Current pharmaceutical design最新文献

{"title":"Comprehensive Evaluation of Triptolide's Therapeutic Mechanisms in Diabetic Kidney Disease via Meta-Analysis, Network Pharmacology, Molecular Docking, and Mendelian Randomization.","authors":"Jing Ni, Siyuan Song, Yi Wei, Qiling Zhang, Wei Li, Jiangyi Yu","doi":"10.2174/0113816128367671250714100708","DOIUrl":"https://doi.org/10.2174/0113816128367671250714100708","url":null,"abstract":"<p><strong>Introduction: </strong>Diabetic kidney disease (DKD) is a devastating complication of diabetes for which there are few potent treatments.Triptolide (TP), an active compound from Tripterygium wilfordii, has shown potential in early studies, but its therapeutic mechanisms in DKD are not fully understood. This study aims to systematically evaluate TP's efficacy and mechanisms using meta-analysis, network pharmacology, molecular docking, and Mendelian randomization (MR).</p><p><strong>Methods: </strong>A comprehensive search across Chinese and English databases identified animal randomized controlled trials (RCTs) assessing the effects of TP on DKD. A total of 27 studies were incorporated, and a metaanalysis was conducted via Review Manager. TP's drug and disease targets were identified through network pharmacology and molecular docking, while bioinformatics methods were employed to explore the mechanisms. MR analysis was performed to assess potential causal relationships between TP and DKD-related targets.</p><p><strong>Results: </strong>Meta-analysis showed that TP significantly reduced urinary protein, blood lipids, and glucose levels, while improving renal function, renal weight, and renal index (all p < 0.05). Seven core targets-IFNG, CXCL8, TNF, TGFB1, IL2, IL4, and RELA-were identified via network pharmacology, involving key pathways such as lipid-atherosclerosis, AGE-RAGE, and IL-17 signaling. Molecular docking demonstrated strong binding affinities between TP and these targets, with binding energies below -7.00 kJ/mol. Although MR analysis did not establish direct causal relationships between these core genes and DKD, a significant negative correlation between TNF, IL4, and GFR was observed, suggesting their involvement in DKD progression.</p><p><strong>Discussion: </strong>TP may exert therapeutic effects on DKD through coordinated regulation of immune and inflammatory pathways. The integration of multi-omics approaches supports its multi-target pharmacological mechanisms. Although MR analysis did not confirm direct causal relationships, the identified gene associations further reinforce the potential biological relevance of TP. However, this study was primarily based on public datasets and lacks experimental validation in vivo and in vitro.</p><p><strong>Conclusion: </strong>TP exerts therapeutic effects on DKD through multi-target and multi-pathway mechanisms, primarily involving immunomodulation, anti-inflammation, anti-oxidation, and anti-fibrosis processes.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144706617","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":"Comprehensive Meta-Analysis on the Impact of the MDM2 SNP 309 T>G Gene Variant in Leukemia Susceptibility.","authors":"Tarika Naik, Henu Kumar Verma, Madhubala Mulkalwar, Dinesh Mishra, Lvks Bhaskar","doi":"10.2174/0113816128368759250527073556","DOIUrl":"https://doi.org/10.2174/0113816128368759250527073556","url":null,"abstract":"<p><strong>Introduction: </strong>Genetic factors play a significant role in the development of leukemia. The overexpression of MDM2 is associated with the progression of certain leukemias. This meta-analysis investigates the relationship between the MDM2 SNP 309T>G and various forms of leukemia across global populations.</p><p><strong>Methods: </strong>A comprehensive literature search was conducted to retrieve genotyping data from twenty casecontrol studies related to MDM2 SNP 309T>G polymorphism and leukemia. A random-effects model was used to calculate the pooled odds ratio (OR) and 95% confidence interval (95% CI) for the association analysis. MetaGenyo software was utilized to conduct statistical analyses in this meta-analysis.</p><p><strong>Results: </strong>The findings indicate a significant association between MDM2 309 SNPT>G polymorphism and leukemia in Asian and Caucasian populations. Additionally, this polymorphism is associated with an increased risk of Acute Myeloid Leukemia (AML) and Chronic Myeloid Leukemia (CML), implying that MDM2 may play a role in the pathogenesis of these specific forms of leukemia.</p><p><strong>Conclusion: </strong>This meta-analysis suggests that MDM2 may represent a susceptibility gene for leukemia risk.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144706618","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":"Angiogenesis and Resistance Mechanisms in Glioblastoma: Targeting Alternative Vascularization Pathways to Overcome Therapy Resistance.","authors":"Ozal Beylerli, Ilgiz Gareev, Elmar Musaev, Tatiana Ilyasova, Sergey Roumiantsev, Vladimir Chekhonin","doi":"10.2174/0113816128367551250703122830","DOIUrl":"https://doi.org/10.2174/0113816128367551250703122830","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;Glioblastoma (GBM), the most aggressive form of primary brain tumor in adults, remains a significant clinical challenge due to its high recurrence and poor prognosis. Characterized by rapid growth, invasiveness, and resistance to therapy, GBM relies on a sophisticated vascular network to sustain its progression. Angiogenesis, the process of forming new blood vessels, is central to meeting the metabolic demands of the tumor. To address this issue, there is a growing consensus on the need for multi-pronged therapeutic strategies that not only inhibit angiogenesis but also disrupt alternative neovascular mechanisms. Promising approaches include combining anti-angiogenic drugs with agents targeting pathways like neurogenic locus notch homolog protein (NOTCH), Wnt, and C-X-C motif chemokine receptor 4 (CXCR4)/stromal cellderived factor 1 alpha (SDF-1α) to impede vessel co-option, VM, and GSC trans-differentiation.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;The search strategy consisted of using material from the PubMed data, focusing on key terms such as: \"angiogenesis\", \"glioblastoma\", \"glioma\", \"oncogenesis\", \"anti-VEGF treatment\", \"signaling pathways\", \"hypoxia\", \"vessels\", \"resistance\", and \"neurosurgery.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Аs a result of the analysis of existing recent studies, GBM exhibits an adaptive capacity to utilize various neovascular mechanisms, including vessel co-option, vasculogenic mimicry (VM), and the transdifferentiation of glioma stem cells (GSCs) into vascular-like structures, to circumvent traditional antiangiogenic therapies. Initial successes with anti-angiogenic treatments targeting vascular endothelial growth factor (VEGF) showed improvements in progression-free survival. Still, they failed to significantly impact the overall survival due to the tumor's activation of compensatory pathways. Hypoxia, a critical driver of angiogenesis, stabilizes hypoxia-inducible factors (HIF-1α and HIF-2α), which upregulate pro-angiogenic gene expression and facilitate adaptive neovascular responses. These adaptations include vessel co-option, where tumor cells utilize pre-existing vasculature, and VM, where tumor cells form endothelial-like channels independent of typical angiogenesis. Moreover, the role of GSCs in forming new vascular structures through transdifferentiation further complicates treatment, enabling the tumor to maintain its blood supply even when VEGF pathways are blocked.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Discussion: &lt;/strong&gt;This review highlights the necessity for comprehensive and targeted treatment strategies that encompass the full spectrum of neovascular mechanisms in GBM. Such strategies are crucial for developing more effective therapies that can extend patient survival and improve overall treatment outcomes.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;To address the challenge of understanding tumor angiogenesis and ways to inhibit it, there is a growing consensus on the need for multifaceted therapeutic strat","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144689408","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":"Loss of CD99L2 Contributed to Temozolomide Resistance and Glioblastoma Tumorigenesis Based on Genome-scale CRISPR/Cas9 Screening.","authors":"Zeen Sun, Mengke Cui, Zenghao Deng, Lu Zhou, Feiyue Zeng, Zhaoqian Liu, Yingzi Liu","doi":"10.2174/0113816128386002250701113848","DOIUrl":"https://doi.org/10.2174/0113816128386002250701113848","url":null,"abstract":"<p><strong>Introduction: </strong>Glioblastoma Multiforme (GBM) is a highly aggressive and fatal brain malignancy, with Temozolomide (TMZ) serving as the first-line chemotherapeutic treatment. However, over 50% of patients do not respond to TMZ, and the underlying mechanisms remain unclear. This study utilized the GeCKO library to identify novel genes involved in TMZ resistance and to explore their functions.</p><p><strong>Methods: </strong>Loss-of-function genes related to TMZ resistance in GBM cells were identified using the GeCKO library and Next-Generation Sequencing (NGS), validated by qPCR and CCK-8 assays. CD99L2 function was assessed through proliferation, migration, and EdU assays in U251 and U87 cells. Tumor samples from 55 stage IV GBM patients were analyzed to explore the correlation between CD99L2 expression and Progression- Free Survival (PFS).</p><p><strong>Results: </strong>GeCKO library screening identified seven genes associated with TMZ resistance. After validation, CD99L2 was confirmed as a key contributor to TMZ resistance. Knockdown of CD99L2 increased the IC50 of U251 and U87 cells by 1.39- and 1.54-fold, respectively. Conversely, CD99L2 overexpression reduced the IC50 by 0.52- and 0.58-fold. CD99L2 knockdown also promoted tumor proliferation and aggressiveness. Additionally, higher CD99L2 expression was associated with longer PFS in GBM patients (median PFS: 7.87 months vs. 2.7 months, P=0.0003).</p><p><strong>Discussion: </strong>The functions of CD99L2 remain poorly understood. A few studies have reported that CD99L2 may serve as an adhesion molecule modulating inflammatory responses. One study has shown that CD99L2 is highly expressed in the brain and affects neuronal excitability. These findings suggest that CD99L2 may play a positive role in the body's defense against glioma.</p><p><strong>Conclusion: </strong>This study demonstrated that CD99L2 knockdown promotes TMZ resistance and tumorigenesis in GBM, suggesting its potential as a novel biomarker for TMZ resistance.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144682189","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":"Lipid-Based Nanocarriers as a Promising Delivery System in the Management of Acne.","authors":"Soumya Ranjan Masanta, Neha Nilam, Abhisek Pal, Biswakanth Kar, Priyanka Dash, Deepak Pradhan, Jitu Halder, Chandan Das, Vineet Kumar Rai, Saroj Kumar Rout, Goutam Ghosh, Goutam Rath","doi":"10.2174/0113816128404408250707111455","DOIUrl":"https://doi.org/10.2174/0113816128404408250707111455","url":null,"abstract":"<p><strong>Introduction: </strong>Acne vulgaris is a prevalent dermatological condition resulting from inflammation, follicular hyperkeratinization, and bacterial growth. Standard treatments, whether topical or oral, frequently encounter challenges such as limited skin penetration, drug instability, and undesirable side effects. The report found that lipid-based nanocarriers have emerged as a promising alternative, demonstrating the potential for enhanced therapeutic effectiveness, better skin bioavailability, controlled drug release, and targeted delivery specifically to sebaceous glands, which help minimize systemic side effects.</p><p><strong>Aim: </strong>This review article aims to explore the therapeutic potential of various lipid nanocarriers, including Solid Lipid Nanoparticles (SLNs), Nanostructured Lipid Carriers (NLCs), liposomes, microemulsions, niosomes, and ethosomes particularly by examining the mechanisms through which they penetrate the stratum corneum and deeper skin layers to enhance drug delivery.</p><p><strong>Methodology: </strong>This review comprehensively surveys lipid-based nanocarriers for acne vulgaris treatment, drawing from a systematic literature search across Google Scholar, Science Direct, Scopus, Web of Science, and PubMed for publications between 2015 and 2025. The search strategy employed keywords such as \"lipid nanocarrier,\" \"acne vulgaris,\" \"animal models,\" or \"preclinical studies,\" and \"clinical trials\" to capture the research landscape.</p><p><strong>Results: </strong>The review compiles evidence from multiple preclinical experiments and clinical trials regarding the effectiveness of lipid nanocarriers in managing acne. It explores the different pathways these lipid nanocarriers use to permeate the skin and reach target sites. Additionally, it also covers different patents filed by various researchers focusing on the application of lipid nanocarriers for acne management.</p><p><strong>Conclusion: </strong>Lipid nanocarriers represent a significant advancement in dermatological drug delivery, particularly for acne management. By leveraging various skin penetration mechanisms to improve drug targeting to the pilosebaceous unit, they offer potential for more effective treatment compared to conventional methods. While promising, ongoing research and development are necessary to overcome current limitations and fully harness the potential of lipid nanocarriers in clinical practice.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144674083","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":"Single-Cell Transcriptome and Microbiome Profiling Uncover Ileal Immune Impairment in Intrauterine Growth-Retarded Piglets.","authors":"Yiwen He, Yawei Guo, Xuqing Liang, Hong Hu, Xia Xiong, Xihong Zhou","doi":"10.2174/0113816128411269250707073647","DOIUrl":"https://doi.org/10.2174/0113816128411269250707073647","url":null,"abstract":"<p><strong>Introduction: </strong>Impaired intestinal immune function is commonly observed in neonates with intrauterine growth retardation (IUGR), yet its underlying mechanisms and regulatory pathways remain poorly understood. Therefore, we aimed to investigate gene regulatory patterns and microbiota alterations in IUGR piglets.</p><p><strong>Methods: </strong>Three newborn IUGR piglets and three normal littermates were selected from the same sow and sacrificed at seven days of age. Ileal digesta was collected for 16S rRNA amplicon sequencing (16S-seq), and ileum segments were dissociated for single-cell RNA sequencing (scRNA-seq).</p><p><strong>Results: </strong>The scRNA-seq results revealed a reduced proportion of plasma B cells in IUGR piglets, along with alterations in the distribution of various T cell subsets. KEGG pathway analysis further indicated a downregulation of the B cell receptor signaling pathway in B cells from IUGR piglets. In contrast, both the T cell receptor signaling pathway and antigen processing and presentation were attenuated in T cells. Pseudotime trajectory analysis suggested that the differentiation of B cells was impaired in IUGR piglets. SCENIC analysis revealed that GATA3, IRF2, and BCL11A were downregulated in T cells of IUGR piglets. The 16S-seq results revealed that α-diversity was lower in IUGR piglets. At the genus level, the relative abundance of <i>Prevotella</i> was significantly lower in IUGR piglets.</p><p><strong>Discussion: </strong>Significant changes were identified in the proportions of B and T cells, their associated signaling pathways, and intestinal microbiota composition in IUGR piglets, suggesting underlying immune dysfunction and dysbiosis.</p><p><strong>Conclusion: </strong>We identified novel immune-related transcription factors and key microbes as potential therapeutic targets, shedding light on strategies for preventing and treating IUGR.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144674084","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":"Development of Chitosan-Coated Liposomes for Oral Delivery of Nadolol: Preparation, Characterization, and <i>in vitro</i> Permeability Studies.","authors":"Esra İpekci, Emre Şefik Çağlar, Mustafa Sinan Kaynak, Evren Gündoğdu, Neslihan Üstündağ Okur","doi":"10.2174/0113816128401910250706133608","DOIUrl":"https://doi.org/10.2174/0113816128401910250706133608","url":null,"abstract":"<p><strong>Introduction: </strong>This study aims to enhance the oral bioavailability of Nadolol (NDL), a β-blocker used in the management of hypertension, by incorporating it into a liposome-based delivery system. To improve the formulation's stability, mucoadhesion, and permeability, chitosan coating was applied.</p><p><strong>Methods: </strong>Liposomes were prepared via the ethanol injection method using soy phosphatidylcholine and diacetyl phosphate. Chitosan coating was applied by adding chitosan solution (1% v/v acetic acid) at different chitosan-to-lipid ratios (0.1-0.4 w/w). The optimal formulation was selected based on particle size, PDI, and zeta potential. Characterization included encapsulation efficiency, drug loading, enzymatic stability, drug release, and Caco-2-based cytotoxicity and permeability assays.</p><p><strong>Results: </strong>The particle size and polydispersity index of the optimized formulations, L1-NDL, L2-NDL, L1C-NDL, and L2C-NDL, were measured as 27.02 ± 0.18 nm, 24.55 ± 0.22 nm, 160.10 ± 3.17 nm, 161.00 ± 2.30 nm, 0.39 ± 0.01, 0.37 ± 0.01, 0.19 ± 0.01, and 0.18 ± 0.02. Encapsulation efficiencies of 56.01 ± 3.70% and 43.87 ± 1.24% were recorded for L1C-NDL and L2C-NDL, respectively, while drug loading capacities were 61.47 ± 2.03% and 67.80 ± 0.74%, respectively. In an enzymatic degradation study, it was found that chitosan coating increased the stability of liposomes in the gastric media. The <i>in vitro</i> release was higher at both pH 1.2 and 6.8. Caco-2 assays confirmed >95% cell viability and enhanced permeability in the apical-tobasolateral direction. In the permeability study, chitosan-coated liposomal formulations demonstrated enhanced transport in the apical-to-basolateral direction, indicating improved intestinal permeability.</p><p><strong>Conclusion: </strong>Chitosan-coated liposomes improved NDL's stability and permeability, showing promise as an effective oral delivery system.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144658646","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":"Advances in Protein and Polypeptide Drug Analytics.","authors":"Yuanli Mei, Hongmin Liu","doi":"10.2174/0113816128355706250626053659","DOIUrl":"https://doi.org/10.2174/0113816128355706250626053659","url":null,"abstract":"<p><p>With the rapid advancement of biotechnology, protein and peptide drugs have become increasingly widespread in the medical field, yet their metabolic processes are complex and require the assistance of modern analytical methods for research. Based on the latest domestic and international research, this paper systematically reviews the application of modern analytical methods in the metabolism of protein and peptide drugs. The research focuses on key technologies such as biological activity detection, mass spectrometry, and chromatography, elaborating on their principles, characteristics, and current state of development. The aim is to provide scientific evidence and technical support for drug development, and to promote in-depth research on the metabolism of protein and peptide drugs.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144658645","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":"Neuroprotective Effects of Thymol-Loaded Selenium Nanoparticles Against 6-OHDA-Induced Apoptosis and Oxidative Stress in an In Vitro Parkinson's Disease Model.","authors":"Farzaneh Abbasinezhad-Moud, Matin Shirazinia, Raheleh Mirzabeyki, Elham Einafshar, Mohaddeseh Sadat Alavi, Sayeh Shaban, Elaheh Gheibi, Afsane Bahrami","doi":"10.2174/0113816128380006250630103711","DOIUrl":"https://doi.org/10.2174/0113816128380006250630103711","url":null,"abstract":"<p><strong>Introduction: </strong>Parkinson's disease (PD) is characterized by the degeneration of dopaminergic neurons within the substantia nigra, leading to progressive motor dysfunction. There are still limited diseasemodifying options that counteract the process of disease progression. This study aimed to evaluate the neuroprotective effects of thymol, both in its free form and when loaded onto selenium nanoparticles (SeNPs), in a 6-hydroxydopamine (6-OHDA)-induced PD model using SH-SY5Y cells.</p><p><strong>Method: </strong>SeNPs were synthesized using a chemical reduction method with ascorbic acid, achieving a 68% entrapment efficiency for thymol. FTIR analysis suggested an interaction between thymol and selenium, which was confirmed by EDX analysis. Nano-Se-thymol particles were observed to be spherical, with a mean size of 135.7 nm and a negative surface charge.</p><p><strong>Results: </strong>Nano-Se-thymol exhibited low toxicity in normal fibroblast cells and demonstrated greater neuroprotective effects against 6-OHDA-induced cytotoxicity compared to thymol. Nano-Se-thymol significantly reduced ROS generation and increased cell viability compared to 6-OHDA. Furthermore, Nano-Se-thymol decreased the expression of NF-κB inflammatory markers and caspase-3 apoptotic proteins, which were elevated by 6-OHDA, compared to thymol alone.</p><p><strong>Discussion: </strong>Nano-Se-Thymol significantly attenuates 6-OHDA-induced cytotoxicity in an established in vitro model of PD. The neuroprotective efficacy of Nano-Se-Thymol is attributed to its enhanced antioxidant capacity, as evidenced by a significant reduction in ROS levels, along with its ability to inhibit apoptosis and modulate cell cycle progression.</p><p><strong>Conclusions: </strong>Nano-Se-thymol is a potential disease-modifying agent for the treatment of PD; however, further studies and long-term safety assessments are essential to confirm these benefits and understand the underlying mechanisms.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144658647","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":"Development and Optimization of Polyelectrolyte Complex Stabilized Piperine Adjuvant Simvastatin Nanoformulations for Improved Therapeutic Effect.","authors":"Shristy Verma, Sonali Sundram, Mohammad Yusuf, Musarrat Husain Warsi, Rishabha Malviya","doi":"10.2174/0113816128382527250625165648","DOIUrl":"https://doi.org/10.2174/0113816128382527250625165648","url":null,"abstract":"<p><strong>Introduction: </strong>The aim of the study was to prepare polyelectrolyte complex stabilized piperine adjuvant simvastatin nanoformulations and evaluate the antimicrobial effect. Simvastatin has antimicrobial properties but low therapeutic efficacy due to rapid metabolism, with only 12% oral bioavailability. Piperine, a CYP3A4 inhibitor, enhances bioavailability by inhibiting drug-metabolizing enzymes. This study developed chitosan-neem gum polyelectrolyte complex (Ch-NG PEC) nanoparticles combining piperine and simvastatin and evaluated their antimicrobial efficacy compared to simvastatin alone.</p><p><strong>Methods: </strong>A flower-shaped nanoparticles of piperine adjuvant simvastatin were prepared by using chitosan (Ch)-neem gum (NG) as a polyelectrolyte complex (PEC) forming agent, and the anti-microbial effect of nanoformulations with and without piperine was evaluated. A solvent-anti-solvent method was used to form the nanoparticles, and a 32-factorial design was employed to analyze the impact of chitosan and neem gum concentration on the size of the nanoparticles and entrapment efficiency of simvastatin and piperine followed by their release profile and kinetics.</p><p><strong>Results: </strong>Nanoparticles showed high drug entrapment efficiency (simvastatin: 96.4-99.7%, piperine: 64.8- 99.4%) with sizes ranging from 341.3-629.1 nm. Drug release exceeded 50% in 3 hours and 99% in 8 hours, following Hixon-Crowell and Baker's Lonsdale models. Antimicrobial assays revealed activity against Staphylococcus aureus but not Candida albicans. The results of the anti-microbial assay indicated that the PECbased NPs stabilized piperine adjuvant simvastatin showed anti-microbial activity against Staphylococcus aureus but did not exhibit anti-fungal activity against Candida albicans.</p><p><strong>Conclusion: </strong>Piperine-adjuvant simvastatin Ch-NG-PEC nanoparticles demonstrate potential as a dualtreatment agent for hypercholesterolemia and bacterial infections.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144648793","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}