DARU Journal of Pharmaceutical Sciences最新文献

{"title":"Yiqi Guben capsule alleviates asthmatic airway inflammation through the miR-34a-5p/Notch1 pathway associated with Treg/Th17 immune balance.","authors":"Yinan Guo, Yibu Kong, Aiai Dong, Yue Shao, Xinyan Yu, Jinguang Zhao, Shuang Zu, Hao Yue, Anning Li, Yongji Wang, Liping Sun","doi":"10.1007/s40199-026-00662-6","DOIUrl":"10.1007/s40199-026-00662-6","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to explore the mechanisms by which YQGB regulates the balance between regulatory T cells (Tregs) and T helper 17 cells (Th17) and clarify its role in the inflammatory response associated with asthma.</p><p><strong>Methods: </strong>A total of 60 BALB/c mice were randomly divided into six experimental groups: the control group, the OVA-induced asthma model group (OVA group), the high-dose YQGB treatment group (YQGB(H) group), the medium-dose YQGB (YQGB(M) group), the low-dose YQGB (YQGB(L) group), and the dexamethasone positive control (DEX group). Serum and lung tissue samples were collected to evaluate inflammatory cytokine expression, Treg and Th17 cell proportions, an relevant molecular markers. In vitro, LPS-stimulated MH-S monocultures and MH-S/CD4⁺ T co-culture systems were constructed to mimic pulmonary inflammatory microenvironments, followed by YQGB-containing serum intervention to explore the miR-34a-5p/Notch1 regulatory axis.</p><p><strong>Results: </strong>Our results showed that YQGB decreased the expression of IL-6, IL-17 A, IL-23, GM-CSF, and Notch1 and promoted the expression of anti-inflammatory cytokines (IL-10 and IL-35) and miR-34a-5p in vivo and in vitro. In mice with OVA-induced asthma, YQGB restored the imbalance in Treg/Th17 and alleviated inflammation and EMT. In LPS-induced MH-S cells, YQGB attenuated inflammatory activation by inhibiting macrophage proliferation and enhancing apoptosis. Additionally, LPS stimulation considerably decreased miR-34a-5p expression, while increasing Notch1 expression.</p><p><strong>Conclusion: </strong>YQGB alleviates asthmatic airway inflammation, accompanied by altered Treg/Th17 immune balance. Although its therapeutic effects correlate with the miR-34a-5p/Notch1 axis, the causal cascade linking this axis to Treg/Th17 homeostasis remains unproven, indicating its potential as a candidate asthma treatment.</p>","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":"34 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13620061/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149073929","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapy resistance-related ncRNAs in cervical cancer: biomarkers and therapeutic targets.","authors":"Lili Liu, Limei Zhang, Zhe Ma","doi":"10.1007/s40199-026-00660-8","DOIUrl":"10.1007/s40199-026-00660-8","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Cervical cancer remains a major cause of cancer-related morbidity and mortality, and resistance to chemoradiotherapy, systemic chemotherapy, and emerging targeted or immune-based therapies continues to limit durable disease control. Non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), and extracellular-vesicle-associated transcripts, are increasingly recognized as regulators of DNA-damage repair, apoptosis, epithelial-mesenchymal plasticity, stemness, metabolic adaptation, ferroptosis, and tumor-microenvironmental communication in treated cervical tumors.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;This narrative review aimed to critically synthesize therapy resistance-related ncRNAs in cervical cancer using a resistance-centered and translational framework that extends beyond previous reviews focused predominantly on individual ncRNA classes, cisplatin resistance, or broader ncRNA biology. The review integrates miRNAs, lncRNAs, circRNAs, and extracellular-vesicle-associated ncRNAs across therapeutic modalities and evaluates them according to recurrent resistance mechanisms, level of experimental or patient-associated validation, biomarker readiness, and therapeutic tractability.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;A narrative literature search of PubMed, Scopus, Web of Science, and Google Scholar was conducted up to June 2026 to identify studies linking miRNAs, lncRNAs, circRNAs, and extracellular-vesicle-associated ncRNAs with treatment resistance, treatment sensitivity, or clinical response in cervical cancer. Evidence was synthesized according to treatment modality, mechanistic resistance program, biological source, level of validation, biomarker readiness, and therapeutic tractability.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;The available evidence indicates that ncRNA networks contribute to therapy resistance by regulating DNA-damage repair, survival signaling, epithelial-mesenchymal transition, cancer stem-cell phenotypes, drug efflux, metabolic adaptation, ferroptosis, and exosome-mediated intercellular communication. Conversely, several ncRNAs can restore chemosensitivity or radiosensitivity by promoting apoptosis or ferroptosis and impairing repair of therapy-induced damage. Particular attention is given to circulating and exosomal ncRNAs as investigational biomarker candidates that have shown associations with treatment response or clinical outcome, while emphasizing that prospective and independent clinical validation remains lacking. Finally, antisense oligonucleotides, small interfering RNAs, miRNA mimics, anti-miRs, nanoparticle systems, and engineered exosomes are discussed as experimental or early translational therapeutic approaches, with particular attention to unresolved challenges related to delivery, safety, target specificity, and context-dependent function.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;By moving beyond a transcript-by-transcript catalogue, this rev","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":"34 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13594077/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149015858","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Technology profiles in FDA-approved new molecular entities, 2013-2024: a latent class analysis.","authors":"Soon Kyu Jung","doi":"10.1007/s40199-026-00665-3","DOIUrl":"10.1007/s40199-026-00665-3","url":null,"abstract":"<p><strong>Background: </strong>Pharmaceutical innovation is often described using isolated approval-time attributes such as modality, first-in-class status, or expedited designations, but this approach does not reveal how multiple technological attributes are combined within the approved-drug portfolio.</p><p><strong>Methods: </strong>We analyzed 496 therapeutic new molecular entities approved by the U.S. Food and Drug Administration between 2013 and 2024 using therapeutic modality, mechanism of action, target class, and therapeutic area. Latent class analysis identified recurring technology profiles, and their prevalence was compared across four three-year approval periods using Pearson's chi-square test.</p><p><strong>Results: </strong>A retained four-class solution identified an enzyme-centered inhibitory small-molecule profile (35.3%), a receptor-centered mixed-mechanism profile (27.8%), an antibody receptor-ligand profile (22.4%), and a heterogeneous alternative-modality profile (14.5%). The inhibitory small-molecule profile was the largest in all four periods, while all four profiles were represented throughout the study period. The antibody receptor-ligand profile accounted for 15.2% of approvals in 2013-2015 and 26.1% in 2022-2024, whereas the receptor-centered mixed-mechanism profile accounted for 34.3% and 24.6%, respectively. The overall profile distribution was not significantly associated with approval period (χ² = 7.94, p = 0.541).</p><p><strong>Conclusions: </strong>FDA-approved NMEs were organized into four recurring multidimensional technology profiles. The enzyme-centered inhibitory small-molecule profile remained the largest, while antibody, receptor-centered, and alternative-modality profiles also represented substantial portfolio components. These findings demonstrate the coexistence of multiple technological patterns and show how approval-time attributes are combined in approved medicines.</p>","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":"34 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13594018/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149015818","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Personalized neoantigen mRNA vaccines for pancreatic cancer: the role of lipid nanoparticle delivery systems.","authors":"Dipayan Debnath","doi":"10.1007/s40199-026-00664-4","DOIUrl":"10.1007/s40199-026-00664-4","url":null,"abstract":"<p><strong>Background: </strong>Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy characterized by late diagnosis, frequent recurrence, limited treatment options, and an immunosuppressive tumor microenvironment. These features have encouraged the development of personalized approaches targeting tumor-specific neoantigens.</p><p><strong>Objective: </strong>This review discusses the development and therapeutic potential of personalized neoantigen mRNA vaccines for PDAC, with particular emphasis on lipid nanoparticle (LNP) delivery systems and their role in shaping antitumor immunity.</p><p><strong>Methods: </strong>Published literature on PDAC, neoantigen identification, personalized cancer vaccines, mRNA engineering, and LNP-based delivery was reviewed and synthesized, with emphasis on preclinical findings, clinical evidence, and translational challenges.</p><p><strong>Results: </strong>Advances in sequencing and computational approaches have improved the identification of patient-specific neoantigens, while mRNA platforms allow multiple neoantigens to be encoded in a flexible vaccine format. LNPs provide protection and efficient intracellular delivery of mRNA and can also influence antigen-presenting cell activation, inflammatory signaling, and T-cell responses. Preclinical studies have demonstrated neoantigen-specific immunity and improved tumor control in PDAC models. Early clinical studies of autogene cevumeran showed measurable vaccine-induced T-cell responses, with an association between stronger immune responses and longer recurrence-free survival. However, these findings remain preliminary because of small study populations and the absence of randomized controls. Tumor heterogeneity, immunosuppression, neoantigen prediction, manufacturing complexity, cost, and delivery barriers remain important challenges.</p><p><strong>Conclusion: </strong>Personalized neoantigen mRNA vaccines delivered through LNPs represent a promising investigational strategy for PDAC. Further advances in neoantigen selection, mRNA engineering, LNP optimization, targeted delivery, and clinical evaluation are needed to establish their safety, efficacy, and therapeutic role.</p>","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":"34 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13593978/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149015771","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Important potential risks not reflected in Japanese drug labeling: implications for risk management plan termination.","authors":"Natsuko Kameyama, Ayana Ide, Hideki Maeda","doi":"10.1007/s40199-026-00661-7","DOIUrl":"10.1007/s40199-026-00661-7","url":null,"abstract":"<p><strong>Background: </strong>Risk management plans (RMPs) support lifecycle management of drug-related risks. In Japan, however, their use in clinical practice remains limited, and healthcare professionals often rely on the package insert for safety information. After RMP termination at re-examination, healthcare professionals may no longer readily identify unresolved risks absent from the package insert through either the package insert or the Pharmaceuticals and Medical Devices Agency (PMDA) RMP source.</p><p><strong>Objectives: </strong>We investigated the extent to which important potential risks in RMPs are reflected in the package insert and considered the implications of RMP termination when such risks remain undocumented.</p><p><strong>Methods: </strong>We analyzed RMPs publicly available as of May 2023 using data from the PMDA website. For each important potential risk, we examined whether it was documented in the package insert and summarized the results descriptively by risk type.</p><p><strong>Results: </strong>Among 772 important potential risks in 330 RMPs, 134 (17.4%) were not documented in the package insert. Non-documentation proportions were relatively high for \"Infections and infestations\" (32.7%), \"Gastrointestinal disorders\" (32.4%), and \"Neoplasms benign, malignant and unspecified (incl cysts and polyps)\" (28.4%), whereas a relatively low proportion was observed for \"Vascular disorders\" (2.3%).</p><p><strong>Conclusion: </strong>Some important potential risks in active Japanese RMPs were not documented in the package insert. This may create gaps in risk communication after RMP termination, although clinical outcomes and patient harm were not assessed. Allowing RMP continuation beyond re-examination when necessary may help maintain awareness of unresolved safety concerns.</p>","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":"34 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13586118/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148987867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prasugrel in the management of acute coronary syndromes: a systematic review.","authors":"Canan Akman, Asli Bahar Ucar, Mehmet Unaldi, Gul Kilic, Busra Erdem, Pinar Vargun, Sennaz Sahin, Bilgen Ozkaya, Ozgur Karcioglu","doi":"10.1007/s40199-026-00636-8","DOIUrl":"10.1007/s40199-026-00636-8","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background and objective: &lt;/strong&gt;Prasugrel is a third-generation thienopyridine P2Y12 receptor inhibitor with superior pharmacological properties compared with clopidogrel, offering faster onset, greater potency, and more predictable platelet inhibition. This review critically evaluates the evidence base underpinning the rational use of prasugrel in acute coronary syndromes (ACS), encompassing its pharmacology, comparative efficacy across clinical subtypes, safety profile, special population considerations, and place in contemporary clinical practice.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;A systematic search was employed to abstract studies related to the rational use of prasugrel in ACS from the literature. All English studies from 2010 to 2026 focusing on the effectiveness and safety profile of the agent were abstracted after a search in Google Scholar, PubMed, Scopus, Web of Science, and MEDLINE. The PubMed/MEDLINE component of the search was executed on 17 July 2026 using the strategy (\"prasugrel\"[All Fields] OR \"prasugrel hydrochloride\"[MeSH Terms]) AND (\"coronary\"[All Fields] OR \"heart\"[MeSH Terms]) AND (\"syndrome\"[MeSH Terms]) AND (\"infarction\"[MeSH Terms]); this returned 779 records, which were reduced to 607 after limiting to English-language human studies published between 2010 and 2026, and to 202 reports meeting the prioritised study-design criteria (randomised controlled trials, meta-analyses, systematic reviews, and clinical practice guidelines) that were assessed in full text. The numbers of records identified, screened, assessed for eligibility, and included are summarised in the PRISMA 2020 flow diagram (Fig. 1), and the full electronic search string with translated field tags is provided as Supplementary Material (Table S1). Case reports, editorials, corrigenda, unpublished data, letters, and opinion articles were excluded from the analysis. Selected high-quality observational studies and post-marketing registries were, however, additionally incorporated to inform real-world effectiveness and special-population questions for which randomised data are limited or under-powered. Evidence was collated narratively and presented in tabular format. The quality of evidence for the trials was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. The review was conducted and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 statement.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Prasugrel offers clinically meaningful reductions in ischaemic events compared with clopidogrel in ACS patients undergoing percutaneous coronary intervention and demonstrated superiority over ticagrelor in major trials. Careful patient selection is mandatory, with absolute contraindications including prior stroke or transient ischaemic attack and active pathological bleeding.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;In eligible ACS patients proceeding to intervent","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":"34 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13586102/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148988269","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acetaminophen-induced acute liver injury abrogates the cytosine methylation pathway.","authors":"Dilkash Ara, Bathula Ziona, Sathish Kumar Mungamuri","doi":"10.1007/s40199-026-00659-1","DOIUrl":"10.1007/s40199-026-00659-1","url":null,"abstract":"<p><strong>Purpose: </strong>Acetaminophen overdose is a leading cause of drug-induced liver injury (DILI) and acute liver failure. Traditional markers such as AST, ALT, and ALP detect damage only after significant hepatocellular injury. This study aimed to identify early epigenetic events, focusing on microRNA (miRNA) regulation of ten-eleven translocation (TET) enzymes, and to evaluate their potential as biomarkers for early detection of DILI.</p><p><strong>Methods: </strong>Next-generation miRNA sequencing was performed in HepG2 cells exposed to acetaminophen. Bioinformatic analysis identified target pathways and predicted miRNA-TET interactions. Validation was conducted in vitro (HepG2 cells) and in vivo (C57BL/6J male mice) using gene expression assays and 5 methyl cytosine profiling.</p><p><strong>Results: </strong>Forty-four miRNAs were significantly upregulated following acetaminophen treatment. These miRNAs were enriched in pathways including Akt, fatty acid metabolism, ERK, and mTOR signaling. A subset directly targeted TET1 and TET2, resulting in their downregulation in both HepG2 cells and mouse liver tissue. This suppression correlated with increased global 5-methylcytosine (5mC) levels, indicating enhanced DNA methylation. Importantly, these epigenetic changes occurred at early stages of acetaminophen exposure, preceding overt necrosis.</p><p><strong>Conclusion: </strong>This study demonstrates that miRNA-mediated downregulation of TET enzymes and the resulting accumulation of 5mC represent early molecular events in acetaminophen-induced liver injury. These findings highlight the potential of miRNAs and DNA methylation changes as early biomarkers of DILI and suggest novel therapeutic targets for mitigating acetaminophen hepatotoxicity.</p>","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":"34 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13586097/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148987875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Artificial intelligence-driven digital twins in Pharma 4.0: transforming smart manufacturing, predictive quality assurance, and personalized drug delivery.","authors":"Chetana Krushna Belkare, Omkar Vishnu Daware","doi":"10.1007/s40199-026-00655-5","DOIUrl":"10.1007/s40199-026-00655-5","url":null,"abstract":"<p><strong>Purpose: </strong>The rapid advancement of Pharma 4.0 has accelerated the integration of artificial intelligence (AI), digital twins, and data-driven technologies into pharmaceutical research, manufacturing, and healthcare. This review aims to critically evaluate the role of AI-driven digital twins across the pharmaceutical lifecycle, with emphasis on smart manufacturing, predictive quality assurance, continuous manufacturing, regulatory validation, personalized drug delivery, and precision medicine. The review addresses how AI-enabled digital twins can overcome limitations of conventional pharmaceutical systems and support predictive, adaptive, and patient-centric approaches.</p><p><strong>Methods: </strong>A comprehensive literature-based review was conducted by analyzing recent scientific publications, regulatory perspectives, and technological developments related to digital twins, AI, Process Analytical Technology (PAT), Quality by Design (QbD), Pharma 4.0, and emerging Pharma 5.0 concepts. Relevant evidence from pharmaceutical manufacturing, bioprocessing, healthcare applications, and supporting industrial domains was critically evaluated.</p><p><strong>Results: </strong>AI-driven digital twins enable real-time process monitoring, prediction of critical quality attributes, optimization of manufacturing operations, predictive maintenance, and support for real-time release testing. Integration with advanced technologies, including nanotechnology, biosensors, wearable devices, and computational modeling, provides new opportunities for personalized drug delivery and precision medicine. However, challenges associated with data integrity, model validation, interoperability, cybersecurity, regulatory acceptance, and limited pharmaceutical datasets remain significant barriers.</p><p><strong>Conclusion: </strong>AI-driven digital twins represent a transformative approach for developing intelligent pharmaceutical ecosystems. Their successful implementation requires robust validation frameworks, regulatory guidance, interdisciplinary collaboration, and continued advancement toward reliable, sustainable, and patient-centered pharmaceutical systems.</p>","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":"34 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13582718/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148982009","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of nanoemulsion-based in situ gel formulation of escitalopram oxalate for intranasal delivery in depression therapy.","authors":"Vahid Vikram Minglani, Meenakshi B Patel, Tarun Kumar Upadhyay","doi":"10.1007/s40199-026-00635-9","DOIUrl":"10.1007/s40199-026-00635-9","url":null,"abstract":"<p><strong>Background: </strong>Escitalopram oxalate is a Biopharmaceutics Classification System (BCS) Class II drug with low aqueous solubility and significant first-pass metabolism, limiting its systemic bioavailability and therapeutic efficiency. Intranasal delivery using a nanoemulsion-based thermosensitive in situ gelling system offers a promising strategy to bypass first-pass metabolism, improve drug solubility, prolong nasal residence time, and facilitate nose-to-brain drug delivery.</p><p><strong>Objective: </strong>This study aimed to develop and optimize a nanoemulsion-based in situ gel for the intranasal delivery of escitalopram oxalate to improve drug delivery and antidepressant efficacy.</p><p><strong>Methods: </strong>Escitalopram-loaded nanoemulsions were prepared by high-energy emulsification using a hybrid oil phase of arachis oil and Caproyl 90 (1:1), Tween 80 as the surfactant, and PEG 400 as the cosurfactant. Formulations were optimized using a Central Composite Design (CCD) and characterized for droplet size, polydispersity index (PDI), zeta potential, drug content, gelation temperature, pH, viscosity, spray characteristics, in vitro drug release, ex vivo nasal permeation, nasal ciliotoxicity, RPMI 2650 cell viability, and pharmacodynamic activity in Wistar rats.</p><p><strong>Results: </strong>The optimized formulation exhibited a droplet size of 34.93 nm, PDI of 0.1955, zeta potential of - 38.4 mV, 97% drug content, pH of 6.4 ± 0.93, and a gelation temperature of 34 ± 1 °C. The formulation demonstrated sustained drug release over 8 h, significantly enhanced ex vivo nasal permeation compared with the nanoemulsion alone, uniform spray performance, and an acceptable safety profile in nasal ciliotoxicity and RPMI 2650 cell viability studies. Pharmacodynamic evaluation showed significantly greater reduction in depressive-like behaviours than oral escitalopram solution.</p><p><strong>Conclusion: </strong>The optimized nanoemulsion-based in situ gel demonstrated sustained drug release, enhanced nasal permeation, acceptable safety, and improved antidepressant efficacy. These findings indicate that the developed formulation is a promising non-invasive platform for intranasal delivery of escitalopram oxalate with the potential to enhance nose-to-brain delivery for depression therapy.</p>","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":"34 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13582788/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148981924","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Terpenoids as modulators of autophagy-senescence crosstalk in lung cancer.","authors":"Kambati Niharika, Nagakanni Muthuvenugopal, Mamali Das, Chandramohan Kiruthiga","doi":"10.1007/s40199-026-00634-w","DOIUrl":"10.1007/s40199-026-00634-w","url":null,"abstract":"<p><p>Lung cancer (LC) is ranked among the top causes of cancer death in the world, with little success achieved by currently available therapies due to late diagnoses, resistance, and side effects. Terpenoids, which are secondary metabolites produced by plants, have been extensively investigated for their anticancer activities. Preclinical studies demonstrate that terpenoids affect important cellular mechanisms like autophagy and cellular senescence (CS), which have both tumor-suppressive and tumor-progressive effects. The present study summarizes the effects of 46 structurally diverse terpenoids including monoterpenoids, diterpenoids, triterpenoids, sesquiterpenoids, and their analogs on autophagy and CS in pulmonary cancer cells. Interestingly, most of these agents were reported to affect both pathways by targeting central nodes of signaling pathway, which include AMP-activated protein kinase (AMPK), Nuclear factor-kappa B (NF-κB), mitogen-activated protein kinase (MAPK)/Extracellular signal-regulated kinase (ERK)/c-Jun N-terminal kinase (JNK), phosphoinositide 3-kinase (PI3K)/alpha serine/threonine kinase (AKT)/ mechanistic target of rapamycin (mTOR), reactive oxygen species (ROS) and tumor protein (p53), retinoblastoma proteins (Rb), Cell Cycle Arrest, and Senescence-associated secretory phenotype (SASP) factors. The review highlighted that autophagy and CS can be exploited in lung cancer treatment to provide an improved benefit to patients. Although preclinical studies provide promising evidence for the anticancer potential of terpenoids, their clinical translation is limited by poor solubility, low bioavailability, and challenges in targeted delivery.</p>","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":"34 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13569772/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148944173","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}