European Journal of Pharmaceutical Sciences最新文献

{"title":"Biosimilars and interchangeability: Regulatory, scientific, and global perspectives","authors":"Alper Bektas Iskit","doi":"10.1016/j.ejps.2025.107224","DOIUrl":"10.1016/j.ejps.2025.107224","url":null,"abstract":"<div><div>Biological medicines, biologics have transformed the treatment of many serious diseases but are often costly. As patents expire on original biologics, biosimilars have emerged to improve access. A biosimilar is generally defined as a biologic product that is highly similar to an already authorized biologic,the reference product, with no clinically meaningful differences in safety, purity, or efficacy. Because biologics are made in living systems and naturally variable, a biosimilar cannot be an exact copy of its reference; instead, it is developed through a rigorous comparability process to ensure it matches the reference product’s critical attributes within an acceptable range. If successful, biosimilar should perform just as safely and effectively in patients as the original product. This article reviews the scientific basis of biosimilars and the concept of interchangeability, global regulatory frameworks (EMA, FDA, WHO), key requirements for analytical comparability, pharmacokinetic/pharmacodynamic studies, immunogenicity assessment, criteria for interchangeability (including switching studies and post-approval surveillance), and real-world evidence on the safety of biosimilar substitution. Relevant regulatory guidelines and recent literature are cited throughout to provide an up-to-date, scholarly overview.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"213 ","pages":"Article 107224"},"PeriodicalIF":4.7,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144783855","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":"Engineered carbon dots for mucosal gene delivery","authors":"Samuel Arca,&nbsp;Françoise Pons,&nbsp;Luc Lebeau","doi":"10.1016/j.ejps.2025.107222","DOIUrl":"10.1016/j.ejps.2025.107222","url":null,"abstract":"<div><div>Although lung gene therapy holds promise for treating various life-threatening lung diseases, its efficacy is hindered by the mucus layer covering the airways, whose role is to protect the lung epithelium from airborne threats. For efficient gene delivery to the epithelial cells, it is necessary to ensure rapid passage of the transfection particles through the mucus layer before they are eliminated by mucociliary clearance. We developed mucus-penetrating gene carriers using carbon dots (CDs) synthesized from citric acid and bPEI600. Various strategies were investigated to convert these CDs into muco-inert nanoparticles, including PEGylation and decoration with zwitterionic or mucolytic species. After thorough characterization, we assessed their interactions with a mucus model through turbidimetry and transport measurements, as well as their effects on mucus rheology. The efficacy of the carriers to deliver DNA to various cell models was established. Particularly, Calu-3 cells, cultured at the air-liquid interface to obtain abundant mucus production, were used as a discriminating model to evaluate the potency of CDs to deliver their DNA cargo through mucus. While zwitterion-coated CDs failed to induce significant transgene expression, those with PEG decorations yielded moderate results, and CDs designed as thiol reservoirs for local mucolytic action achieved high transfection rates.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"213 ","pages":"Article 107222"},"PeriodicalIF":4.7,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144764713","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":"Photodynamic drug delivery for cancer therapy: Designing liposomes for light-controlled release and enhanced drug efficacy","authors":"Tristan Le Clainche ,&nbsp;Ahmed Gamal Ali Abdelhamid ,&nbsp;Nazareth Milagros Carigga Gutierrez ,&nbsp;Marie-Anne Jourdain ,&nbsp;Sofia Leo ,&nbsp;Lucie Sancey ,&nbsp;Amandine Hurbin ,&nbsp;Jean-Luc Coll ,&nbsp;Bénédicte Elena-Herrmann ,&nbsp;Mans Broekgaarden","doi":"10.1016/j.ejps.2025.107221","DOIUrl":"10.1016/j.ejps.2025.107221","url":null,"abstract":"<div><div>Photodynamics involves the use of photocatalytic compounds that, upon excitation with light, produce reactive oxygen species and have seen widespread applications in the treatment of cancer in the form of photodynamic therapy. Within the field of drug delivery, photodynamics has emerged as a strikingly effective approach for spatiotemporal-controlled drug release by harnessing photochemical redox reactions to destabilize lipid nanoformulations that contain oxidation-susceptible excipients. Despite highly promising outcomes in preclinical models, such controlled release modalities have not yet been explored in clinical cancer trials. This review outlines key design considerations for lipid nanoformulations in photodynamic drug delivery, focusing on their susceptibility to photochemical redox reactions, their ability to induce lysosomal permeabilization, and facilitate microenvironmental priming that enhances tumor permeability. These considerations first highlight the role of specific lipid excipients in determining photodynamic drug release efficiencies. Secondly, the selection of the photosensitizing agents is considered, which ideally absorb light &gt;650 nm and exhibit limited leaching. Thirdly, the selected photosensitizing agent and pharmaceutical cargoes may dictate which drug loading approach should be pursued, and how drug release is detected. We particularly highlight the promise of nuclear magnetic resonance (NMR) spectroscopy as it can provide non-destructive quantification of encapsulated and released pharmaceutical cargoes, alongside structural assessments of the lipid nanoformulations, without the need for prior separation or complex sample preparation. Finally, considering the corollary effects of photodynamics on cancer cells and the cancer microenvironment, we emphasize the utility of a multi-model approach to evaluate novel photodynamic drug delivery systems. By providing these design considerations, this review aims to boost the field of photodynamic drug delivery and encourage its exploitation in translational cancer research. Moreover, these aspects are equally relevant to stimulate investigations towards oxidation-responsive drug release triggered by alternative external stimuli, thereby broadening the drug delivery arsenal against cancer.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"213 ","pages":"Article 107221"},"PeriodicalIF":4.7,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144764715","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":"Retraction notice to “Porphyrins to restrict progression of pancreatic cancer by stabilizing KRAS G-quadruplex: In silico, in vitro and in vivo validation of anticancer strategy” [European Journal of Pharmaceutical Sciences 125 (2018) Pages 39-53]","authors":"Rudradip Pattanayak ,&nbsp;Atish Barua ,&nbsp;Amlan Das ,&nbsp;Tanima Chatterjee ,&nbsp;Adrija Pathak ,&nbsp;Pritha Choudhury ,&nbsp;Srikanta Sen ,&nbsp;Prosenjit Saha ,&nbsp;Maitree Bhattacharyya","doi":"10.1016/j.ejps.2025.107196","DOIUrl":"10.1016/j.ejps.2025.107196","url":null,"abstract":"","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"212 ","pages":"Article 107196"},"PeriodicalIF":4.7,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144752778","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":"Intelligent drug codelivery platform for immune microenvironment reconstruction and immunochemotherapy in osteosarcoma treatment","authors":"Yi Zhang ,&nbsp;Yuxuan Wu ,&nbsp;Yuanzhuo Xie,&nbsp;Guojing Liu,&nbsp;Shoufeng Wang","doi":"10.1016/j.ejps.2025.107218","DOIUrl":"10.1016/j.ejps.2025.107218","url":null,"abstract":"<div><div>Immunotherapy has emerged as a new strategy for tumor suppression, but its effectiveness is restricted by the immunosuppressive tumor microenvironment (TME) in the context of osteosarcoma treatment. Therefore, a series of therapies focused on immune activation have been introduced as combination treatments with immunotherapy, especially chemotherapies with the ability to induce immunogenic cell death (ICD). In this study, we designed a nanosized platform (^CCHANP_DOX) to codeliver doxorubicin (DOX) and cisplatin (CDDP) to the tumor site for synergistic killing of malignant cells. Due to the ability of DOX to induce ICD, the immunogenicity of the TME was reconstructed <em>via</em> tumor-specific antigen exposure and dendritic cell maturation. Furthermore, ^CCHANP_DOX treatment increased the sensitivity of tumors to anti-programmed cell death-1 (aPD-1). Our in vivo results demonstrated that the combination of ^CCHANP_DOX and aPD-1 not only successfully depressed tumor growth but also inhibited tumor recurrence and lung metastasis. The enhanced anti-tumor effect can be attributed to the activated immune response and established immune memory. This combination may be a potential immunochemotherapy option for osteosarcoma.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"212 ","pages":"Article 107218"},"PeriodicalIF":4.7,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144750403","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":"Retraction notice to “Electrospun gold nanorods/graphene oxide loaded-core-shell nanofibers for local delivery of paclitaxel against lung cancer during photo-chemotherapy method” [European Journal of Pharmaceutical Sciences 164 (2021) 105914]","authors":"Mohammadreza Hasani Azerbaijan ,&nbsp;Ehsan Bahmani ,&nbsp;Mania Habibi Jouybari ,&nbsp;Amir Hassaniazardaryani ,&nbsp;Pouya Goleij ,&nbsp;Mohammad Akrami ,&nbsp;Mohammad Irani","doi":"10.1016/j.ejps.2025.107197","DOIUrl":"10.1016/j.ejps.2025.107197","url":null,"abstract":"","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"212 ","pages":"Article 107197"},"PeriodicalIF":4.7,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144741727","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":"Selection of locally administered ocular tissue-targeting RNA aptamers using in vivo SELEX","authors":"Katja Stenberg ,&nbsp;Sonja Korhonen ,&nbsp;Umair Seemab ,&nbsp;Daniel Miotto Dupont ,&nbsp;Jørgen Kjems ,&nbsp;Paavo Honkakoski ,&nbsp;Astrid Subrizi","doi":"10.1016/j.ejps.2025.107217","DOIUrl":"10.1016/j.ejps.2025.107217","url":null,"abstract":"<div><div>The number of patients affected by retinal diseases is increasing worldwide, and more effective ocular drug delivery strategies are needed. Intravitreal anti-VEGF therapy has reduced the rates of visual impairment and blindness; however, frequent injections cause a significant burden on patients, resulting in poor compliance and therapeutic outcome. Thus, a targeted approach with less invasive administration could extend the dosing intervals and offer a patient-friendly alternative to the current standard of intravitreal injection. Here, <em>in vivo</em> Systematic Evolution of Ligands by Exponential Enrichment (SELEX) was conducted to select ocular tissue-targeting aptamers in rat using topical eye drops and subconjunctival injection. Data analysis of the sequenced aptamer pools revealed significant enrichment of Apt2 and Apt4 in ocular tissues. Their <em>in vivo</em> biodistribution was further evaluated using quantitative real-time PCR (qRT-PCR) at 0.5, 7, and 24 h after subconjunctival administration. Both aptamers accumulated preferentially in posterior ocular tissues, with Apt2 levels exceeding those of the control aptamer by a factor of two at 0.5 h and four at 24 h. This study demonstrates that <em>in vivo</em> SELEX is a viable tool to select ocular tissue-targeting aptamers from the ocular surface. This method could be utilized in the discovery of ocular targeting aptamers for therapeutic purposes and help uncover novel drug targets for various ocular disorders.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"212 ","pages":"Article 107217"},"PeriodicalIF":4.7,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144741728","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":"From hypothesis to forecasting: The impact of within-subject variability of gastro-intestinal physiology in relation to likelihood of sex-dependent outcome of bioequivalence","authors":"Vijith Roy Titus ,&nbsp;Maitri Sanghavi ,&nbsp;Masoud Jamei ,&nbsp;Amin Rostami-Hodjegan","doi":"10.1016/j.ejps.2025.107213","DOIUrl":"10.1016/j.ejps.2025.107213","url":null,"abstract":"<div><div>There are calls for inclusion of both sexes when conducting bioequivalence (BE) studies as this is not common practice for variety of reasons. There are not many proven cases for sex-dependent outcome of BE studies; hence inclusion of female participants in BE studies is considered as a matter of equity and principle. Most typical BE studies are cross-over design where between-subject variability (including sex effects) plays no role. However, within-subject variability (WSV) can still play a significant role, in passing the BE criteria.</div><div>It has been shown that WSV of gastrointestinal (GI) tract as well as drug disposition factors propagate to the pharmacokinetics, defining the outcome of BE. By applying known sex-based differences in WSV measures of colonic transit time (CTT) and gastric emptying time (GET), we illustrate how hypotheses can be formulated regarding potential sex-dependent outcomes in BE studies. This approach supports informed decision-making on the necessity of including female participants or justifying prudent waivers for their inclusion.</div><div>Virtual Bioequivalence (VBE) assessments were carried out (using VBE module in Simcyp V22 (Certara Predictive Technologies, Sheffield, UK)) where three hypothetical drugs product with distinct dissolution rates were evaluated against multiple virtual test formulation counterparts. The influence of sex-dependent WSV in CTT and GET on VBE outcomes was demonstrated by systematic analysis of discordance between BE in female vs. male subjects. The exercise provided a roadmap for generating hypotheses regarding the propagation of sex differences in physiology to BE outcome.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"212 ","pages":"Article 107213"},"PeriodicalIF":4.7,"publicationDate":"2025-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144729004","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":"Microfluidic-assisted synthesis of integrin-targeting cRGD liposomes as a scalable strategy for theranostic applications in triple-negative breast cancer","authors":"Karina Ovejero-Paredes ,&nbsp;Giovanni Bisbano ,&nbsp;Inge Flier ,&nbsp;Alejandro González-Simón ,&nbsp;Marzia Marciello ,&nbsp;Sabrina Oliveira ,&nbsp;Marco Zupi ,&nbsp;Davide Rubes ,&nbsp;Fatima Ayash ,&nbsp;Filippo Doria ,&nbsp;Valentina Pirota ,&nbsp;Marco Terreni ,&nbsp;Massimo Serra ,&nbsp;Marco Filice","doi":"10.1016/j.ejps.2025.107216","DOIUrl":"10.1016/j.ejps.2025.107216","url":null,"abstract":"<div><div>Triple negative breast cancer (TNBC) represents one of the most aggressive types of cancer, with a difficult treatment leading to poor prognosis of the disease. Herein we report the synthesis of a custom-made cyclic RGD peptide (cRGD), and its use in decorating liposomes for targeted drug delivery of doxorubicin to TNBC cells overexpressing integrin receptor α_vβ₃. Liposomes carrying dibenzocyclooctine groups on their surface were produced using an optimized large scale microfluidic-assisted approach and subsequently conjugated with cRGD bearing an acyl azide group by means of a click chemistry reaction. This functionalization promotes enhanced cellular uptake via integrin-mediated endocytosis. <em>In vitro</em> assessments confirm enhanced selectivity and cytotoxicity of cRGD-liposomes against triple-negative cancer cells, in addition to dual imaging capabilities by fluorescence and magnetic resonance techniques due to the incorporation of a fluorescent dye and gadolinium complex, respectively. These features support the potential of cRGD-liposomes as a promising platform for targeted drug delivery to specific cancer cell populations, establishing them as viable theranostic agents for precision medicine applications.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"213 ","pages":"Article 107216"},"PeriodicalIF":4.7,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144717757","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":"Integrating transcriptomics, network analysis, and single-cell RNA sequencing to identify and validate key target genes of gynostemma in the treatment of non-alcoholic fatty liver disease","authors":"Xiao Li ,&nbsp;Huifang Lai ,&nbsp;Xiaoping Wang","doi":"10.1016/j.ejps.2025.107214","DOIUrl":"10.1016/j.ejps.2025.107214","url":null,"abstract":"<div><div>This study explores the therapeutic targets and mechanisms of Gynostemma pentaphyllum in non-alcoholic fatty liver disease (NAFLD). Using network analysis and bioinformatics, we identified target genes of Gynostemma’s active metabolites in NAFLD through differential expression analysis, Weighted Gene Co-expression Network Analysis (WGCNA), and machine learning algorithms. From the intersection of 2,569 differentially expressed genes (DEGs), 1,279 key modular genes, and 532 target genes, 19 intersecting target genes were pinpointed, with PIM1, TYMS, and SLC29A1 identified as key targets. PIM1 was downregulated in NAFLD samples, while TYMS and SLC29A1 were upregulated. A nomogram based on these genes showed strong diagnostic potential for NAFLD. These genes were enriched in pathways related to spliceosome, lysosome, and purine metabolism. High infiltration levels of activated CD8 T cells, CD56bright natural killer cells, gamma delta T cells, and immature B cells were observed in NAFLD samples, negatively correlated with PIM1 and positively correlated with TYMS and SLC29A1. Single-cell analysis revealed higher PIM1 expression within annotated immune cell clusters. RT-qPCR confirmed that Gynostemma treatment modulated these gene expressions, increasing PIM1 while decreasing TYMS and SLC29A1. In vitro, <em>Gynostemma pentaphyllum</em> reduced lipid accumulation and triglyceride levels in FFA-induced hepatic steatosis models using HepG2, HuH7, and QSG7701 cells. These findings provide scientific insights into the therapeutic mechanisms of Gynostemma in NAFLD.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"212 ","pages":"Article 107214"},"PeriodicalIF":4.7,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144706871","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}