Current pharmaceutical design最新文献

{"title":"Machine Learning Analysis of Liposome Stability in Polyol-Tween 85 Surfactant Systems.","authors":"Min Kyung Kang, Hee Charn Lee, Jeong Seon Hwang, Jin-Chul Kim","doi":"10.2174/0113816128508363260804070643","DOIUrl":"https://doi.org/10.2174/0113816128508363260804070643","url":null,"abstract":"<p><strong>Introduction: </strong>Liposomes, bilayered vesicles capable of encapsulating both hydrophilic and hydrophobic compounds, are widely utilized in cosmetic formulations owing to their superior biocompatibility. However, their structural integrity can be compromised by surfactants and polyols, which are essential components in the formulation process. Therefore, it is imperative to evaluate how the concentrations of these additives influence the stability and release behavior of liposomes.</p><p><strong>Method: </strong>To analyze the impact of Tween 85 and five different polyols on liposomal release, second-order multiple linear regression models were developed. Nonlinear interactions were visualized using 3D regression surfaces. Furthermore, K-Nearest Neighbors (KNN), logistic Regression (LR), and Stochastic Gradient Descent (SGD) algorithms were implemented to classify liposomal stability. To enhance the generalization performance of the models, Ridge and LASSO regularization techniques were incorporated.</p><p><strong>Result: </strong>All regression models achieved high predictive accuracy. Notably, the overfitting issues observed in formulations containing 1,2-hexanediol (1,2-HD) and 1,2-octanediol (1,2-OD) were effectively mitigated through the application of Ridge and LASSO models. Among the classification models, the SGD classifier demonstrated the highest accuracy, followed by logistic regression and KNN.</p><p><strong>Discussion: </strong>The results indicated that the concentration of the surfactant (Tween 85) had a more dominant effect on liposomal release behavior than that of polyols. This is consistent with previous findings that surfactants promote the disruption of the membrane structure by increasing the fluidity of the lipid bilayer. The developed models accurately capture the nonlinear interactions between additives, providing a practical predictive tool for formulation optimization.</p><p><strong>Conclusion: </strong>This study systematically classified and predicted liposomal stability under complex conditions involving various concentrations of polyols and surfactants using machine learning algorithms. The developed models are expected to facilitate efficient formulation design in liposome-based systems, including cosmetic and drug delivery applications, by minimizing trial and error.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148808392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting Gut Microbiota and GPX4/xCT Signaling: A Mechanism by Tang Liping Formula Inhibits Pancreatic Ferroptosis in T2DM.","authors":"Lin Guo, Linlin Wang, Wenlan Zhang, Shanshan Huang, Tong Xia, Fayin Huang, Yunong Chen, Yumou Yang, Chunmei Yi, Nairu Yun, Yongna Dai, Huhu Li","doi":"10.2174/0113816128448237260530124456","DOIUrl":"https://doi.org/10.2174/0113816128448237260530124456","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;To explore the potential mechanism of the Chinese formula Tangliping (TLP) in the treatment of T2DM.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;This study employed bibliometric methods to conduct a thematic keyword cluster analysis of the drugs contained in TLP, and combined network pharmacology to explore the related mechanisms of TLP in T2DM. A total of 30 mice were included and divided into 5 groups, including the control group (n=6), model group (n=6), TLP-L group (n=6), TLP-H group (n=5; one mouse died during the experiment), and MET group (n=6). The T2DM mouse models were subsequently established, and the efficacy of TLP in treating T2DM was verified by measuring fasting blood glucose, conducting an oral glucose tolerance test, and assessing blood lipid and serum insulin levels. H&E staining and immunohistochemistry were used to observe damage in colonic and pancreatic tissues. The effect of TLP on intestinal flora was examined via fecal 16S rRNA sequencing. The impacts of TLP on ferroptosis in pancreatic cells of T2DM mice were evaluated by measuring serum levels of GSH and SOD, the immunohistochemical positivity rate of 4-hydroxynonenal (4-HNE) in pancreatic tissue，and by detecting the expression of GPX4, GSH, SLC7A11, FTH1, HO-1, HIF-1α, and NRF2 via RT-qPCR and Western blot. By analyzing data on gut microbiota and ferroptosis-related indicators, a heatmap was generated to reveal the potential association between TLP-mediated gut microbiota regulation and ferroptosis in T2DM.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;The bibliometric and network pharmacology analyses suggested that TLP may exert therapeutic effects on T2DM by modulating the gut microbiota and ferroptosis. Our study demonstrated that TLP reduced fasting blood glucose, improved glucose tolerance and lipid profiles, ameliorated insulin resistance and islet dysfunction, alleviated pancreatic tissue damage, and modulated the abundance and composition of intestinal microbiota in T2DM mice. We found that TLP increased serum levels of SOD and GSH, decreased positivity rates of 4-HNE in mouse islets, upregulated the expression of GPX4, GSH, SLC7A11, FTH1, HO-1, HIF-1α, and NRF2, and downregulated the expression of TFRC. Furthermore, our study found that the Bacteroidota showed a negative correlation with 4-HNE expression, while Desulfobacterota exhibited a positive correlation with 4-HNE expression and a negative correlation with GPX4 expression. And the norank_f__ Desulfovibrionaceae, norank_f__Oscillospiraceae, and Lactobacillus also demonstrated significant correlations with key ferroptosis indicators, including GPX4, GSH, and 4-HNE.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Discussion: &lt;/strong&gt;The global prevalence of type 2 diabetes mellitus (T2DM) continues to rise, posing a serious threat to human quality of life. This study, by integrating pharmacodynamic results, gut microbiota analysis, and mechanism verification, confirmed that TLP can improve the gut microbiota structure in T2DM mi","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148808340","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Designing Photostable Hair Dyes with UV-Blocking Properties: Molecular Docking Approaches for Targeted Hair Protection.","authors":"Shikha Baghel Chauhan, Chirag Jain, Indu Singh","doi":"10.2174/0113816128464711260701164206","DOIUrl":"https://doi.org/10.2174/0113816128464711260701164206","url":null,"abstract":"<p><p>Hair dyeing is an activity that is here to stay, but the challenge of finding dyes that last longer and provide adequate protection from UV radiation is still an area that is difficult to crack. In this paper, the author attempts to survey the current state of the art in the field of finding photostable dyes that can provide adequate protection from UV radiation by discussing the current understanding of the photodegradation of traditional dyes, the current understanding of the photodegradation of dyes, the current understanding of the impact of UV radiation on keratin, and the current understanding of the use of molecular docking as a tool for predicting the effectiveness of dyes in providing adequate protection from UV radiation. The paper attempts to provide a mechanism for the design of the next generation of hair dyes that can provide adequate protection from UV radiation and safety for the consumer. The author of the paper has taken a novel approach in that, unlike other earlier reviews, the author has focused on molecular docking as the tool for predicting the effectiveness of the next generation of dyes in providing adequate protection from UV radiation, unlike other earlier reviews that have focused on describing the characteristics of the formulation of the dye.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148808289","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuroinflammation as a Pharmacological Target in Psychiatric Disorders.","authors":"Pawan N Karwa, Vaibhav Parekar, Sarthak Buttepatil, Nikhil S Sakle","doi":"10.2174/0113816128483031260729072100","DOIUrl":"https://doi.org/10.2174/0113816128483031260729072100","url":null,"abstract":"<p><p>Neuroinflammation is increasingly recognized as a pivotal mechanism linking immune dysregulation with the onset, progression, and treatment resistance of major psychiatric disorders. Once considered distinct from classical neurodegenerative diseases, psychiatric conditions such as Major Depressive Disorder (MDD), schizophrenia, bipolar disorder, and anxiety disorders are now known to involve chronic, low-grade inflammation within the Central Nervous System (CNS). Persistent activation of microglia and astrocytes, together with disruption of Blood-Brain Barrier (BBB) integrity, initiates neurotoxic cascades that alter the balance between pro-inflammatory and anti-inflammatory cytokines. These alterations impair neurotransmission, reduce neuroplasticity, increase oxidative stress, and ultimately contribute to neuronal dysfunction. Several molecular pathways, including Nuclear Factor Kappa B (NF-κB), the NLRP3 inflammasome, and the kynurenine pathway (KP), play central roles in mediating these inflammatory responses. Activation of the KP diverts tryptophan metabolism away from serotonin synthesis toward the production of neuroactive metabolites such as quinolinic acid, thereby promoting excitotoxicity and neurodegeneration. Elevated circulating inflammatory biomarkers, including C-Reactive Protein (CRP), interleukin-6 (IL-6), and Tumor Necrosis Factor- alpha (TNF-α), have been consistently associated with increased disease severity and poor response to conventional monoaminergic therapies. Consequently, pharmacological modulation of neuroinflammation has emerged as a promising therapeutic strategy. Current and emerging approaches include cyclooxygenase-2 (COX-2) inhibitors, cytokine-targeted therapies, modulators of microglial activation, antioxidant agents such as N-acetylcysteine and omega-3 fatty acids, as well as novel therapeutics targeting the NLRP3 inflammasome, P2X7 receptors, and microglial polarization. Furthermore, integrating inflammatory biomarker profiling with advanced neuroimaging techniques, including Translocator Protein Positron Emission Tomography (TSPO-PET), may facilitate patient stratification and enable precision psychiatry. A comprehensive understanding of neuroinflammatory mechanisms may therefore provide new opportunities for developing targeted therapeutic interventions and improving clinical outcomes in psychiatric disorders.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148808419","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and Mechanisms of Yuye Decoction for Diabetic Nephropathy: A Meta-Analysis and In Silico Study.","authors":"Yunyi Yang, Xiaoxiao Qu, Xiaoli He, Jiayuan Cai, Jiawen You, Yanming He, Zheng Yao, Hongjie Yang","doi":"10.2174/0113816128447649260727055109","DOIUrl":"https://doi.org/10.2174/0113816128447649260727055109","url":null,"abstract":"<p><strong>Introduction: </strong>Yuye decoction (YYD), a traditional Chinese medicinal formula, has the potential to improve renal function and alleviate symptoms in diabetic nephropathy (DN). This study aimed to evaluate the potential clinical effects and explore the pharmacological mechanisms of YYD in DN using meta-analysis and in silico approaches.</p><p><strong>Methods: </strong>We conducted a systematic review of randomized controlled trials (RCTs) on YYD for treating DN, searching databases including China National Knowledge Infrastructure (CNKI), SinoMed, Wanfang Data, VIP, PubMed, Embase, Cochrane Library, Web of Science, and Google Scholar, with a cutoff date of June 2025. Eligible RCTs compared YYD combined with standard Western treatment with Western treatment alone. The primary outcome was renal function improvement, while secondary outcomes included overall clinical efficacy, glycemic control, and adverse events. Network pharmacology and molecular dynamics simulations were conducted to explore potential mechanisms.</p><p><strong>Results: </strong>Thirteen RCTs involving 961 patients were included. Compared with conventional treatment alone, YYD combination therapy was associated with reductions in serum creatinine (WMD = -11.64, 95% CI [-19.04, -4.24]), blood urea nitrogen (WMD = -0.59, 95% CI [-0.93, -0.25]), and 24-hour urinary protein excretion (MD = -39.59, 95% CI [-62.07, -17.11]). An increased overall clinical efficacy rate was observed as a secondary outcome (RR = 1.43, 95% CI [1.31, 1.56]). Network pharmacology suggested that YYD may modulate inflammation-, metabolism-, and fibrosis-related pathways via targets such as SRC, PIK3R1, and PIK3CA. Molecular dynamics simulations indicated stable binding between Bifendate and SRC kinase.</p><p><strong>Discussion: </strong>These findings suggest that YYD may exert renoprotective effects through multi-target and multi-pathway mechanisms, particularly involving inflammatory regulation, metabolic processes, and fibrosis inhibition. However, the included studies showed variability in methodological quality and sample size, which may affect the robustness of the conclusions. Furthermore, the in silico results require experimental validation to confirm their biological relevance.</p><p><strong>Conclusion: </strong>YYD combined with conventional therapy may improve renal function in patients with DN. Nevertheless, the overall certainty of the evidence remains limited, and further large-scale, high-quality randomized trials and mechanistic studies are warranted.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148808238","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Designing In-situ Gels for Periodontal Repair: A Review of Sustained Release Strategies, Advanced Manufacturing Approaches, and Bio-Fabrication.","authors":"Ujjawal, Ayush Parker, Jaydeep Singh Baghel, Naveen Singh, Satya Bharti Singh, Divyanshu Tripathi, Shivani Rai Paliwal, Rishi Paliwal","doi":"10.2174/0113816128496130260728090536","DOIUrl":"https://doi.org/10.2174/0113816128496130260728090536","url":null,"abstract":"<p><p>Periodontitis is a chronic biofilm-mediated inflammatory disease that progressively destroys the gingiva, periodontal ligament, and alveolar bone. Although scaling and root planing remain the cornerstone of care, incomplete pocket access, rapid microbial recolonization, and the limited residence time of many conventional local formulations can reduce therapeutic effectiveness. The development of in-situ gelling drug delivery systems, administered as low-viscosity liquids that transform within periodontal pockets into mucoadhesive gels, improves retention, prolongs drug contact time, provides sustained site-specific release, and reduces systemic exposure. In this review, we summarize the rationale for localized therapy in the context of periodontal disease and outline the design space of periodontal in-situ gels. Additionally, thermosensitive, pHresponsive, ion-activated, solvent exchange, enzymatically crosslinked, photosensitive, and multi-responsive platforms are compared. The polymer selection and concentration govern injectability, gelation trigger and time, mechanical integrity, biodegradation, and diffusion-controlled release behavior, with commonly used matrices including chitosan, poloxamers, carbomers, sodium alginate, gellan gum, carrageenan, HPMC, and Eudragit-based systems. We highlight representative formulations delivering antimicrobials, antiseptics, and anti-inflammatory agents, as well as herbal extract-loaded gels. Key evaluation parameters relevant to periodontal pockets are also discussed, together with translational considerations reflected in patents, early clinical investigations, and marketed products. Future directions that integrate multifunctional responsiveness with regenerative cues, including growth factor- or cell-compatible gels and advanced manufacturing approaches such as 3D bioprinting and in-situ bio-fabrication, aimed at personalized periodontal tissue repair and durable control of inflammation are urgently needed.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148807963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Huatuo Zaizao Pills Alleviate Neuroinflammation and Neuronal Apoptosis via Microglial M2 Polarization in a Permanent Cerebral Ischemia Mouse Model.","authors":"Die Deng, Mei-Qi Lu, Ze-An Weng, Jie-Wen Zhou, Nan-Nan Wang, Dan-Ting Peng, Qiu-Ling Huang, Dan Lu, Na Ning, An-Ding Xu","doi":"10.2174/0113816128472276260724223326","DOIUrl":"https://doi.org/10.2174/0113816128472276260724223326","url":null,"abstract":"<p><strong>Introduction: </strong>This study aimed to explore the potential neuroprotective effects of Huatuo Zaizao pills (HTZZ) in modulating microglial polarization-mediated neuroinflammation and apoptosis.</p><p><strong>Materials & methods: </strong>Twenty-four male mice were included in the study. Sixteen mice underwent permanent middle cerebral artery occlusion (pMCAO) and were randomly assigned to either the MCAO group (vehicle, n = 8) or the MCAO+HTZZ group (HTZZ, 5.80 g/kg, n = 8). Eight mice underwent sham surgery and received vehicle treatment (Sham group). HTZZ or vehicle was administered orally for seven days before surgery and continued for three days after surgery. Neurological functions were evaluated using the Longa score, adhesive removal test, grid-walking test, and forelimb grip strength test. Neuronal damage was assessed via Nissl staining and double immunofluorescence staining for postsynaptic density protein 95 (PSD95) and microtubule-associated protein 2 (MAP2). We also quantified pro-inflammatory cytokines as well as markers of microglial polarization. Apoptosis was assessed through both TUNEL assays and Western blot quantification of key apoptosis-associated proteins.</p><p><strong>Results: </strong>When comparing HTZZ-treated and untreated ischemic animals at 72 h after pMCAO, mice receiving HTZZ exhibited notable functional improvement. HTZZ treatment suppressed pro-inflammatory cytokines and decreased GFAP- and Iba-1-positive cells in the peri-infarct area. Analysis of microglial phenotypes revealed that HTZZ diminished the expression of iNOS/Iba-1+ cells while increasing Arg-1/Iba-1+ cells (both P<0.05). HTZZ markedly lowered the proportion of TUNEL-positive profiles and shifted the balance of apoptosis regulators toward higher Bcl-2/Bax ratios.</p><p><strong>Discussion: </strong>These findings suggest that HTZZ may exert neuroprotective effects through modulation of microglial polarization and attenuation of neuroinflammatory responses. By shifting microglia/macrophages away from a pro-inflammatory phenotype and suppressing cytokine overproduction, HTZZ appears to mitigate secondary neuronal injury in the peri-infarct region. The observed reduction in apoptotic markers and restoration of the Bcl-2/Bax balance indicate HTZZ's potential role in inhibiting neuronal apoptosis. Notably, increased Akt phosphorylation was observed, indicating the possible involvement of the PI3K/Akt pathway.</p><p><strong>Conclusion: </strong>HTZZ demonstrates potential neuroprotective effects in permanent cerebral ischemia, possibly through modulation of microglial polarization and attenuation of neuronal apoptosis. These findings support further investigation into HTZZ as a multi-target therapeutic candidate for ischemic stroke.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148808315","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Carvedilol Beyond the Heart: Pleiotropic Mechanisms and Emerging Therapeutic Applications Across Organ Systems.","authors":"Dhirendra Singh, Joy Oladimeji-Salami, Abidemi James Akindele","doi":"10.2174/0113816128489643260728112117","DOIUrl":"https://doi.org/10.2174/0113816128489643260728112117","url":null,"abstract":"<p><p>Carvedilol (CVR) is a nonselective β1- and β2-adrenergic receptor antagonist with additional α1-adrenergic blocking activity, commonly used to treat heart failure, hypertension, and left ventricular dysfunction following myocardial infarction. Beyond its established cardiovascular indications, increasing evidence suggests that CVR exhibits diverse pleiotropic effects, including anticancer, neuroprotective, hepatoprotective, renoprotective, cardioprotective, anti-inflammatory, and anti-arthritic activities. A comprehensive literature search was conducted in Web of Science, PubMed, Scopus, and Google Scholar, including English-language full-text studies reporting preclinical or clinical evidence of CVR's non-cardiovascular therapeutic effects. This review synthesises findings from 167 experimental and clinical studies that evaluate the molecular mechanisms, translational relevance, and therapeutic potential of CVR beyond cardiovascular disease. Current evidence indicates that CVR modulates oxidative stress, inflammation, apoptosis, and multiple cell-survival signalling pathways across diverse organ systems. Although most evidence remains preclinical, the growing body of data highlights CVR as a promising candidate for therapeutic repurposing and warrants further clinical investigation.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148807825","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nanotechnology-Enabled Combination Strategies to Enhance 5-Fluorouracil-Based Cancer Chemotherapy.","authors":"Rohit Sharma, Kaisar Raza, Thakur Gurjeet Singh, Poonam Negi","doi":"10.2174/0113816128474301260616105614","DOIUrl":"https://doi.org/10.2174/0113816128474301260616105614","url":null,"abstract":"<p><p>Cancer still ranks among the top causes of morbidity and mortality across the globe. Among the existing treatment modalities, including surgery, radiation therapy, biological therapy, and chemotherapy, 5-fluorouracil (5-FU) is one of the most widely employed drugs for the treatment of different solid cancers, such as colorectal, breast, pancreatic, and head and neck cancers. Although the drug has proven its efficacy in clinical settings, the therapeutic potential of 5-FU is greatly hampered by its rapid systemic clearance, severe dose-toxicity, lack of selectivity, and development of drug resistance. Therefore, there is a need to develop innovative approaches to improve its therapeutic effectiveness. Recently, nanotechnology has been recognized as a promising tool to address these issues by enhancing the stability, bioavailability, targetability, and controlled release of drugs. Different nanocarriers, such as liposomes, niosomes, nanostructured lipid carriers, solid lipid nanoparticles, hydrogels, polymeric nanoparticles, microparticles, and metal-organic frameworks, have been vastly explored to improve the pharmacokinetic and pharmacodynamic properties of 5-FU. In addition to improving 5-FU delivery, these nanocarriers also offer opportunities for combination therapy and for overcoming drug resistance. This review offers a comprehensive, comparative analysis of nanocarrier-based approaches for 5-FU delivery, focusing on their mechanistic benefits, preclinical efficacy, and translational potential. Moreover, ongoing clinical trials and combination therapies are reviewed to provide a translational perspective on the use of nanotechnology-based 5-FU chemotherapy. Overall, nanocarrier-based delivery offers a promising approach to improve the therapeutic efficacy and safety of 5-FU in cancer treatment.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148808375","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mumio Potentiates Temozolomide by Inducing Apoptosis and Ferroptosis in Glioblastoma Cells.","authors":"Basak Dalbayrak, Zeynep Demirel, Ayşe Şevval Martin, Pınar Uysal Onganer, Pinar Obakan Yerlikaya, Sedat Dalbayrak, Elif Damla Arisan","doi":"10.2174/0113816128484031260604055912","DOIUrl":"https://doi.org/10.2174/0113816128484031260604055912","url":null,"abstract":"<p><strong>Introduction: </strong>Glioblastoma multiforme is an extremely deadly, aggressive primary brain tumor, distinguished by poor prognosis, and the rapid development of resistance to temozolomide might be the cause of low survival. Novel adjunctive strategies are needed to enhance therapeutic efficacy. Mumio (Shilajit), rich in fulvic acid and bioactive compounds, has shown antioxidant and anticancer effects, but its role in glioblastoma remains unclear. This study evaluated its anticancer potential and its ability to enhance temozolomide efficacy.</p><p><strong>Methods: </strong>Mumio extract was tested in U87 (sensitive) and LN-18 (resistant) glioblastoma cell lines. Cell viability and clonogenicity were assessed by MTT and colony formation assays. Fluorescent staining evaluated mitochondrial function, reactive oxygen species, and lipid accumulation. Western blotting analyzed apoptotic (PARP, Caspase-3, PTEN), ferroptosis-related (NRF2, FTH1), and Akt signaling proteins. Combination treatments were also examined.</p><p><strong>Results: </strong>Mumio reduced cell viability in a dose- and time-dependent manner, with stronger effects in U87 cells. It increased reactive oxygen species, disrupted mitochondrial function, and induced apoptosis, as shown by increased cleaved PARP and Caspase-3. Ferroptosis-related changes, including reduced FTH1 in LN-18 cells, were observed. Mumio also enhanced temozolomide-induced cytotoxicity and reduced clonogenic survival.</p><p><strong>Discussion: </strong>These findings suggest that Mumio exerts anticancer effects through oxidative stress-mediated apoptosis and modulation of ferroptosis pathways. Its ability to enhance temozolomide efficacy, particularly in resistant cells, indicates a potential role in overcoming chemoresistance.</p><p><strong>Conclusion: </strong>Mumio triggers apoptosis in glioblastoma cells and induces changes consistent with ferroptosis, while also chemosensitizing cells to temozolomide, suggesting its potential use alongside standard therapy.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148808387","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}