European Journal of Pharmaceutical Sciences最新文献

{"title":"Assessing the effects of tofacitinib on the gut microbiome in inflammatory bowel disease","authors":"Alessia Favaron ,&nbsp;Nannapat Sangfuang ,&nbsp;Laura E. McCoubrey ,&nbsp;Atheer Awad ,&nbsp;Jonas Ghyselinck ,&nbsp;Massimo Marzorati ,&nbsp;Lynn Verstrepen ,&nbsp;Julie De Munck ,&nbsp;Jelle De Medts ,&nbsp;Abdul W. Basit ,&nbsp;Mine Orlu","doi":"10.1016/j.ejps.2025.107365","DOIUrl":"10.1016/j.ejps.2025.107365","url":null,"abstract":"<div><div>Gut microbiota dysbiosis and impaired epithelial barrier function play a key role in inflammatory bowel disease (IBD). Tofacitinib citrate, a Janus kinase (JAK) inhibitor approved for IBD, modulates immune responses via the JAK-STAT (Janus kinase–signal transducer and activator of transcription) pathway, yet its effects on the gut microbiome remain unclear. Here, we employed the short-term colon model (ProDigest, BE) containing human microbiota from three Crohn’s Disease donors to assess fermentative and metabolic activities and microbial composition following 48 h of tofacitinib treatment. A Caco-2/THP1 co-culture system was used to assess the impact of tofacitinib on epithelial immunomodulation and barrier integrity. Tofacitinib did not significantly affect microbiota composition and fermentative or metabolic activity. However, it consistently reduced pro-inflammatory chemokines motif chemokine ligand 10 (CXCL10) and monocyte chemoattractant protein-1 (MCP-1), and interleukin-6 (IL-6) in specific donors, indicating targeted immunomodulatory effects. These findings suggest that while tofacitinib may have a minimal impact on microbiota function, it may exert anti-inflammatory effects via microbiota-derived metabolites. The short-term colon model represents a robust platform for investigating microbiome-drug interactions relevant to IBD.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"216 ","pages":"Article 107365"},"PeriodicalIF":4.7,"publicationDate":"2025-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145476864","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting neuroinflammation in Parkinson's Disease: Immunomodulatory effects of a Hyaluronic Acid-Based Nanoreinforced Hydrogel Loaded with GDNF and Mesenchymal Stem cells.","authors":"Rubén Del Campo-Montoya, Xavier Mulet I Piera, Silvia Romero-Murillo, Enrique Santamaría, Elisa Garbayo, María J Blanco-Prieto","doi":"10.1016/j.ejps.2025.107368","DOIUrl":"https://doi.org/10.1016/j.ejps.2025.107368","url":null,"abstract":"<p><p>Like other neurodegenerative disorders, Parkinson's disease is marked by widespread neuroinflammation, which may contribute to its etiology and is a key component of its progression. Consequently, anti-inflammatory strategies, which can incorporate regenerative and cell therapy components, are promising therapeutic candidates for the management of the disease. To this end, we have developed a supramolecular hydrogel (HG) based on modified hyaluronic acid that combines nanoencapsulated GDNF (NPs GDNF), a potent neurotrophic factor with a less well-studied anti-inflammatory potential, and human mesenchymal stem cells (MSCs). We have evaluated the anti-inflammatory effect of the HG by quantifying the NO produced by a murine microglia cell line against LPS. In addition, we have corroborated these functional results by transcriptomic analyses, where we have also been able to delve deeper into the mechanisms by which the HG exerts this anti-inflammatory effect. We have observed that both HG components (GDNF and MSCs) and the combination of all of them (HG-NPs GDNF-MSCs) are able to decrease NO production in microglia insulted with LPS. Furthermore, we have been able to corroborate these results at the transcriptional level, where HG was able to decrease most of the pathways commonly associated with inflammation, such as interferon regulators or the interleukins IL-1 or TNF-α. In conclusion, the developed HG was able to reduce inflammation in a murine microglial cell line, both transcriptionally, with the suppression of pro-inflammatory pathways, and functionally, with a reduction in nitric oxide production.</p>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":" ","pages":"107368"},"PeriodicalIF":4.7,"publicationDate":"2025-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145476936","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Passive microfluidic-based core-shell drug delivery: a fluid mechanics-centric review","authors":"Yasaman Mozhdehbakhsh Mofrad ,&nbsp;Sasan Asiaei","doi":"10.1016/j.ejps.2025.107366","DOIUrl":"10.1016/j.ejps.2025.107366","url":null,"abstract":"<div><div>Core-shell microparticles have gained significant attention in drug delivery systems due to their ability to encapsulate multiple compounds, provide controlled release, and enhance stability. Conventional synthesis methods often face challenges in achieving uniform particle size and shell thickness. This review summarizes passive microfluidic techniques as a precise and reproducible approach for producing core-shell microparticles. The review focuses on the microfluidic aspects of the process, with three key parameters analyzed: physical properties of the phases, flow characteristics, and microfluidic chip geometries. Previous studies on the effects of hydrodynamic parameters (including flow rate, viscosity, and interfacial tension) on droplet formation are summarized, along with analyses of how different microfluidic chip geometries optimize particle size and morphology. By compiling and analyzing data from previous studies, this review provides a comprehensive analytical framework that can aid in optimizing process parameters for generating monodisperse droplets with precise control over shell thickness and core size. This extensive review highlights the key factors influencing passive core-shell microparticle production and offers guidance for designing and developing more efficient microfluidic systems for drug delivery and other biomedical applications.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"216 ","pages":"Article 107366"},"PeriodicalIF":4.7,"publicationDate":"2025-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145476787","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Application of artificial neural network to determine optimum formulation development and in vitro characterization of methylene blue and galantamine loaded polymeric nanoparticles for the treatment of Alzheimer’s disease","authors":"Busra Ozturk ,&nbsp;Huriye Demir ,&nbsp;Mine Silindir-Gunay ,&nbsp;Yagmur Akdag ,&nbsp;Selma Sahin ,&nbsp;Tugba Gulsun","doi":"10.1016/j.ejps.2025.107364","DOIUrl":"10.1016/j.ejps.2025.107364","url":null,"abstract":"<div><div>Alzheimer's disease is a major neurodegenerative disorder characterized by complex pathophysiology and currently lacks a curative treatment. This study aims to develop and characterize methylene blue and galantamine co-loaded PLGA nanoparticles, surface-modified with poloxamer 188 and GSH, to increase blood residence time and improve brain-targeted delivery. The nanoparticles were prepared using the double emulsion solvent evaporation method, and their physicochemical properties were characterized by TEM, FT-IR, DSC, XRD, and ¹³C NMR. Artificial neural network modeling was used to optimize the formulation parameters, including PLGA %, PVA %, and sonication time, for predicting particle size and encapsulation efficiencies of methylene blue and galantamine. Results showed that the optimized nanoparticles had particle sizes &lt;200 nm, appropriate zeta potential, and high encapsulation efficiencies. DSC, FT-IR, XRD, and NMR analyses confirmed the absence of crystalline peaks for methylene blue and galantamine, indicating successful encapsulation. Artificial neural network models demonstrated high predictive accuracy, serving as a valuable tool for formulation optimization. This dual-drug, surface-modified nanoparticle approach offers promising potential for multi-target therapy in Alzheimer's disease.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"216 ","pages":"Article 107364"},"PeriodicalIF":4.7,"publicationDate":"2025-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145458028","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessment of pulmonary delivery efficacy of archaeal tetraether lipids based ICG- and DiR-loaded liposomes for antitumoral photodynamic therapy","authors":"Rashid Munir ,&nbsp;Lisa Schöne ,&nbsp;Aman Ullah,&nbsp;Konrad Engelhardt,&nbsp;Eduard Preis,&nbsp;Jens Schäfer,&nbsp;Muhammad Umair Amin,&nbsp;David Schorr,&nbsp;Ibrahim Awak,&nbsp;Anam Sajjad Khan,&nbsp;Ayesha Ishfaq,&nbsp;Raneem Ahmad,&nbsp;Udo Bakowsky","doi":"10.1016/j.ejps.2025.107362","DOIUrl":"10.1016/j.ejps.2025.107362","url":null,"abstract":"<div><div>Lung cancer remains a leading cause of cancer-related deaths worldwide, highlighting the urgent need for novel therapeutic strategies, whereby pulmonary delivery offers a more promising approach, as it delivers the therapeutic moiety directly to the lungs, reducing systemic toxicity. Among emerging novel treatment strategies, photodynamic therapy (PDT) has emerged as a minimally invasive approach for treating various diseases, including lung cancer. However, the practical application of photosensitizers remains challenging due to their poor stability and limited availability at the targeted site. In this study, archaeal tetraether lipid (TEL)-based liposomes were developed to encapsulate indocyanine green (ICG) and 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindotricarbocyanine iodide (DiR), two near-infrared (NIR) fluorescent photosensitizers, for inhalable, lung-targeted PDT. Liposomes were prepared using the thin-film hydration method with a lipid composition of 1,2-dipalmitoyl-sn‑glycero-3-phosphocholine (DPPC), cholesterol (Chol), and hydrolyzed glycerol dialkyl nonitol tetraether (hGDNT) in a molar ratio of 85:10:5 and DPPC, Chol, and polar lipid fraction E (PLFE) in a molar ratio of 85:10:5. Physicochemical characterization demonstrated that both hGDNT- and PLFE-based liposomes were in the nanometer size range with good monodispersity. Compared to hGDNT-liposomes, PLFE-based formulations were generally smaller, more uniform, and exhibited greater surface charge stability. All formulations exhibited excellent colloidal stability for up to two weeks (14 days), maintaining their physicochemical characteristics both during storage and after aerosolization using a vibrating-mesh nebulizer. A spherical nanoscale morphology was revealed by atomic force microscopy (AFM). Alterations in membrane properties induced by the incorporation of the drug were highlighted by phase imaging, confirming successful encapsulation and structural modulation, whereas transmission electron microscopy (TEM) revealed the unilamellarity of the liposomal formulations. PDT assessment on A549 cells revealed that DiR-loaded hGDNT-lipsomes (DiR-hGDNT-LPs) exhibited greater phototoxicity with a 50 % inhibitory concentration (IC₅₀) of 9.65 µg/mL, compared to 16.45 µg/mL for ICG-loaded-hGDNT-liposomes (ICG-hGDNT-LPs) upon NIR irradiation. Confocal laser scanning microscopy analysis demonstrated that DiR-hGDNT-LPs and ICG-hGDNT-LPs were efficiently taken up by A549 cells, with fluorescence predominantly localized in the cytoplasm, indicating effective intracellular retention. Intracellular reactive oxygen species (ROS) generation was confirmed using the 2′,7′-dichlorofluorescin diacetate assay, which exhibited strong light-dependent ROS production upon NIR radiation. These results suggest that TEL liposomes are highly stable, efficient nanocarriers that enhance the therapeutic potential of photosensitizers for non-invasive lung-targeted PDT.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"216 ","pages":"Article 107362"},"PeriodicalIF":4.7,"publicationDate":"2025-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145451292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Design and optimisation of phospholipid vesicles for topical betamethasone dipropionate","authors":"Luca Casula ,&nbsp;Mercedes Vitek ,&nbsp;Alenka Zvonar Pobirk ,&nbsp;Mirjam Gosenca Matjaž ,&nbsp;Donatella Valenti ,&nbsp;Aurélien Dupont ,&nbsp;Carla Caddeo","doi":"10.1016/j.ejps.2025.107363","DOIUrl":"10.1016/j.ejps.2025.107363","url":null,"abstract":"<div><div>Betamethasone dipropionate is a topical corticosteroid widely used to treat common dermatoses and skin disorders. However, the poor skin penetration of traditional betamethasone dipropionate formulations can impair therapeutic outcomes. In the present study, betamethasone dipropionate was formulated in phospholipid vesicles to maximise its benefits and minimise its side effects. Liposomes and transfersomes were developed using the direct sonication method and thoroughly characterised by light scattering, cryo-transmission electron microscopy (TEM), small-angle x-ray scattering (SAXS), rheological analysis and skin permeation studies. Human skin epithelial-like cells were used to study how the phospholipid vesicles affected cell proliferation and morphology. Both the liposomes and transfersomes were nanosized, spherical and predominantly unilamellar, but the transfersomes were smaller, more homogeneous and stable on storage due to the presence of Tween<strong>®</strong> 80. The latter was also responsible for a higher viscosity, which decreased at 32 °C, the temperature of the skin surface, as determined by rheological analysis. Furthermore, tests of the formulations in skin cells showed the absence of cytotoxicity and increased skin permeation. Phospholipid vesicles represent a promising approach for betamethasone dipropionate delivery, as they are characterised by high stability and cytocompatibility. These properties may improve the therapeutic outcomes and minimise the side effects of betamethasone dipropionate, encouraging further investigation to confirm the effective and safe use of betamethasone dipropionate nanoformulations on the skin.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"216 ","pages":"Article 107363"},"PeriodicalIF":4.7,"publicationDate":"2025-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145458068","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pulmonary delivery of anti-infectives from natural sources: Development and characterization of liposomal sanggenon formulations","authors":"Jacqueline Schwarzinger ,&nbsp;Gianluca Bello ,&nbsp;Timur Tropin ,&nbsp;Christian Wölk ,&nbsp;Clement Blanchet ,&nbsp;Sigrid Adelsberger ,&nbsp;Gabriela Hädrich ,&nbsp;Judith M. Rollinger ,&nbsp;Ulrike Grienke ,&nbsp;Richard D. Harvey ,&nbsp;Lea Ann Dailey","doi":"10.1016/j.ejps.2025.107361","DOIUrl":"10.1016/j.ejps.2025.107361","url":null,"abstract":"<div><div>Sanggenon C (SGC) and sanggenon D (SGD) are stereoisomeric natural products with promising anti-infective potential, especially against pathogens involved in acute respiratory infections. However, their bulky structures, poor aqueous solubility, and low oral bioavailability present major therapeutic challenges. Inhalation enables direct delivery to the site of infection while minimizing systemic exposure. Liposomal formulations DMPC:DMPG (2:1 w/w) of SGC and SGD, prepared via ethanol injection, achieved high drug loadings (&gt; 3.5 mg/mL). Drug-lipid interactions were evaluated via DSC, Langmuir trough studies, SAXS, and cryo-TEM, showing incorporation of the compounds in the lipid bilayer. While stereochemistry-dependent differences were evident in vesicle size and thermotropic behavior, other biophysical data indicated that these differences were largely mitigated upon formulation. Liposomal formulations showed an excellent stability during nebulization with a vibrating mesh nebulizer (mass median aerodynamic diameters: 1.30–1.35 µm) and the high affinity of the compounds for the lipid bilayer resulted in a sustained in vitro release profile (8–9 % after 240 h). The retention of the drugs in the liposomes also significantly reduced cytotoxicity at 24 h compared to neat compounds. These findings highlight the importance of stereochemistry in drug-membrane interaction, yet their similar formulation performance suggests that both compound formulations are promising candidates for pulmonary anti-infective therapy.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"215 ","pages":"Article 107361"},"PeriodicalIF":4.7,"publicationDate":"2025-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145451274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unexpected effects of antibiotics on microbiota-mediated drug metabolism in a fistulated dog model","authors":"Tiago Sousa ,&nbsp;Charlotte Yeung ,&nbsp;Conor Beaupres De Monsales ,&nbsp;Nannapat Sangfuang ,&nbsp;Anders Borde ,&nbsp;Bertil Abrahamsson ,&nbsp;Abdul W. Basit","doi":"10.1016/j.ejps.2025.107360","DOIUrl":"10.1016/j.ejps.2025.107360","url":null,"abstract":"<div><div>The human gut microbiome plays a crucial role in the metabolism of drugs, with various bacterial species catalysing the biotransformation of pharmaceutical compounds. <em>In vitro</em> microbiota models, typically derived from faecal material, have been employed to study this phenomenon. However, they often do not fully capture the complex and dynamic environment of the living colon. This study aimed to evaluate whether <em>in vitro</em> models accurately reflect <em>in vivo</em> microbiota-drug interactions by comparing both approaches within the same individual animal via a fistulated dog model, with the fistula located in the ascending colon. We investigated the metabolism of metronidazole and sulindac, two structurally and pharmacologically distinct drugs, before and after broad-spectrum antibiotic treatment. Prior to antibiotics, <em>in vitro</em> biotransformation in faecal material was observed for both drugs: metronidazole (t₁/₂ = 22.9 ± 1.2 min) and sulindac (t₁/₂ = 104.2 ± 1.0 min). Following antibiotic treatment, no measurable degradation occurred <em>in vitro</em>. However, in the fistulated dog model plasma concentrations decreased following antibiotic treatment compared to pre-treatment levels, indicating a lack of correlation between microbiota metabolism observed <em>in vitro</em> and systemic drug levels <em>in vivo</em>. These findings underscore the complexity of microbiota-host-drug interactions and provide important insights for the development of translational microbiome–pharmacology models. Additionally, the drawbacks over the use of antibiotic-treated animal models to study microbiota-drug interactions are discussed due to antibiotic-induced changes in intestinal permeability and efflux that may influence drug absorption and metabolism.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"216 ","pages":"Article 107360"},"PeriodicalIF":4.7,"publicationDate":"2025-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145444417","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Implantable drug delivery system improves tolerability of anti-CD40/anti-PD1 and chemotherapy in a murine model of breast cancer","authors":"Samantha J. Wade ,&nbsp;Elahe Minaei ,&nbsp;Ashleigh Hope ,&nbsp;Ross J Turner ,&nbsp;Chelsea Penney ,&nbsp;Paul A. Beavis ,&nbsp;Junyun Lai ,&nbsp;Gordon G. Wallace ,&nbsp;Sameera Ansar ,&nbsp;Naila Islam ,&nbsp;Alistair Lochhead ,&nbsp;Daniel Brungs ,&nbsp;Morteza Aghmesheh ,&nbsp;Kara L. Vine-Perrow","doi":"10.1016/j.ejps.2025.107359","DOIUrl":"10.1016/j.ejps.2025.107359","url":null,"abstract":"<div><div>Triple negative breast cancer (TNBC) is associated with the poorest prognosis among breast cancer subtypes and while immunotherapy has demonstrated some promise, its effectiveness as a monotherapy remains limited, offering only modest improvements in clinical outcomes when combined with chemotherapy. Immune checkpoint therapies, such as PD-1 inhibitors, elicit responses in a subset of patients with metastatic TNBC, and few patients experience durable effects. One reason for this limited efficacy may be due to defects in antigen presentation, as the deficiency of dendritic cells, essential for effective antigen presentation, correlates with inadequate anti-tumour immunity. To address this challenge, we report the development of a novel implantable drug delivery device that enables the localized administration of a CD40 agonist in combination with anti-PD1, doxorubicin and nanoparticle albumin–bound paclitaxel (nab-paclitaxel). CD40 agonists are a unique class of agents that activate antigen-presenting cells, including dendritic cells and B cells, and reprogram macrophages to support anti-tumour immunity. By enabling targeted delivery to the tumour site, we aimed to enhance immune priming while mitigating systemic toxicities often observed with combinations of intravenous chemo-immunotherapy. In a 4T1 murine model of TNBC, repeated systemic administration of the therapeutic combination led to fatal xenogeneic reactions, which were not observed with the localized delivery approach. Localized delivery also slowed tumour growth compared to systemic administration of the therapeutic compounds. Immune profiling further revealed that the addition of anti-CD40 agonist antibody promoted the activation of PD-1+ CD8+ <em>T</em> lymphocytes within the lymph nodes in both locally and systemically treated animals. However, the localized approach achieved equivalent or enhanced immune activation without inducing the fatal immune reactions observed with systemic dosing, suggesting that localized treatment can offer a significant therapeutic advantage. This study demonstrates that our innovative localized delivery approach has the potential to significantly improve patient outcomes by maximizing efficacy and minimizing adverse effects for this aggressive subtype of breast cancer.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"216 ","pages":"Article 107359"},"PeriodicalIF":4.7,"publicationDate":"2025-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145444463","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of anti-drug antibodies against therapeutic monoclonal antibodies and related product in Japanese patients with rheumatoid arthritis and their clinical impact","authors":"Hiroko Shibata ,&nbsp;Kazuko Nishimura ,&nbsp;Eri Tsukagoshi ,&nbsp;Akiko Ishii-Watabe ,&nbsp;Yoshiro Saito ,&nbsp;Soichi Yamada ,&nbsp;Shotaro Masuoka ,&nbsp;Wataru Hirose ,&nbsp;Shinichi Kawai ,&nbsp;Toshihiro Nanki","doi":"10.1016/j.ejps.2025.107357","DOIUrl":"10.1016/j.ejps.2025.107357","url":null,"abstract":"<div><div>Biopharmaceuticals are widely used to treat rheumatoid arthritis (RA) due to their high therapeutic efficacy. However, these drugs may elicit immunogenicity and induce the production of anti-drug antibodies (ADA), potentially impacting their efficacy and safety. Therefore, the detection and characterization of ADA in patient samples during clinical development is crucial. However, data regarding biopharmaceutical immunogenicity and associated clinical factors in Japanese patients with RA remain limited. Here, we measured ADA levels in the sera of Japanese patients with RA treated with biopharmaceuticals (infliximab, adalimumab, golimumab, tocilizumab, and etanercept), investigated the clinical factors associated with ADA formation, and examined the effect of ADA on the pharmacological activity of each drug. Although the prevalence of ADA varied among biopharmaceuticals, no apparent neutralizing activity was observed. Among clinical factors, the use of concomitant methotrexate (MTX) influenced ADA prevalence in patients treated with adalimumab and the route of administration was a significant factor in patients treated with tocilizumab. Analyzing the relationship between ADA-positive/negative status and human leukocyte antigen (HLA) revealed that <em>HLA-DRB1</em>*<em>04:01</em> allele frequency tended to be higher in the anti-etanercept ADA-positive group. The free drug concentration tended to be lower in ADA-positive samples, suggesting that the presence of ADA may have pharmacokinetic implications. Although experimental evaluation of the impact of ADA on drug pharmacological activity in patient samples is typically complex, we developed a method to measure residual drug bioactivity using cell-based assays as an alternative to evaluating the neutralization activity of ADA, and demonstrated the utility of this approach to assess the clinical impact of ADA.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"216 ","pages":"Article 107357"},"PeriodicalIF":4.7,"publicationDate":"2025-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145430636","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}