Pharmaceuticals最新文献

{"title":"Exploring Potential for Repurposing Antiretroviral Drugs Etravirine and Efavirenz in Prostate and Bladder Cancer.","authors":"Mariana Pereira, Nuno Vale","doi":"10.3390/ph18091404","DOIUrl":"10.3390/ph18091404","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Prostate and bladder cancers are significant global health challenges with increasing incidence and limited treatment options in advanced stages. Drug repurposing offers a cost-effective strategy to accelerate the development of new anticancer therapies. This study investigated the antitumor activity of the non-nucleoside reverse transcriptase inhibitors efavirenz (EFV) and etravirine (ETV) in prostate and bladder cancer models. <b>Methods:</b> PC-3 prostate cancer and UM-UC-5 bladder cancer cell lines were treated with EFV, ETV, or their combination. Cell viability was assessed at 24, 48, and 72 h to evaluate time and concentration-dependent effects. Wound-healing assays were used to measure cell migration, and clonogenic assays assessed long-term proliferative capacity. <b>Results:</b> Both EFV and ETV decreased cell viability in a time and dose-dependent manner. ETV showed greater potency in PC-3 cells, while EFV demonstrated more consistent effects in UM-UC-5 cells. Combination treatment enhanced cytotoxicity, particularly at 48 and 72 h, suggesting potential synergy. Wound-healing assays indicated impaired migration in UM-UC-5 cells treated with ETV or the EFV + ETV combination. Clonogenic assays confirmed reduced long-term proliferation in both cell lines following treatment. <b>Conclusions</b>: EFV and ETV exhibit selective anticancer activity in prostate and bladder cancer cells, with enhanced effects when combined. These findings support their potential as repurposed therapeutic agents and warrant further preclinical evaluation for prostate and bladder cancer therapy.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 9","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12472435/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145177651","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunoregulation by ESAT-6: From Pathogenesis of Tuberculosis to Potential Anti-Inflammatory and Anti-Rejection Application.","authors":"Weihui Lu, Jingru Lin, Yuming He, Bin Yang, Feifei Qiu, Zhenhua Dai","doi":"10.3390/ph18091408","DOIUrl":"10.3390/ph18091408","url":null,"abstract":"<p><p>The early secreted antigenic target of 6 kDa (ESAT-6), a main effector molecule of the ESX-1 secretion system, is identified as a virulence determinant and immunoregulatory protein of <i>Mycobacterium tuberculosis</i> (Mtb), affecting the interaction between host immune cells and pathogens. ESAT-6 facilitates the survival of mycobacteria and their cell-to-cell spreading through membrane-permeabilizing activity and the regulation of host immune cell functions. In this review, we first summarize the recent knowledge of the roles of ESAT-6 in the survival of bacteria, phagosomal escape, and pathogenicity during Mtb infection. Then, we focused on its complex immunomodulatory effects on different immune cells, such as macrophages, dendritic cells, neutrophils, and T cells, accentuating its capability to either facilitate or inhibit immune responses through different signaling pathways. While our review has summarized its main roles in immunopathology in the context of tuberculosis, we additionally search for emerging evidence indicating that ESAT-6 has anti-inflammatory and immunosuppressive properties. Particularly, we discuss recent preclinical studies showing its capability to suppress transplant rejection and alloimmunity, probably via the induction of regulatory T cells. Nevertheless, the potential clinical use of ESAT-6 remains uncertain and needs further verification by comprehensive preclinical and clinical studies. Thus, we propose that ESAT-6 may be exploited to ameliorate immunopathology in TB infection and to suppress immune-mediated inflammation or transplant rejection as well.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 9","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12472928/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145177728","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Somatic Mutations in DNA Mismatch Repair Genes, Mutation Rate and Neoantigen Load in Acute Lymphoblastic Leukemia.","authors":"Diana Karen Mendiola-Soto, Laura Gómez-Romero, Juan Carlos Núñez-Enríquez, Janet Flores-Lujano, Elva Jiménez-Hernández, Aurora Medina-Sansón, Vilma Carolina Bekker-Méndez, Minerva Mata-Rocha, María Luisa Pérez-Saldívar, David Aldebarán Duarte-Rodríguez, José Refugio Torres-Nava, José Gabriel Peñaloza-González, Luz Victoria Flores-Villegas, Raquel Amador-Sánchez, Martha Margarita Velázquez-Aviña, Jorge Alfonso Martín-Trejo, Laura Elizabeth Merino-Pasaye, Karina Anastacia Solís-Labastida, Rosa Martha Espinosa-Elizondo, Carlos Jhovani Pérez-Amado, Didier Ismael May-Hau, Omar Alejandro Sepúlveda-Robles, Haydee Rosas-Vargas, Juan Manuel Mejía-Aranguré, Silvia Jiménez-Morales","doi":"10.3390/ph18091405","DOIUrl":"10.3390/ph18091405","url":null,"abstract":"<p><p><b>Background/Objectives</b>: During cancer development, tumor cells accumulate somatic mutations, which could generate tumor-specific neoantigens. The aberrant protein can be recognized by the immune system as no-self, triggering an immune response against cells expressing this aberrant protein which could mediate tumor control or rejection. Since the expression of this mutated protein is exclusive to tumor cells, great efforts are being made to identify neoantigens of relevance in the development of new cancer treatment strategies. In comparison to adulthood tumors, pediatric malignancies present fewer mutations and thus fewer potential neoantigens. Acute lymphoblastic leukemia (ALL) is the most common pediatric malignancy worldwide that can be benefited by the identification of neoantigens for immunotherapy approaches, the landscape of neoantigens in ALL is not well known, therefore the aim of our study was to identify potential neoantigens in ALL pediatric patients. <b>Methods</b>: To identify neoantigens in ALL, whole-exome sequencing of matched tumor-normal cells from pediatric cases was performed, with these data HLA-I alleles predicted and somatic mutations identified to propose potential neoantigens based on binding affinity of mutated peptide-HLA-I. <b>Results</b>: We found a strong correlation between tumor mutational burden (TMB) and neoantigen load (<i>p</i> < 0.001) but no correlation with prognosis. Furthermore, TMB and neoantigens were greater in ALL patients with at least one mutated DNA mismatch repair gene (<i>p</i> < 0.001). Also, differences between B- and T-cell ALL were found but statistical significance did not remain after permutation. <b>Conclusions</b>: The presence of neoantigens in pediatric cases with ALL makes the neoantigen-based immunotherapy a promising new strategy for the treatment of this malignancy, especially for patients with relapse.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 9","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12472650/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145177754","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Critical Considerations in the Interpretation of Bone Turnover Marker Data in Hormonal Contraceptive Users. Comment on Tassi et al. Hormonal Contraception and Bone Metabolism: Emerging Evidence from a Systematic Review and Meta-Analysis of Studies on Post-Pubertal and Reproductive-Age Women. <i>Pharmaceuticals</i> 2025, <i>18</i>, 61.","authors":"Jonathan Douxfils, Jean-Michel Foidart","doi":"10.3390/ph18091401","DOIUrl":"10.3390/ph18091401","url":null,"abstract":"<p><p>In response to the recent meta-analysis by Tassi et al. on hormonal contraception and bone metabolism, we raise critical concerns regarding the interpretation of bone turnover markers as surrogates for bone mineral density (BMD). While bone turnover markers can offer early insights into bone remodeling, they do not directly predict long-term BMD changes, which require 12-24 months to detect. The assumption that equivalent percentage changes in bone formation and resorption markers reflect stable BMD is not supported by current evidence. Bone metabolism varies significantly across life stages, particularly during adolescence and early adulthood, when peak bone mass is still accruing-underscoring the need for age-specific analyses. Additionally, biomarker interpretation is limited by assay variability, inconsistent sampling protocols, and uncertain clinical implications, especially for formation markers. Mechanistically, estrogen supports bone integrity by inhibiting resorption and promoting formation; thus, combined hormonal contraceptives (CHCs) containing estrogen may help preserve bone health. In contrast, progestin-only methods can suppress endogenous estrogen production, potentially compromising skeletal development. We advocate for longitudinal studies incorporating both BMD and turnover markers, stratified by age and contraceptive formulation, to guide safer and more informed contraceptive choices that protect long-term bone health.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 9","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12472388/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145177616","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reply to Douxfils, J.; Foidart, J.-M. Critical Considerations in the Interpretation of Bone Turnover Marker Data in HormonalContraceptive Users. Comment on \"Tassi et al. Hormonal Contraception and Bone Metabolism: Emerging Evidence from a Systematic Review and Meta-Analysis of Studies on Post-Pubertal and Reproductive-Age Women. <i>Pharmaceuticals</i> 2025, <i>18</i>, 61\".","authors":"Alice Tassi, Ambrogio P Londero, Anjeza Xholli, Giulia Lanzolla, Serena Bertozzi, Luca Savelli, Federico Prefumo, Angelo Cagnacci","doi":"10.3390/ph18091402","DOIUrl":"10.3390/ph18091402","url":null,"abstract":"<p><p>Dear Editor, [...].</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 9","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12472703/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145177629","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sinapic Acid Regulates the LXRα-ABCG5/8 Axis in the Hepatocytes: A Potential Strategy for Cholesterol Gallstone Management.","authors":"Sridevi Rajendran, Chitra Vellapandian, Bhupendra G Prajapati, Himanshu Paliwal","doi":"10.3390/ph18091388","DOIUrl":"10.3390/ph18091388","url":null,"abstract":"<p><p><b>Background/Objective:</b> Gallstone disease (cholelithiasis) is a prevalent hepatobiliary disorder with limited non-surgical therapeutic options. Sinapic acid (SINAP), a phenolic compound found in various dietary sources, has demonstrated anti-inflammatory and hepatoprotective effects. However, its role in gallstone dissolution has not been explored. This study was designed to evaluate whether sinapic acid modulates hepatic cholesterol transport and enhances gallstone dissolution using a gallstone dissolution assay in artificial bile solution. <b>Methods:</b> The cytotoxicity of SINAP was assessed in HepG2 cells via the MTT assay. The mRNA and protein expression of lipid transporters (ABCG5, ABCG8, and LXRα) was quantified using qRT-PCR, ELISA, and Western blotting. Additionally, molecular docking was conducted to evaluate SINAP's interaction with gallstone-related protein targets compared to that for the standard drugs (ursodeoxycholic acid and ezetimibe). <b>Results:</b> SINAP achieved a 53.71% gallstone weight reduction over 12 days, comparable to that with ursodiol (59.24%), and following 24 h of exposure, SINAP demonstrated minimal cytotoxicity, maintaining over 80% cell viability up to 50 µg/mL, with an IC₅₀ value of 28 µg/mL. SINAP significantly upregulated ABCG5, ABCG8, and LXRα expression (<i>p</i> < 0.01), suggesting enhanced bile acid secretion. Docking studies confirmed the strong binding affinities of SINAP to key cholesterol transport proteins. <b>Conclusions:</b> These results indicate that SINAP may serve as a promising natural candidate for non-surgical management of cholelithiasis and support further preclinical investigation.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 9","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12473006/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145177671","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Study on the Physical Properties and Application of a Novel Pharmaceutical Excipient Made from Starch and Cellulose Co-Processing.","authors":"Yong Bi, Hanfang Lei, Ying Fang, Simeng Wang, Jihui Tang","doi":"10.3390/ph18091389","DOIUrl":"10.3390/ph18091389","url":null,"abstract":"<p><p><b>Objective:</b> This article investigated the structural characteristics, powder properties, and performance variations of co-processed pregelatinized starch (PS) and microcrystalline cellulose (MCC) at varying ratios. <b>Methods:</b> Scanning Electron Microscopy (SEM) revealed the embedding of MCC within the PS matrix. Fourier-transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD) analysis indicated no chemical interaction between the starch and MCC during processing. The physical properties of the co-processed materials were evaluated using multiple indicators, such as the Carr index, and their properties in pharmaceutical applications were evaluated using multiple indicators, such as tensile strength and dilution capacity. <b>Results:</b>The absence of new chemical substances during co-processing, as confirmed by FTIR/XRD analyses, coupled with SEM evidence of a physically interlocked MCC-PS architecture, conclusively demonstrates that structural reorganization occurred via physical mechanisms.An increase in the MCC proportion enhanced the tensile strength of the co-processed material while decreasing the Carr's index, particle size, tapped density, bulk density, swelling, and water-soluble content. A co-processed sample (PS:MCC = 7:3) was selected for application in formulations. The co-processed material exhibited superior compactibility compared to a physical mixture and demonstrated favorable dilution capacity in poorly compactible model drugs, including Linaoxin and Lingzhi spore powder, as well as higher biological inertness. <b>Conclusions:</b> These findings suggest that the co-processed PS and MCC possess excellent compactibility and dilution capacity. The co-processed excipient demonstrates applicability in direct compression manufacturing of oral solid dosage forms (e.g., tablets), offering distinct advantages for high drug-loading formulations.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 9","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12472847/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145177741","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cardiotoxicity Induced by Anticancer Therapies: A Call for Integrated Cardio-Oncology Practice.","authors":"Giuliana Ciappina, Luigi Colarusso, Enrica Maiorana, Alessandro Ottaiano, Tindara Franchina, Antonio Picone, Gaetano Facchini, Chiara Barraco, Antonio Ieni, Maurizio Cusmà Piccione, Concetta Zito, Massimiliano Berretta","doi":"10.3390/ph18091399","DOIUrl":"10.3390/ph18091399","url":null,"abstract":"<p><p>The introduction of novel oncologic therapies, including targeted agents, immunotherapies, and antibody-drug conjugates, has transformed the therapeutic landscape of cancer care. This evolution has resulted in a dual clinical scenario; while survival outcomes have markedly improved, leading to a growing population of long-term cancer survivors, an increasing incidence of previously unrecognized treatment-related toxicities has emerged. Among these, cardiovascular adverse events represent some of the most prevalent and clinically significant complications observed in both conventional chemotherapy and modern therapeutic regimens. Cardiotoxicity has become a major concern, with the potential to adversely affect not only cardiovascular health but also the continuity and efficacy of oncologic treatments, thereby impacting overall survival. This opinion paper synthesizes current evidence, identifies critical gaps in knowledge, and advocates for a multidisciplinary, evidence-based framework to guide the prevention, early detection, and optimal management of cardiotoxicity associated with anticancer therapies.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 9","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12472877/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145177536","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phlorizin Alleviates Depression-like Behaviors via Gut Microbiota Reprogramming-Induced Methionine to Inhibit Neuroinflammation in Mice Hippocampus.","authors":"Lingling Li, Jianxin Chen, Xinyu Zhang, Xuya Zhang, Yan Fu, Hong Jiang, Tianxing Yin, Yali Zhang, Xue Li, Mengyuan Hu, Yi Lu","doi":"10.3390/ph18091395","DOIUrl":"10.3390/ph18091395","url":null,"abstract":"<p><p><b>Background</b>: Depression is associated to gut microbiota imbalance. Our research examined the antidepressant potential of phlorizin (PHZ), a natural anti-inflammatory compound that influences gut microbiota, and explored its underlying mechanisms. <b>Methods</b>: A corticosterone (CORT)-induced depression mouse model was used for evaluating the ameliorative influences of PHZ on depressive phenotypes and central neuroinflammation through behavioral tests and biochemical assays. 16S rRNA sequencing and metabolomics were used to evaluate gut microbiota composition and metabolite levels in serum and hippocampal tissue, respectively. Spearman correlation and broad-spectrum antibiotic cocktail (ABx) treatment experiments verified the effect of gut microbes in the PHZ-mediated modulation of key metabolites. A lipopolysaccharide (LPS)-induced BV2 microglial inflammation model was established to evaluate the role of metabolites in PHZ's antineuroinflammatory effects. <b>Results</b>: PHZ significantly alleviated depressive-like behaviors in CORT mice and suppressed hippocampal neuroinflammation by modulating microglial M1/M2 polarization. Furthermore, PHZ altered gut microbiota composition, influenced serum methionine (Met) metabolism, and significantly increased hippocampal L-methionine (L-Met) and S-adenosylmethionine (SAMe) levels. Cellular experiments confirmed that L-Met plays a critical role in PHZ-mediated antineuroinflammatory effects. Significant correlations were observed between Parabacteroides, Parasutterella, and Alistipes and serum Met levels. ABx treatment suppressed the increase in hippocampal L-Met levels, suggesting that PHZ regulates methionine metabolism via the microbiota. These findings indicate that PHZ alleviates depressive states in CORT mice by modulating the microbiota-gut-brain axis. <b>Conclusions</b>: PHZ modulates the gut microbiota (namely <i>Parabacteroides</i>, <i>Parasutterella</i>, and <i>Alistipes</i>) and increase L-Met and SAMe levels, thereby suppressing neuroinflammation and improving depressive phenotypes in mice.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 9","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12472783/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145177700","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Influence of PEG Molecular Weight on Washout Resistance and Deposition Efficiency of Magnetoresponsive Nanoclusters Under Pulsatile Flow for Magnetic Drug Targeting.","authors":"Sandor I Bernad, Elena S Bernad","doi":"10.3390/ph18091394","DOIUrl":"10.3390/ph18091394","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Magnetic drug targeting (MDT) using polyethene glycol (PEG)-coated magnetoresponsive nanoclusters (MNCs) can localize therapeutics, but washout from high-shear arterial flow limits efficacy. This study assesses how PEG molecular weight influences MNC deposition and washout resistance under a pulsatile flow. <b>Methods:</b> Magnetite MNCs were synthesized via solvothermal polyol reactions and PEGylated with PEG-2000, PEG-6000, or PEG-10,000. Characterization included TEM, DLS, zeta potential, FTIR, TGA, XPS, magnetic analysis, and rheology. In vitro assays used a 3 mm diameter glass phantom with pulsatile flow (0.10-0.45 m/s, 1 Hz) and a rectangular NdFeB (N35) permanent magnet (30 × 20 × 20 mm, 0.45 T) positioned 11 mm from the vessel wall. Washout performance was quantified by obstruction degree (OD), magnet coverage degree (MCd), washout degree (WD), washout rate constant (k_out), and half-life (τ₁/₂). <b>Results:</b> MNC-6000 balanced magnetic responsiveness (Ms = 72 emu/g), colloidal stability (ζ = +13.1 mV), and hydrodynamic size (535 nm), yielding superior retention (MCd = 72.3%, OD = 19.6%, WD = 17.9%, τ₁/₂ = 6.93 min). MNC-2000 exhibited faster loss (k_out = 0.14 min^-1, τ₁/₂ = 4.95 min), while MNC-10,000 produced higher OD (≈53%) with embolic risk. Magnetic mapping indicated vessel wall thresholds of B ≥ 0.18 T and ∇B ≥ 10 T/m for stable capture. <b>Limitations:</b> Limitations of this work include the use of a single-magnet geometry, an in vitro phantom model without endothelial biology, and a maximum targeting depth of ~12-14 mm. <b>Conclusions:</b> The PEG molecular weight modulates MDT performance through its effects on nanocluster stability, deposition morphology, and washout kinetics. The proposed OD, MCd, and WD metrics provide clinically relevant endpoints for optimizing MDT nanoparticle design and magnet configurations.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 9","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12473000/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145177301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}