistance, with consistent therapeutic benefits observed in all studies. Despite these advances, challenges such as biocompatibility, toxicity, controlled release, tumor heterogeneity, long-term safety, and regulatory hurdles remain unresolved. Overall, nanoparticles represent a promising approach to cancer therapy as they improve drug delivery and minimize side effects, but sustained research and interdisciplinary collaboration are essential to fully exploit their potential in oncology.
Approaches in Skin Cancer Management: Treatment, Early Detection, and Patient-Centric Therapies.
Tripathy S, Shah K, Sarkar R … +1 more , Dewangan HK
Curr Pharm Des · 2026 Feb · PMID 41764623 · Publisher ↗
Skin cancer is the most common cancer globally, and BCCs and CSCCs do comprise most of the non-melanoma skin cancer. The review summarises new epidemiological evidence (2020-2025), indicating the dynamics in global incid...
Skin cancer is the most common cancer globally, and BCCs and CSCCs do comprise most of the non-melanoma skin cancer. The review summarises new epidemiological evidence (2020-2025), indicating the dynamics in global incidence, long-term WHO forecasts to 2050 and the interaction of genes and the environment as risk factors. Pathophysiological understanding highlights molecular modulations, escape from immune attack and the effects of chronic ultraviolet exposure on the development of tumours. The causes and mechanisms of action section has been reorganised and includes detailed mechanistic descriptions of current treatment modalities, such as surgery, radiotherapy, chemotherapy, immunotherapy, and targeted therapy, with examples of clinical applications. Particular emphasis is laid on the clinical treatment of BCC and CSCC in the older adult population, with references to the latest international guidelines and consideration of psychological and social support in treating patients. The new treatment methods emerging, like nanocarrier, photodynamic therapy, and personalised medicine, are addressed with the recent data on their application and future outlook. Under the new section of prevention and patient education, there is an outline of community awareness programs, campaigns aimed at reducing the burden of the sun, early detection, and evidence-based approaches to reduce the disease burden. Other approaches in technical methods are also reviewed to determine their translational opportunities, comprising hyaluronic acid delivery methods, ultrasonic-assisted nanoparticle penetration, and microneedle technology. Current publications have been used massively, and they constitute more than 50 percent of the provided circulatory content, with publications from the last five years, which adds to their clinical nature and timeliness. Bringing together current epidemiology, new treatment approaches, and patient-focused prevention, this review presents a complete evidence-based source to assist clinicians, researchers, and public health staff in managing the emerging era of skin cancer treatment.
Unlocking the Role of Exosomal ncRNAs in Colorectal Cancer: Molecular Insights and Clinical Promise.
Eltaib L, Zhang L, Khan Y … +5 more , Alanazi MN, Elhassan GO, Rana AJ, Maqbool M, Hussain MS
Curr Pharm Des · 2026 Feb · PMID 41764622 · Publisher ↗
Colorectal cancer (CRC) continues to be a substantial cause of cancer-related fatality globally, necessitating improved diagnostic and therapeutic strategies. Exosomes, small extracellular vesicles that facilitate interc...
Colorectal cancer (CRC) continues to be a substantial cause of cancer-related fatality globally, necessitating improved diagnostic and therapeutic strategies. Exosomes, small extracellular vesicles that facilitate intercellular communication, as key mediators in CRC progression by transporting bioactive molecules, including non-coding RNAs (ncRNAs). These exosomal ncRNAs (exo-ncRNAs) participate in regulating gene expression, tumor proliferation, metastasis, chemoresistance, and immune escape. ExoncRNAs show distinct patterns in CRC, making them potential non-invasive indicators for early detection and prognosis. Additionally, the potential of exosome-based therapies, including engineered exosomal RNA delivery, offers new avenues for precision oncology. However, addressing challenges, such as standardization of exosome isolation methods, clinical validation, and mechanistic elucidation, is necessary before their full clinical implementation. This article offers a comprehensive synthesis of the recent knowledge of exo-ncRNAs in CRC, emphasizing their biological functions, molecular mechanisms, and translational potential in diagnostics and therapeutics. Future research integrating artificial intelligence and multi-omics approaches may further enhance the clinical utility of exo-ncRNAs, advancing precision medicine in CRC management.
Exploring 4D Printing Technology for Biomedical Applications.
Ranjan R, Kumar V, Kumar M … +2 more , Kurmi BD, Pal RR
Curr Pharm Des · 2026 Feb · PMID 41742608 · Publisher ↗
As an advancement of 3D printing, 4D printing introduces a time dimension, enabling the fabrication of dynamic, adaptable biological devices. In contrast to stable 3D-printed systems, 4D-printed systems employ intelligen...
As an advancement of 3D printing, 4D printing introduces a time dimension, enabling the fabrication of dynamic, adaptable biological devices. In contrast to stable 3D-printed systems, 4D-printed systems employ intelligent materials, such as shape-memory polymers and hydrogels, that respond to environmental stimuli, such as pH, temperature, and light. Major developments include adaptable implants for applications like tracheal support and cancer therapy, as well as customized, stimuli-responsive hydrogel capsules that enable controlled drug release, thereby enhancing the patient's health, decreasing adverse effects, and increasing accuracy. Nevertheless, several challenges remain, specifically in managing degradation rates, ensuring biocompatibility, and optimizing material selection for clinical studies. As research continues, 4D bioprinting is anticipated to become the main tool for creating personalized, efficient, and adaptive biomedical systems, thereby changing the face of future healthcare and treatment methods. This editorial provides an overview of innovative approaches and demonstrates the importance of 4D printing in the medical field. It highlights the crucial role of 4D printing over 3D printing by incorporating the time dimension, making the resulting devices dynamic and adaptive rather than static. These smart features of the innovative 4D-printed tool have led to significant advancements in medical applications, including customized tracheal support implants and personalized drug-delivery capsules.
Khamira Gaozaban Sada, a Low-Cost Unani Preparation, Alleviates Isoproterenol and L-NAME-Induced Augmented Cardiac Workload.
Shaharyar MA, Bhowmik R, Sarkar A … +10 more , De A, Mandal A, Tiwari V, Chakraborty S, Banerjee SK, Akhtar J, Ayyoob M, Roshan S, Bala A, Karmakar S
Curr Pharm Des · 2026 Feb · PMID 41742607 · Publisher ↗
INTRODUCTION: Cardiac hypertrophy, often a maladaptive response to sustained cardiac workload, can lead to heart failure and increased mortality. Traditional Unani formulation Khamira Gaozaban Sada (KGS) is evaluated for...
INTRODUCTION: Cardiac hypertrophy, often a maladaptive response to sustained cardiac workload, can lead to heart failure and increased mortality. Traditional Unani formulation Khamira Gaozaban Sada (KGS) is evaluated for its cardioprotective effects in preclinical models. The objectives are to assess the efficacy of KGS in reducing cardiac workload and preventing pathological remodeling in L-NAME-induced hypertension and isoproterenol (ISO)-induced cardiac hypertrophy models, and to identify its underlying mechanisms and safety profile. METHODS: Two doses of KGS (1000 and 2000 mg/kg b.w.) were administered in L-NAME and ISO-induced rat models. Hemodynamic parameters, biochemical markers, histopathological, and echocardiographic assessments were evaluated. Immunohistochemistry for eNOS expression was performed. In vitro, ISO-induced cytotoxicity and calcium overload were assessed in H9C2 cells. CYP inhibition and metabolite docking studies were also conducted. RESULTS: In the L-NAME model, high-dose KGS reduced SBP and RR intervals and enhanced cardiac eNOS expression, indicating reduced cardiac workload. In the ISO model, high-dose KGS significantly attenuated QTc prolongation, SBP elevation, and biomarker levels and ameliorated myocardial histopathological damage. Echocardiography showed decreased LV mass and wall thickness, confirming reduced cardiac remodeling. In vitro, KGS showed protective effects on H9C2 cells at 200 μg/mL by reducing ISO-induced cytotoxicity and calcium overload. CYP inhibition was minimal. Metabolite profiling identified 19 tentative metabolites; tiliroside and trehalose showed strong docking affinity toward eNOS and β1-adrenergic receptors, respectively. DISCUSSION: This study demonstrated that high-dose KGS offers significant cardioprotection by attenuating LNAME- induced hypertension and ISO-induced cardiac hypertrophy through improved eNOS expression, reduced fibrosis, oxidative stress, and intracellular calcium overload. It restored cardiac structure and function, normalized key biochemical markers (Ang-II, NA, Aldosterone, ANP), and enhanced electrical conductance without notable cytotoxicity or CYP enzyme inhibition. LC -MS and docking studies identified bioactive metabolites targeting eNOS and β1 receptors, supporting a multi-target mechanism. CONCLUSION: KGS exhibits significant cardioprotective effects by reducing cardiac workload, improving myocardial structure, and attenuating hypertrophic responses. Its low CYP inhibition potential supports its use as an adjuvant therapy for hypertensive and hypertrophic cardiac conditions.
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