DARU Journal of Pharmaceutical Sciences最新文献

{"title":"Quercetin-loaded invasomal gel: preparation, optimization, in vitro evaluation and ex vivo skin permeation evaluation.","authors":"Janavi Sosa, Prachi Pimple","doi":"10.1007/s40199-026-00652-8","DOIUrl":"10.1007/s40199-026-00652-8","url":null,"abstract":"<p><strong>Background: </strong>Skin cancer is one of the most common cancers, and effective topical delivery of therapeutic agents is limited by the skin barrier. Quercetin (QUR), a natural flavonoid with antioxidant and antiproliferative properties, has limited application due to its poor solubility and low skin permeability.</p><p><strong>Objective: </strong>The study aimed to develop and optimize QUR-loaded invasomes (QUR-INV) for topical administration.</p><p><strong>Methods: </strong>QUR-INV were prepared using the thin-film hydration method and optimized using a full factorial design, where characterization involve vesicles size, zeta potential, and entrapment efficiency (EE%). Evaluations included in-vitro release, ex-vivo skin permeation, dermatokinetics analysis, antioxidant activity, and cytotoxicity study.</p><p><strong>Results: </strong>The optimized QUR-INV exhibited a vesicle size of 211.5 nm, low polydispersity index (PDI) of 0.219, high negative zeta potential of -37.1 mV, and entrapment efficiency of 89.5%. In-vitro release showed an initial burst release within 4 hr followed by sustained controlled release over 24hr. Ex-vivo skin permeation studies demonstrated ≈2-fold higher QUR permeation from QUR-INV gel than QUR-conventional gel; while dermatokinetic analysis confirming enhanced penetration to deeper skin layers. Antioxidant activity demonstrated that encapsulation of quercetin into invasomes preserves its intrinsic antioxidant functionality; cytotoxicity against A431 epidermoid carcinoma cells revealed significantly lower IC₅₀ for QUR-INV gel (27.96 µg/mL) versus QUR-conventional gel (52.02 µg/mL) and pure QUR (297.36 µg/mL).</p><p><strong>Conclusion: </strong>The study successfully developed and optimized the quercetin-loaded invasomal gel with desirable physicochemical characteristics and controlled drug release behaviour. The formulation demonstrated enhanced cytotoxic activity and improved skin permeation, indicating its potential topical delivery system.</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/PMC13569776/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148944166","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":"From triggers to interfaces: polymer-stabilized nano-co-crystals for robust mesalazine delivery in UC.","authors":"Arif Khan, Sandeep Kumar, Anil Rajnath Singh, Mohit Agarwal, Arun Kailasiya, Junaid Qureshi","doi":"10.1007/s40199-026-00648-4","DOIUrl":"10.1007/s40199-026-00648-4","url":null,"abstract":"<p><strong>Background: </strong>Ulcerative colitis profoundly alters the colonic environment, challenging conventional oral drug delivery. Fluctuating luminal pH, irregular transit, mucus remodelling, oxidative stress and microbiota dysbiosis can destabilise trigger-dependent mesalazine formulations and contribute to inconsistent colonic drug exposure.</p><p><strong>Objective: </strong>This review examines the mechanistic limitations of trigger-dependent mesalazine delivery and evaluates whether increasing formulation complexity through multi-responsive systems provides sufficient benefit under the heterogeneous and unstable conditions of active ulcerative colitis.</p><p><strong>Methods: </strong>The review analyses how pathological changes in the colonic environment influence pH-, enzyme- and inflammation-responsive systems and considers polymer-stabilised nano-co-crystal interfacial engineering as a trigger-independent approach. Particular attention is given to crystal engineering and polymer-mediated regulation at the solid-liquid and drug-mucus interfaces.</p><p><strong>Results: </strong>Trigger-dependent systems rely on pathological cues that vary spatially and temporally during active disease, which can produce variable drug release and colonic exposure. Polymer stabilisation of nano-co-crystals provides an alternative means of controlling drug performance at the formulation interface. Polymer adsorption onto high-energy nano-co-crystal surfaces can stabilise crystalline domains, moderate dissolution, suppress aggregation and recrystallisation, and maintain controlled supersaturation under changing colonic conditions. Polymer functionality may also improve interaction with inflammation-modified mucus, prolong mucosal residence and reduce luminal washout.</p><p><strong>Conclusion: </strong>Using mesalazine as a representative drug, this review reframes colonic delivery in ulcerative colitis as an interface-dominated problem. Polymer-stabilised nano-co-crystals offer a trigger-independent strategy in which drug performance is regulated through crystal and polymer interfaces rather than fluctuating luminal conditions, providing a rational basis for further development of disease-adaptive colonic delivery systems.</p>","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":"34 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13562486/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148929071","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":"Bifidobacterium adolescentis attenuates brown adipose tissue whitening and improves metabolic markers in high-fat diet-induced obese rats.","authors":"Mahtab Mehboodi, Atefeh Khodayar, Narges Namavar, Toktam Ziaee Ghochan Atigh, Taha Zeynali, Fatemeh Hossein Mardi, Ali Alnaqeeb, Zahra Bagheri, Mahdi Alinejad, Mojtaba Hamidi Fard, Sanaz Dastghaib, Mohammad Hasan Maleki","doi":"10.1007/s40199-026-00642-w","DOIUrl":"10.1007/s40199-026-00642-w","url":null,"abstract":"<p><strong>Purpose: </strong>Activation of brown adipose tissue (BAT) has emerged as a promising strategy for combating obesity due to its thermogenic capacity. However, chronic high-fat diet (HFD) exposure impairs BAT function and promotes a \"whitening\" phenotype characterized by lipid droplet enlargement and reduced thermogenic activity. Bifidobacterium adolescentis (B. adolescentis) has been reported to improve lipid metabolism and energy balance. This study investigated whether B. adolescentis supplementation attenuates HFD-induced BAT whitening, evaluated at transcriptional and histological levels, and examined its association with thermogenic and lipolytic gene expression.</p><p><strong>Methods: </strong>Twenty-four six-weeks-old male Sprague-Dawley rats were allocated into four groups for 16 weeks: control (standard chow diet), HFD, HFD-B. adolescentis-8 W (4 × 10¹⁰ CFU/day from week 8 to week 16), and HFD-B. adolescentis-16 W (4 × 10¹⁰ CFU/day for 16 weeks). Probiotic supplementation was administered via drinking water. Metabolic parameters, serum lipid profile, BAT histomorphmetery assessed by hematoxylin and eosin staining, and mRNA expression of thermogenesis- and lipolysis-related genes (Ucp1, Prdm16, Pgc-1α, Sirt1, Ampk, Atgl, and Hsl) were evaluated.</p><p><strong>Results: </strong>B. adolescentis supplementation significantly attenuated HFD-induced weight gain and improved serum lipid parameters. These effects were accompanied by increased mRNA expression of Sirt1, Ampk, and key thermogenic and lipolytic genes in BAT. Histological analysis revealed partial preservation of multilocular adipocyte morphology and reduced cytoplasmic hypertrophy compared with the HFD group.</p><p><strong>Conclusion: </strong>B. adolescentis supplementation mitigated HFD-induced metabolic disturbances and attenuated BAT whitening. These effects were associated with the upregulation of thermogenesis- and lipolysis-related genes, including Sirt1 and Ampk. Further mechanistic studies are required to determine whether these molecular changes play a causal role in mediating the protective effects of this probiotic.</p>","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":"34 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13547202/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148900191","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":"Early-life GABA-A receptor blockade with bicuculline attenuates anxiety-like behaviors and cognitive deficits induced by 24-hr sleep deprivation in adult male rats.","authors":"Maryam Roushani, Fatemeh Aghaei, Zahra Mashhadi, Mohammad Amani, Hakimeh Saadati","doi":"10.1007/s40199-026-00658-2","DOIUrl":"10.1007/s40199-026-00658-2","url":null,"abstract":"<p><strong>Background: </strong>Early postnatal GABAergic signaling is crucial for brain development and circuit formation. While Gamma-aminobutyric acid (GABA) regulates sleep-wake cycles, sleep deprivation causes cognitive impairment and oxidative stress. Although blocking GABA-A receptors has been shown to improve cognition, the effect of such blockade during development on sleep-loss-induced cognitive deficits remains unknown.</p><p><strong>Objectives: </strong>Accordingly, this study was designed to investigate the effects of early-life inhibition of GABA-A receptors on sleep deprivation-induced cognitive impairments in adulthood.</p><p><strong>Methods: </strong>Thirty-two male neonatal rats were randomly assigned to four equal-sized groups (n = 8/group): Control, Bicuculline (300 µg/kg subcutaneously on postnatal days 7, 9, and 11), Sleep Deprivation (24-h SD at postnatal days (PNDs) 60-70), and Bicuculline + SD. In young adulthood (PNDs 60-70), anxiety-like behavior was assessed using the Elevated plus maze (EPM), while the Morris water maze (MWM) was used to evaluate spatial learning and memory. We then measured superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities, as well as malondialdehyde (MDA) levels in hippocampal tissue.</p><p><strong>Results: </strong>SD alone significantly increased anxiety-like behaviors, impaired spatial learning and short-term memory, reduced hippocampal SOD and GPx activities, and elevated MDA. Remarkably, early-life bicuculline pretreatment prevented SD-induced cognitive deficits, attenuated anxiety-like responses, and restored antioxidant enzyme activities while normalizing MDA levels.</p><p><strong>Conclusion: </strong>Early postnatal transient blockade of GABA-A receptors was associated with decreased vulnerability to cognitive deficits, anxiety-like behaviors, and oxidative stress induced by acute sleep deprivation in adulthood. This reveals a novel developmental role of early GABAergic signaling in defense against sleep loss-induced neuropsychiatric and cognitive deficits.</p>","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":"34 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13550353/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148905240","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":"TPGS-stabilized pyrimethamine micelles promote ROS-associated apoptosis in MDA-MB-231 cells and suppress tumour progression in a murine lymphoma model.","authors":"Indrajeet Yadav, Manisha Nidhar, Pavan Goud, Surya Nath Pandey, Amit Patel, Ashish Kumar Tewari, Priyanka Sonker","doi":"10.1007/s40199-026-00656-4","DOIUrl":"10.1007/s40199-026-00656-4","url":null,"abstract":"<p><strong>Background: </strong>A dihydrofolate reductase inhibitor, pyrimethamine has an emerging anticancer potential but is not well soluble in aqueous and bioavailable. The D-a-tocopheryl polyethylene glycol 1000 succinate (TPGS)-based micellar nanoformulation was developed to overcome these challenges to improve its therapeutic performance.</p><p><strong>Objective: </strong>The D-a-tocopheryl polyethylene glycol 1000 succinate (TPGS)-based micellar nanoformulation was developed to overcome these challenges to improve its therapeutic performance.</p><p><strong>Methods: </strong>TPGS micelles containing pyrimethamine were developed through solvent casting-rehydration and studied through DLS, AFM, SEM and TEM.</p><p><strong>Results: </strong>The maximally efficient expression generated homogeneous spherical micelles with an average diameter of about 74 nm and a low polydispersity (0.20) that is very homogeneous and stable. Persistent bi-phasic drug delivery was seen in physiological conditions. TPGS-Stabilized Pyrimethamine Micelles Promote ROS-Associated Apoptosis. In MDA-MB-231 breast cancer cells, the nanoformulation increased cytotoxicity and intracellular uptake compared with free pyrimethamine. The experiment showed that in mechanistic studies, there was high production of reactive oxygen species, high Annexin V-positive populations of apoptotic cells and G2/M phase arrest, which were associated with increased ROS generation, apoptosis, and cell-cycle arrest. In the murine lymphoma model, the nanoformulation reduced tumour progression and resulted in 100% survival through Day 30.</p><p><strong>Conclusion: </strong>These findings support further preclinical investigation of TPGS-based pyrimethamine micelles as a potential anticancer delivery strategy. Additional studies are required to confirm their mechanism, pharmacokinetic behaviour, long-term safety, and efficacy in breast-cancer-specific animal models.</p>","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":"34 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13546182/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148896733","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":"Ginsenoside Rb1 protects hair cell-like HEI-OC1 cells against apoptosis by inhibiting the activation of the Fas system induced by the RhoA/ROCK/LIMK1 pathway.","authors":"Wei Chang, Jiang Huang, Qiong Liao, Xinzhu Yang, Ji Bin, Wenke Wu","doi":"10.1007/s40199-026-00654-6","DOIUrl":"10.1007/s40199-026-00654-6","url":null,"abstract":"<p><strong>Background: </strong>Sensorineural hearing loss (SNHL) is a prevalent clinical disorder in otorhinolaryngology, with cochlear ischemia/reperfusion (I/R) injury-induced hair cell apoptosis being a core pathogenic mechanism. Ginsenoside Rb1 (Rb1), a major active component of Panax ginseng, exhibits potent anti-apoptotic and neuroprotective effects, but its role and underlying mechanism in cochlear I/R injury remain elusive.</p><p><strong>Methods: </strong>The hair cell-like HEI-OC1 cell line was employed to establish an in vitro cochlear I/R injury model via oxygen-glucose deprivation/reperfusion (OGD/R). Cell viability was evaluated using the CCK-8 assay to screen for the non-cytotoxic concentration of Rb1. LIMK1 knockdown was achieved by transfection with si-LIMK1, and the knockdown efficiency was verified by RT-qPCR and Western blot. Flow cytometry with Annexin V-FITC/PI staining was used to detect cell apoptosis. Western blot was performed to measure the protein expression levels of key molecules in the RhoA/ROCK/LIMK1 pathway and Fas system. The Rho/ROCK pathway inhibitor Y-27,632, the RhoA activator LPA, and Fas agonist antibody Jo2 were used to validate the regulatory relationships among the pathways.</p><p><strong>Results: </strong>OGD/R significantly induced HEI-OC1 cell apoptosis, accompanied by activation of the RhoA/ROCK/LIMK1 pathway and Fas system. Rb1 pretreatment attenuated the OGD/R-induced reduction in cell viability and increase in apoptosis, while inhibiting the activation of the RhoA/ROCK/LIMK1 pathway and Fas system. LIMK1 knockdown attenuated OGD/R-induced Fas system activation and cell apoptosis. Notably, LPA attenuated the protective effects of Rb1 and restored RhoA/ROCK/LIMK1-related protein expression, whereas Jo2 attenuated Rb1-mediated protection without affecting the upstream pathway.</p><p><strong>Conclusions: </strong>Ginsenoside Rb1 protects HEI-OC1 cells against OGD/R-induced apoptosis, and this protective effect is associated with reduced activation of the RhoA/ROCK/LIMK1 pathway and Fas system.</p>","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":"34 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13546179/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148896647","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":"Characterization of acquired capecitabine resistance in MKN-45 gastric cancer cells reveals preserved apoptotic sensitivity.","authors":"Habibeh Sadat Mohseni, Shohreh Tavajohi, Abbas Kebriaeezadeh, Mohammad Hossein Ghahremani, Seyed Nasser Ostad","doi":"10.1007/s40199-026-00653-7","DOIUrl":"10.1007/s40199-026-00653-7","url":null,"abstract":"<p><strong>Background: </strong>Capecitabine (Cap) is widely used in the treatment of advanced gastric cancer; however, the emergence of acquired resistance remains a major obstacle to its long-term efficacy. Although several gastric cancer models resistant to 5-fluorouracil (5-FU) have been reported, experimentally characterized gastric cancer models of Cap resistance remain limited.</p><p><strong>Objectives: </strong>This study aimed to establish and characterize a Cap-resistant MKN-45 gastric cancer cell model. with a focus on phenotypic alterations associated with acquired drug adaptation.</p><p><strong>Methods: </strong>A Cap-resistant MKN-45 subline (MKN-45/R-CapIC₆₀) was generated through exposure of parental MKN-45 cells to gradually increasing concentrations of Cap. Cell viability was evaluated using the MTT assay. Morphological alterations were examined by phase-contrast microscopy, while apoptosis, cell-cycle distribution, and surface c-Met expression were analyzed by flow cytometry.</p><p><strong>Results: </strong>The established resistant subline exhibited a moderate level of Cap resistance, with an approximately 2- to 4-fold increase in the resistance index (RI) compared with the parental cells. Resistant cells showed morphological remodeling characterized by an elongated spindle-like morphology and increased adherence to the culture surface compared with parental cells. Surface c-Met expression was altered in resistant cells and further decreased following Cap exposure. Despite the acquisition of a resistance phenotype, Cap exposure retained biological activity in resistant cells by reducing proliferation, altering cell-cycle distribution through impaired G1/S transition, and increasing late apoptotic/necrotic populations.</p><p><strong>Conclusions: </strong>The findings suggest that the established Cap-resistant gastric cancer cell model retains responsiveness to Cap exposure despite the acquisition of a resistance phenotype. This model may provide a useful platform for investigating early phenotypic adaptations associated with the development of drug resistance in gastric cancer.</p>","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":"34 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13542033/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148886352","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":"Patient knowledge and medication safety in chronic warfarin therapy: the roles of adherence, diet, and drug-drug interactions.","authors":"Ahmet Çakır, Melisa Sultan Tekşahin, Hasan Memiş, Mehmet Cansel","doi":"10.1007/s40199-026-00649-3","DOIUrl":"10.1007/s40199-026-00649-3","url":null,"abstract":"<p><strong>Background: </strong>Anticoagulant knowledge, medication adherence, time in therapeutic range (TTR), and potential drug-drug interactions (pDDIs) are poorly understood, but they can increase the risk of thromboembolic events, major bleeding, and mortality.</p><p><strong>Objectives: </strong>This study examined the relationship between oral anticoagulation knowledge and adherence in adults on long-term warfarin therapy, and their associations with TTR, clinical and demographic factors, bleeding risk, and pDDIs.</p><p><strong>Methods: </strong>This cross-sectional study included adults on chronic warfarin therapy at a university-affiliated cardiology clinic. Turkish versions of the validated Oral Anticoagulation Knowledge (OAK) and Anticoagulant Therapy Adherence Scale (ATAS) assessed oral anticoagulation knowledge and adherence. Clinical, laboratory, and treatment data were obtained from health records, and lifestyle information via patient interviews. pDDIs were evaluated using UpToDate^® and Micromedex^®. TTR was calculated using the Roosendaal method, and bleeding risk was assessed using the ATRIA score.</p><p><strong>Results: </strong>The study included 126 adults on warfarin therapy, with a median TTR of 31.9% and 76% of patients below 60%. Patients exhibited moderate oral anticoagulant knowledge and relatively high self-reported adherence scores. A weak positive correlation (ρ = 0.24, p = 0.006) was detected between OAK and ATAS scores, while a negative correlation (ρ=-0.179, p = 0.045) was found between OAK and concurrent medications excluding warfarin. Education and employment status were associated with OAK scores, while the frequency of vitamin K-rich food consumption was associated with ATAS scores. Age and renal impairment were associated with an increased number of concurrent medications excluding warfarin and pDDIs identified by both UpToDate^® and Micromedex^® (p < 0.05). ATAS subscale-1 scores differed significantly by education level (p = 0.033), with the highest median observed in illiterate patients and lower scores in university graduates. Higher frequency of vitamin K-rich food consumption was significantly associated with lower ATAS subscale-2 scores (p < 0.001), indicating poorer dietary adherence.</p><p><strong>Conclusion: </strong>Anticoagulation knowledge was weakly associated with adherence to warfarin therapy but not with anticoagulation control. Dietary behaviours, polypharmacy, and pDDIs may influence anticoagulation outcomes, highlighting the need for multifaceted management strategies.</p>","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":"34 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13530084/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148863811","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":"Trehalose's untapped mechanisms in alzheimer's: gut-brain-autophagy signalling beyond the usual targets.","authors":"Sathish Kumar Gunasekaran, Harshith Kariappa C K, Mirunalini Gobinath, Parikshit Roychowdhury, Manjula S N","doi":"10.1007/s40199-026-00647-5","DOIUrl":"10.1007/s40199-026-00647-5","url":null,"abstract":"<p><strong>Background: </strong>Trehalose is a promising therapeutic candidate for Alzheimer's disease (AD) that is known to induce autophagy and facilitate misfolded proteins clearance such as amyloid-β and hyperphosphorylated tau. Despite there is emerging evidence that trehalose has a wider range of molecular mechanisms and thus has a greater neuroprotective profile.</p><p><strong>Objective: </strong>To summarize the emerging molecular mechanisms underlying the neuroprotective effects of trehalose beyond classical autophagy and discuss its therapeutic potential in AD.</p><p><strong>Methods: </strong>Published evidence from preclinical studies including in-vitro and in-vivo models, along with hypothetical and emerging findings from early clinical investigations was reviewed to evaluate the molecular mechanisms, therapeutic effects, and translational challenges associated with trehalose in AD.</p><p><strong>Results: </strong>In addition to classical autophagy signalling, recent studies have demonstrated that autophagy can also regulate the stability of neuronal membrane microdomains, prevent lipid bilayers disruption by amyloid proteins, and regulate stress granules dynamics that affect the function of RNA-binding proteins. Other discoveries indicate that interactions with nutrient-sensing pathways and glucose transporter systems that simulate metabolic stress, which may activate protective mechanisms separate from the inhibition of mTOR. Trehalose could also involve in lysosomal-autophagosome fusion and modulate the microglia and astrocytes activation, suggesting an important immunometabolic function. Trehalose often connects to the gut-brain axis and show their effect in gut microbiota composition, microbial metabolite signalling and gut barrier function. These effects can influence systemic inflammation, availability of short-chain fatty acids, bile acid profiles and vagus-mediated gut-to-brain communication, all of which can influence neuroinflammation networks in AD.</p><p><strong>Conclusion: </strong>Although promising results have been reported, primarily from preclinical studies, with early human investigations now beginning to emerge, opportunities remain to address, such as poor oral bioavailability, penetration into the brain and long-term safety in elderly patients. Mechanistic dissection in multi-omics approaches, microbiome-stratified models and early-phase clinical testing are the areas that need to be targeted in future research. A broader understanding of the mechanisms of action of trehalose provides a good chance to reimagine its therapeutic implications and develop novel approaches to AD.</p>","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":"34 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13530105/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148863809","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":"Antifungal activities and toxicity studies of water-soluble non-steroidal analgesic salts.","authors":"Julian Gonzalo Arrieta, Natali Ivana Carrizo, Franco Augusto Aguilar, Guillermo Antonio Garcia Pitalluga, Diego Alejandro Sampietro, Melina Araceli Sgariglia, José Rodolfo Soberón","doi":"10.1007/s40199-026-00645-7","DOIUrl":"10.1007/s40199-026-00645-7","url":null,"abstract":"<p><strong>Background: </strong>The emergence of antifungal resistance among Candida albicans strains poses a growing clinical challenge, underscoring the urgent need for alternative therapeutic strategies. Drug repositioning of non-steroidal anti-inflammatory drugs (NSAIDs) has attracted attention due to their reported antimicrobial properties and well-established safety profiles.</p><p><strong>Objectives: </strong>This study aimed to synthesize and characterize water-soluble sodium salts of ibuprofen (IBU-Na), ketoprofen (KET-Na), and indomethacin (IM-Na), and to evaluate their antifungal activity and toxicity profiles, individually and in combination with fluconazole (FLU), against C. albicans strains.</p><p><strong>Methods: </strong>NSAID sodium salts were synthesized and characterized, and their antifungal activity, synergistic interactions with FLU, and toxicity profiles were evaluated against FLU-susceptible and -resistant C. albicans strains.</p><p><strong>Results: </strong>IBU-Na and KET-Na exhibited inhibitory and fungicidal activities against both FLU-susceptible and -resistant C. albicans strains, whereas IM-Na was inactive. Combination assays revealed strong synergistic interactions with FLU (FICI = 0.008-0.009), resulting in marked reductions in fungal viability. Neither hemolytic activity nor genotoxic effects were detected at the tested concentrations.</p><p><strong>Conclusions: </strong>Water-soluble NSAID salts, particularly IBU-Na, demonstrate potent synergistic antifungal activity with FLU and favorable safety profiles, supporting their potential as candidates for antifungal drug repurposing. These findings emphasize the importance of reassessing sodium salt derivatives rather than assuming equivalence with their acidic precursors.</p>","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":"34 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13530096/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148863793","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}