DARU Journal of Pharmaceutical Sciences最新文献

{"title":"Are SGLT2 inhibitors really associated with increased urinary tract infection risk? A trial-level meta-analysis across type 2 diabetes, heart failure, and chronic kidney disease.","authors":"Andrea Matteucci, Stefania Angela Di Fusco, Michela Bonanni, Lorenzo Castello, Stefano Aquilani, Silvio Fedele, Federico Nardi, Furio Colivicchi","doi":"10.1007/s40199-026-00637-7","DOIUrl":"10.1007/s40199-026-00637-7","url":null,"abstract":"<p><strong>Background: </strong>Sodium-glucose cotransporter 2 (SGLT2) inhibitors are established therapies across the cardiovascular-renal continuum. Although the excess risk of external genital infection is well recognized, the association between SGLT2 inhibition and urinary tract infection (UTI), particularly serious/complicated urinary infection, remains uncertain.</p><p><strong>Methods: </strong>We conducted a systematic review and meta-analysis of randomized placebo-controlled trials of empagliflozin, dapagliflozin, canagliflozin, ertugliflozin, and bexagliflozin in adults with type 2 diabetes, chronic kidney disease, or heart failure. Co-primary urinary safety outcomes were any UTI and serious/complicated urinary infection, the latter defined using directly reported serious UTI endpoints or the closest reported severe urinary phenotype. Sensitivity analysis, subgroup analyses by drug and population, leave-one-out analyses, and exploratory meta-regression were performed.</p><p><strong>Results: </strong>A total of 14 studies were included. For the primary any-UTI analysis, 11 studies contributed data, comprising 62,542 participants and 4,685 events. SGLT2 inhibitors were associated with a pooled RR of 1.14 (95% CI 0.99-1.32; P = 0.073), with substantial heterogeneity (I²=76.0%). In the prespecified sensitivity analysis excluding reconstructed CANVAS estimates, 10 studies comprising 52,400 participants and 4,019 events yielded a pooled RR of 1.08 (95% CI 1.00-1.18; P = 0.060), with lower heterogeneity (I²=23.3%). For the serious/complicated urinary infection analysis, 7 studies comprising 34,396 participants and 339 events were available. The pooled RR was 0.99 (95% CI 0.78-1.27; P = 0.960), with no detectable heterogeneity (I²=0.0%). No significant subgroup differences were observed by individual SGLT2 inhibitor or by clinical population.</p><p><strong>Conclusions: </strong>SGLT2 inhibitors were not associated with a statistically significant increase in any UTI or serious/complicated UTI. These findings support a distinction between lower-grade urinary events and clinically severe urinary infection, and suggest that urinary safety concerns should not be considered equivalent to the established excess risk of external genital infection.</p>","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":"34 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13451175/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148683825","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":"Exosome-mediated siRNA delivery in cancer: Loading strategies, targeting approaches, and therapeutic outcomes.","authors":"Amr Ali Mohamed Abdelgawwad El-Sehrawy, Hassan Youssef Hussein, Ozodbek Nematov, Mirza R Baig, Dhara N Patel, Priya Priyadarshini Nayak, Safa Alkayyat, Neeraj Bainsal, Gunjan Singh, Tina Saeed Basunduwah","doi":"10.1007/s40199-026-00631-z","DOIUrl":"10.1007/s40199-026-00631-z","url":null,"abstract":"<p><p>Exosome-mediated delivery of small interfering RNA (siRNA) has emerged as a promising therapeutic strategy for cancer treatment, offering precise gene silencing with minimal off-target effects. Exosomes, naturally secreted extracellular vesicles, provide biocompatible carriers that protect siRNA from enzymatic degradation and facilitate efficient uptake by tumor cells. Their natural tropism, driven by surface proteins such as integrins and tetraspanins, promotes cellular adhesion and interactions within the tumor microenvironment, facilitating the delivery of therapeutic cargo. Preclinical studies have demonstrated that exosome-delivered siRNAs can suppress oncogenes, inhibit tumor growth, reverse chemoresistance, and modulate immune responses by targeting stromal and immune components. Engineering approaches, including surface functionalization and hybrid exosome-nanoparticle systems, further enhance stability, payload capacity, and tumor-homing efficiency. Combination strategies with chemotherapy, immunotherapy, or phototherapy have shown synergistic effects, allowing simultaneous inhibition of survival pathways, promotion of apoptosis, and remodeling of the immunosuppressive microenvironment. Early-phase clinical studies indicate safety, effective biodistribution, and functional gene silencing, highlighting the translational potential of exosome-mediated siRNA therapeutics. Challenges such as scalable production, cargo heterogeneity, and regulatory considerations remain, but ongoing advances in exosome engineering and patient-derived vesicles are poised to overcome these barriers. This review aims to comprehensively summarize the current state, therapeutic applications, and translational prospects of exosome-mediated siRNA delivery in cancer.</p>","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":"34 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13433877/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148663607","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":"Isoquercitrin suppresses neuronal ferroptosis in ischemic stroke via SIRT1-mediated deacetylation of H3K9 at the RBM15 promoter.","authors":"Shichang Cai, Siqi Zhou, Yicheng Wang, Zhen Li, Hongzhu Long, Yiping Chen, Meichun Wu, Xiuping Li","doi":"10.1007/s40199-026-00629-7","DOIUrl":"10.1007/s40199-026-00629-7","url":null,"abstract":"<p><strong>Background: </strong>Isoquercitrin (ISO), a neuroprotective flavonoid, alleviates ischemic stroke (IS) by inhibiting ferroptosis. In present study, we explored the mechanism of ISO attenuates neuronal ferroptosis in IS.</p><p><strong>Methods: </strong>HT22 cells and primary neurons underwent oxygen-glucose deprivation/reoxygenation (OGD/R) to mimic in vitro IS. Dual‑luciferase reporter assays detected luciferase activity. H3K9 acetylation levels at the RBM15 promoter were assessed by ChIP. The m6A modification of SLC25A28 mRNA was analyzed by MeRIP. The binding of RBM15 and IGF2BP3 to SLC25A28 mRNA was examined via RIP. Lipid and intracellular ROS levels were measured by C11-BODIPY and DCFH-DA staining. The levels of ferroptosis-related indicators were determined with commercial kits. Cell viability was examined using the CCK-8 assay. In vivo, the middle cerebral artery occlusion (MCAO) rat model was used to explore the effect of ISO.</p><p><strong>Results: </strong>ISO protected against OGD/R-induced ferroptosis and restored viability. ISO inhibited neuronal ferroptosis by reducing RBM15 expression. ISO suppressed RBM15 via SIRT1-mediated H3K9 deacetylation. Subsequently, RBM15 promoted m6A modification of SLC25A28 mRNA to enhance its stability. Reversal of ISO-mediated ferroptosis suppression by SLC25A28 overexpression was partly counteracted by RBM15 knockdown. In the MCAO model, ISO reduced infarct volume, lowered MDA levels, and restored GPX4 expression, which were partly reversed by RBM15 overexpression.</p><p><strong>Conclusion: </strong>ISO promoted SIRT1-mediated H3K9 deacetylation at the RBM15 promoter to suppress its transcription. RBM15 downregulation inhibited SLC25A28 stability by m6A-IGF2BP3-dependent, ultimately attenuating neuronal ferroptosis in IS.</p>","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":"34 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13433688/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148663529","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":"Nanoparticles of thiolated gum ghatti for the controlled ocular delivery of Ciprofloxacin.","authors":"Muhammad Abu Sufian, Shahid Shah, Akhtar Rasul, Nabeel Ahmad, Ghulam Abbas, Muhammad Hanif, Saleha Babar, Azka Fatima, Omeira Iqbal, Maira Tahir, Nader I Namazi","doi":"10.1007/s40199-026-00632-y","DOIUrl":"10.1007/s40199-026-00632-y","url":null,"abstract":"<p><strong>Background: </strong>Conjunctivitis is the most prevalent ocular disorder and characterized by irritation, swelling and inflammation of the conjunctiva. Fluoroquinolones are the most promising classes of antibiotics and among them; ciprofloxacin (CFX) is used to treat conjunctivitis.</p><p><strong>Objectives: </strong>To provide a controlled-release approach for extended antibacterial action, CFX-loaded thiolated gum ghatti (TGG) nanoparticles were developed to overcome the drawbacks of traditional eye medications (rapid elimination, low bioavailability).</p><p><strong>Methods: </strong>Gum ghatti (GG) was thiolated with 3-mercaptopropionic acid (3-MPA) to enhance the mucoadhesion. The nanoprecipitation technique was applied to produce nanoparticles of TGG loaded with CFX. Particle size, zeta potential, FTIR, DSC, TGA, and XRD were employed to characterize GG, TGG, and nanoparticles. Permeation, mucoadhesion, ocular irritation and pharmacokinetics were performed.</p><p><strong>Results: </strong>TGG and nanoparticles contained 0.09 and 0.13 mmoL of thiol groups/mg of polymer, respectively. Nanoparticles showed a diameter of < 200 nm and PDI of < 0.3, and showed improved CFX penetration by 80% compared to pure CFX. Nanoparticulate formulation showed no ocular irritation and sustained release of CFX with improved pharmacokinetic parameters.</p><p><strong>Conclusion: </strong>Thiolation is responsible for the improved mucoadhesion of TGG (1-fold) and nanoparticle (2-fold) compared to GG, making it suitable for creating eye formulations for the treatment of bacterial infections.</p>","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":"34 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13428731/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148653034","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":"Bridging clinical toxicology and teratology: European survey of service integration.","authors":"Georgios Eleftheriou, Raffaella Butera","doi":"10.1007/s40199-026-00633-x","DOIUrl":"10.1007/s40199-026-00633-x","url":null,"abstract":"<p><strong>Background: </strong>In the last decades there has been a growing interest in pregnant and breastfeeding patient's health and growing attention to the effects of drugs and chemicals during pregnancy and lactation. For this reason, many Teratology Information Services (TIS) have been established in Europe, providing information on known reproductive risks, conducting epidemiologic research and pharmacovigilance on drug-induced congenital malformations and cooperating within the European Network of Teratology Information Services (ENTIS). The Poison Control Centres (PCC) too may be contacted by patients for the use of drugs in pregnancy and lactation, and they can provide such advise with similar or lower confidence in comparison to the TIS.</p><p><strong>Objectives: </strong>The objective of this study is to identify among the PCC members of the European Association of Poison Centres and Clinical Toxicologists (EAPCCT) those that provide information or intend to provide better information on the use of drugs during pregnancy and lactation to the patients or to health professionals, with a perspective of expanding the collaboration between these two associations by offering training through webinars or other type of scientific information.</p><p><strong>Methods: </strong>We invited the PCC in Europe to participate in a survey asking if and how they provide information about medicines during pregnancy and lactation. A second survey was carried out among the ENTIS members in order to assess the overall patients need for such type of advice.</p><p><strong>Results: </strong>Fifty-six PCC from 28 European countries received the invitation to participate in the survey. A total of 93% from 26 countries responded within 3 months after the first request. Sixty-two per cent of the PCC provide information on the use of drugs in pregnancy and lactation in the order of a 1,500-2,000 calls/year, while only 19% of the PCC include a TIS. Overall, 35% of the PCC were interested in expanding their knowledge in the teratology field. All 26 TIS from 16 countries participated in the survey: they provide information for more than 118,000 cases per year.</p><p><strong>Conclusion: </strong>The collaboration between the PCC and TIS is potentially advantageous in order to share information and to provide a training to the clinical toxicologists in the field of clinical teratology in countries where there isn't a TIS, especially in the Eastern Europe where the TIS are almost absent. This will in turn provide a benefit to the health care professionals who may lack an evidence-based knowledge on medication safety in pregnancy.</p>","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":"34 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13424008/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148618623","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":"Three-dimensional printing as a transformative platform for patient-centric pediatric drug delivery: technologies, formulation strategies and clinical translation.","authors":"Padmadip Phadte, Mythili Krishna Jeedigunta, Gopalkrishna Rao, Bothiraja Chellampillai","doi":"10.1007/s40199-026-00630-0","DOIUrl":"10.1007/s40199-026-00630-0","url":null,"abstract":"<p><strong>Background: </strong>Pediatric patients require age-appropriate dosage forms because developmental differences in physiology, pharmacokinetics and swallowing ability can significantly affect therapeutic outcomes. Conventional dosage forms are often unsuitable for children and practices such as tablet splitting, crushing or extemporaneous preparation may lead to dose inaccuracy, altered stability, poor palatability and reduced adherence. These limitations highlight the need for innovative formulation strategies that provide precise dosing while improving acceptability and therapeutic effectiveness. In this context, three-dimensional (3D) printing has emerged as a promising platform for personalized pediatric drug delivery.</p><p><strong>Objective: </strong>This review critically examines recent advances in 3D printing technologies for pediatric drug delivery and provides a formulation-focused and translational perspective by integrating pediatric therapeutic needs with technology selection, polymer considerations and dosage form design flexibility.</p><p><strong>Methods: </strong>A comprehensive literature review was conducted to evaluate recent developments in pediatric pharmaceutical applications of 3D printing. Major technologies including fused deposition modeling, semi-solid extrusion, binder jet printing and inkjet printing were assessed with respect to formulation design, polymer selection, drug-polymer compatibility and pediatric suitability. Particular emphasis was placed on taste-masking approaches, personalized dosing capability and dosage adaptability for different pediatric age groups.</p><p><strong>Results: </strong>Three-dimensional printing enables fabrication of diverse pediatric-friendly dosage forms including chewable gummies, mini-tablets, orodispersible films and confectionery-like formulations. Published studies demonstrated improved dose precision, effective taste masking, customizable drug release profiles and enhanced patient acceptability. Regulatory approval of Spritam further supports the clinical feasibility of this technology. However, challenges remain regarding printer calibration, reproducibility, limited pharmaceutical-grade printable materials, long-term stability and regulatory harmonization.</p><p><strong>Conclusion: </strong>Three-dimensional printing represents an important advancement in patient-centric pediatric pharmacotherapy by enabling precise control over dose, geometry, release kinetics and sensory attributes. This review highlights its practical potential and translational readiness for pediatric healthcare.</p>","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":"34 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13424067/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148618618","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":"Solid nano-lipoidal intelligent premix (SNIP): designing, optimization, and characterization.","authors":"Hardik Rana, Noopur Patel, Vaishali Thakkar, Tejal Gandhi","doi":"10.1007/s40199-026-00627-9","DOIUrl":"10.1007/s40199-026-00627-9","url":null,"abstract":"<p><strong>Background: </strong>Bicalutamide possesses very low oral bioavailability due to its low water solubility and p-gp efflux. The present invention aimed to improve the solubility and availability of Bicalutamide at the absorption site using Epigallocatechin-3-gallate (EGCG) and to design a patient- and industry-friendly solid nanolipoidal intelligent premix (SNIP). Exploring natural excipients is another aim.</p><p><strong>Methods: </strong>Various oils, surfactants, and cosurfactants were employed to investigate the Bicalutamide solubility. EGCG was used as a p-gp substrate to improve the absorption of Bicalutamide. An optimum proportion was defined through a pseudo-ternary phase diagram. The influence of the Soluplus as a precipitation inhibitor was assessed. Significant variables were screened using a qualitative risk assessment to design a self-nano-emulsifying drug delivery system. The influence of significant variables, such as amounts of sunflower oil, Tween 20, and Span 80, was identified using a D-optimal mixture design. SNEDDs were characterized using morphological and chemical tests. Optimal SNEDDs were adsorbed to form SNIP and characterized.</p><p><strong>Results: </strong>Sunflower oil, T20, and S80 were scrutinized as oil, surfactant, and co-surfactant based on Bicalutamide solubility. Soluplus was identified as effective at a 5% concentration as a parachute. A 1:3 proportion of Sunflower oil, Tween 20, and Span 80 was chosen from a pseudo-ternary diagram. The optimal SNEDDs have Sunflower oil (0.11mL), Tween 20 (0.14mL), and Span 80 (0.74mL), which showed immediate emulsification (13 s), nano, uniform globule size (254.4 nm and PDI < 0.5), and higher stability (-21.3 mV to -21.3 mV zeta potential). XRD, FTIR, DSC, and in-vitro dissolution revealed the amorphous nature and higher solubility of SNIP. The ex vivo method confirmed the effect of EGCG, showing higher absorption (96.75 ± 1.23%) at 2.5 min. Better thermodynamic stability was observed for optimal SNIP.</p><p><strong>Conclusion: </strong>Sunflower oil was explored as a natural oil in designing SNIP. SNIP design was significantly affected by the formulation variables. SNIP showed higher dissolution and solubility compared to pure Bicalutamide. EGCG was effective in improving the availability of Bicalutamide at the absorption site. SNIP may undergo lymphatic absorption, bypassing first-pass metabolism. The designed SNIP was novel, industrial-friendly, and patient-convenient.</p>","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":"34 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13391991/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148548146","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":"Biosynthesis, characterization, and antiproliferative activity of gold nanoparticles synthesized using Artemisia chamaemelifolia extract against cisplatin-resistant ovarian cancer cells.","authors":"Ali Shirafkan, Mohammad Sadegh Hashemzadeh, Mozafar Mohammadi","doi":"10.1007/s40199-026-00628-8","DOIUrl":"10.1007/s40199-026-00628-8","url":null,"abstract":"<p><strong>Background: </strong>Ovarian cancer remains a major clinical challenge, largely because many patients eventually develop resistance to cisplatin. In this study, gold nanoparticles (AuNPs) were synthesized using Artemisia chamaemelifolia extract through a green chemistry approach, and their antiproliferative activity was evaluated in cisplatin-resistant A2780cp ovarian cancer cells.</p><p><strong>Methods: </strong>The aqueous extract of the plant was used as both the reducing and stabilizing agent during nanoparticle formation. The synthesized AuNPs were characterized using UV-Vis spectroscopy, FTIR, FESEM, TEM, and DLS. Cytotoxic effects were assessed using the MTT assay, while apoptosis was evaluated by Annexin V/PI flow cytometry. Changes in the expression of BAX, BCL-2, TP53, and CCND1 were assessed by RT-qPCR. HEK293 cells were included as a comparator cell line for cytotoxicity.</p><p><strong>Results: </strong>UV-Vis spectroscopy showed a surface plasmon resonance peak near 530 nm, confirming nanoparticle formation. FESEM and TEM analyses revealed well-dispersed nanoparticles with predominantly spherical to slightly cubic morphology, an average size of 15.13 nm, and a relatively narrow size distribution. The MTT assay demonstrated dose-dependent cytotoxicity, with an IC₅₀ of 38.83 µg/mL(95% CI: 31.85 to 47.28) in A2780cp cells and no IC₅₀ reached within the tested concentration range for HEK293 cells (n = 3). Accordingly, the selectivity index (SI) was estimated to be > 5.15, suggesting preferential cytotoxicity toward A2780cp cells. In contrast, cisplatin showed a lower SI of 1.24. Flow cytometry indicated an increase in early apoptotic cells from 16.1 ± 1.2% to 69.2 ± 3.4% (n = 3), accompanied by a reduction in overall viability. RT-qPCR results were consistent with these findings, showing upregulation of BAX and TP53 and downregulation of BCL-2 and CCND1.</p><p><strong>Conclusion: </strong>AuNPs synthesized by this green method exhibited selective cytotoxic and pro-apoptotic activity against cisplatin-resistant ovarian cancer cells. These findings suggest their potential as a biocompatible candidate in strategies aimed at addressing chemoresistance in ovarian cancer.</p>","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":"34 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13391982/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148548110","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":"Novel 3,3'-diindolylmethane derivatives as multi-pathway modulators: targeting estrogen-dependent and independent breast cancer carcinogenesis.","authors":"Elif Ince-Erguc, Bita Entezari, Hanif Sirinzade, Sibel Suzen, Atilla Akdemir, Oguz Erdogan, Hande Gurer-Orhan","doi":"10.1007/s40199-026-00625-x","DOIUrl":"10.1007/s40199-026-00625-x","url":null,"abstract":"<p><strong>Purpose: </strong>Breast cancer remains a leading cause of cancer-related mortality among women, with prolonged exposure to endogenous estrogens recognized as a major risk factor. This study aimed to design, synthesize, and pharmacologically evaluate novel 3,3'-diindolylmethane (DIM) derivatives as multi-target modulators of estrogen-related pathways in breast cancer.</p><p><strong>Methods: </strong>A series of DIM derivatives was synthesized and structurally characterized. Their biological activities were assessed through aromatase (CYP19A1) and CYP1B1 inhibition assays, E-screen assay for estrogen receptor activity, cytotoxicity assays in breast cancer (MCF-7 BUS, MDA-MB-231) and normal breast epithelial (MCF-10 A) cells, and scratch assay for cell migration. Molecular docking and in silico ADME analyses were conducted to support experimental findings.</p><p><strong>Results: </strong>The derivatives demonstrated significant antiestrogenic activity by targeting multiple components of estrogen signaling. One compound exhibited potent aromatase inhibition (IC₅₀ = 0.79 µM), while two derivatives showed strong CYP1B1 inhibition (IC₅₀ = 0.37 µM and 0.71 µM). Selective cytotoxicity was observed in estrogen receptor-positive cells, with reduced effects on normal cells. Additionally, selected compounds significantly inhibited cell migration. Molecular modeling revealed favorable binding interactions within target enzymes, and ADME analysis indicated acceptable drug-like properties.</p><p><strong>Conclusion: </strong>These findings suggest that DIM derivatives act as selective, multi-target modulators of estrogen-related pathways and may serve as promising adjuvant candidates for hormone-dependent breast cancer therapy.</p>","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":"34 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13391475/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148548097","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":"Cost-Effectiveness of olaparib plus bevacizumab versus bevacizumab monotherapy as first-line maintenance for patients with advanced ovarian cancer: a analysis from a Chinese healthcare perspective.","authors":"Pengxiang Cai, Jin Liu, Caifen Yu, Qing Chen, Shan Huang, Lingjun Zeng, Yong Sun, Aiwen Huang","doi":"10.1007/s40199-026-00621-1","DOIUrl":"10.1007/s40199-026-00621-1","url":null,"abstract":"<p><strong>Objective: </strong>The PAOLA-1 trial demonstrated that olaparib plus bevacizumab (OB) significantly prolonged progression-free survival (PFS) and overall survival (OS) compared to bevacizumab monotherapy (BM) as first-line maintenance therapy for patients with advanced ovarian cancer (AOC) who had homologous recombination deficiency (HRD)-positive status at high risk of disease progression (HRisk-HRD⁺), including both the breast cancer susceptibility gene mutated (BRCAm) subgroup and the BRCA wild-type (BRCAwt) subgroup. This study aimed to assess its cost-effectiveness from the perspective of the Chinese healthcare system.</p><p><strong>Methods: </strong>A state-transition Markov model over a 20-year lifetime horizon was developed to evaluate the cost-effectiveness of OB compared to BM. The willingness-to-pay (WTP) thresholds were set at 1 to 3 times the gross domestic product per capita of China in 2024 ($13444.68 to $40334.05/QALY). The primary outcomes included total costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs). Subgroup analysis, sensitivity analysis and scenario analyses were performed to validate the robustness of the study.</p><p><strong>Results: </strong>Compared with BM, the ICERs of OB were $10806.70/QALY, $10478.80/QALY and $25114.44/QALY in the HRisk-HRD⁺ population, BRCAm subgroup and BRCAwt subgroup, respectively. OB demonstrated potential cost-effectiveness for patients with HRisk-HRD⁺ AOC, particularly those with a BRCA mutation. One-way sensitivity analysis indicated that the discount rate and the price of olaparib were the primary factors influencing the ICER. The results of the probabilistic sensitivity analysis and scenario analysis were generally consistent with those of the base-case analysis.</p><p><strong>Conclusions: </strong>Compared to BM, OB demonstrated superior cost-effectiveness as first-line maintenance therapy for patients with HRisk-HRD⁺ AOC, particularly those with a BRCA mutation in China.</p>","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":"34 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13391478/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148548124","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}