European Journal of Pharmaceutical Sciences最新文献

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Small molecule drug absorption in inflammatory bowel disease and current implementation in physiologically- based pharmacokinetic models.
IF 4.3 3区 医学
European Journal of Pharmaceutical Sciences Pub Date : 2025-04-03 DOI: 10.1016/j.ejps.2025.107095
Jonas Langeraert, Elke Gasthuys, An Vermeulen
{"title":"Small molecule drug absorption in inflammatory bowel disease and current implementation in physiologically- based pharmacokinetic models.","authors":"Jonas Langeraert, Elke Gasthuys, An Vermeulen","doi":"10.1016/j.ejps.2025.107095","DOIUrl":"https://doi.org/10.1016/j.ejps.2025.107095","url":null,"abstract":"<p><p>Inflammatory bowel disease (IBD) is characterized by a chronic inflammation of the intestinal mucosa, with predominant localization in the colon in ulcerative colitis (UC) or affecting the entire length of the gastrointestinal tract in Crohn's disease (CD). Recent advances in the drug development space have been marked by a return to orally administered small molecules with novel mechanisms of action such as Janus kinase inhibitors. Additionally, the prevalence of certain chronic conditions is higher in IBD patients, many of which are treated with orally administered drugs. Given the pathophysiology and localization of IBD, altered drug absorption from the gastrointestinal tract can be expected. This review discusses several physiological differences between the small and large intestine with the potential to influence drug absorption including pathophysiology related alterations associated with IBD. The main physiological parameters which are identified include luminal fluid volume, luminal pH, transit time, bile salt concentration, microbiome, absorptive surface area, permeability and metabolizing enzymes and transporters. Literature regarding these factors in IBD patients is marked with high heterogeneity in reporting of disease severity and location leading to difficulties in interpreting data across different studies. While the influence of most of these factors has been directly assessed in healthy volunteers, this is rarely the case for IBD patients. Furthermore, studies which used PBPK modelling to describe the PK of an orally administered drug in an IBD population and were able to verify their findings using clinical data are critically examined. These models were able to incorporate the pathophysiological changes associated with IBD and partly succeeded in adequately predicting drug absorption in this population. Given the limited amount of PBPK studies performed on a limited number of drugs, the developed models are most likely not suitable to be used as a general PBPK model for the IBD population.</p>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":" ","pages":"107095"},"PeriodicalIF":4.3,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143788368","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}
引用次数: 0
Size dependent impact of platinum nanoparticles on doxorubicin activity
IF 4.3 3区 医学
European Journal of Pharmaceutical Sciences Pub Date : 2025-04-03 DOI: 10.1016/j.ejps.2025.107094
Patrycja Bełdzińska , Marcin Zakrzewski , Inez Mruk , Marceli Bogusławski , Natalia Derewońko , Katarzyna Bury , Dariusz Wyrzykowski , Grzegorz Gołuński , Michał Rychłowski , Jacek Piosik
{"title":"Size dependent impact of platinum nanoparticles on doxorubicin activity","authors":"Patrycja Bełdzińska ,&nbsp;Marcin Zakrzewski ,&nbsp;Inez Mruk ,&nbsp;Marceli Bogusławski ,&nbsp;Natalia Derewońko ,&nbsp;Katarzyna Bury ,&nbsp;Dariusz Wyrzykowski ,&nbsp;Grzegorz Gołuński ,&nbsp;Michał Rychłowski ,&nbsp;Jacek Piosik","doi":"10.1016/j.ejps.2025.107094","DOIUrl":"10.1016/j.ejps.2025.107094","url":null,"abstract":"<div><div>Cancer is a leading cause of death worldwide, with nearly 10 million fatalities yearly. Consequently, despite the search for new therapeutic approaches, the use of classical chemotherapy, remains one of the main treatment regimens. Therefore, we evaluate the use of platinum nanoparticles (PtNPs) of different sizes as potential modulators of doxorubicin (DOX) activity.</div><div>In the presented research, we utilized a wide range of methods, including Spectroscopic measurements, Isothermal Titration Calorimetry, Dynamic Light Scattering, and Atomic Force Microscopy, as well as biological assays such as the Ames mutagenicity test on <em>Salmonella enterica</em> serovar Typhimurium TA98 and the alamarBlue cytotoxicity assay with Fluorescent Confocal Microscopy on non-cancerous HaCaT and cancerous MelJuSo cell lines, to investigate the interactions between PtNPs and DOX and the effect of diverse-sized nanoparticles on DOX activity.</div><div>The obtained results indicate the presence of direct interactions, particularly highlighting differences related to particles size. We confirmed that DOX affects the aggregation of nanoparticles, while the nanoparticles induce DOX fluorescence quenching. In terms of biological aspects, PtNPs reduced the mutagenicity of DOX, and increased the survival of non-cancerous HaCaT cells. Furthermore, 70 nm PtNPs significantly increased DOX effects on cancerous MelJuSo cells by negatively affecting their morphology and culture density.</div><div>To conclude, our research provided valuable insights into the interactions between PtNPs and DOX with particular emphasis on the nanoparticles’ size influence highlighting nanoparticles’ impact on DOX cytotoxicity providing a base for further research on the potential future modification in treatment approaches.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"209 ","pages":"Article 107094"},"PeriodicalIF":4.3,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143785824","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}
引用次数: 0
Assessment of ventilation heterogeneity and particle deposition in asthmatics using combined SPECT/CT imaging and computational modeling approaches
IF 4.3 3区 医学
European Journal of Pharmaceutical Sciences Pub Date : 2025-04-02 DOI: 10.1016/j.ejps.2025.107093
Xuan Zhang , Prathish K. Rajaraman , Frank Li , Sanghun Choi , Alejandro P. Comellas , Eric A. Hoffman , Sean B. Fain , David W. Kaczka , Benjamin M. Smith , Jiwoong Choi , Mario Castro , Sally E. Wenzel , Nizar N. Jarjour , Mark L. Schiebler , Elliot Israel , Bruce D. Levy , John V. Fahy , Serpil C. Erzurum , Andrew Babiskin , Minori Kinjo , Ching-Long Lin
{"title":"Assessment of ventilation heterogeneity and particle deposition in asthmatics using combined SPECT/CT imaging and computational modeling approaches","authors":"Xuan Zhang ,&nbsp;Prathish K. Rajaraman ,&nbsp;Frank Li ,&nbsp;Sanghun Choi ,&nbsp;Alejandro P. Comellas ,&nbsp;Eric A. Hoffman ,&nbsp;Sean B. Fain ,&nbsp;David W. Kaczka ,&nbsp;Benjamin M. Smith ,&nbsp;Jiwoong Choi ,&nbsp;Mario Castro ,&nbsp;Sally E. Wenzel ,&nbsp;Nizar N. Jarjour ,&nbsp;Mark L. Schiebler ,&nbsp;Elliot Israel ,&nbsp;Bruce D. Levy ,&nbsp;John V. Fahy ,&nbsp;Serpil C. Erzurum ,&nbsp;Andrew Babiskin ,&nbsp;Minori Kinjo ,&nbsp;Ching-Long Lin","doi":"10.1016/j.ejps.2025.107093","DOIUrl":"10.1016/j.ejps.2025.107093","url":null,"abstract":"<div><h3>Purpose</h3><div>This study investigated asthma phenotypes and their associations with ventilation heterogeneity and particle deposition by utilizing Single-Photon Emission Computed Tomography (SPECT) imaging, quantitative Computed Tomography (qCT) imaging-based subgrouping, and a whole-lung computational model.</div></div><div><h3>Materials and methods</h3><div>Two datasets were analyzed: one from a combined SPECT and CT (SPECT/CT) study with six asthmatic subjects, and another from the Severe Asthma Research Program (SARP) with 209 asthmatic subjects. Data from 35 previously acquired healthy subjects served as a control group. Each subject underwent CT scans at full inspiration and expiration, along with pulmonary function testing (PFT). The SPECT/CT study included ventilation SPECT imaging. Key qCT variables such as airway diameter, wall thickness, percentage of air trapping (AirT%), and percentage of small airway disease (fSAD%) were assessed. A subject-specific whole-lung computational fluid and particle dynamics (CFPD) model predicted airway resistance, particle deposition fraction, and the coefficient of variation (CV) for ventilation heterogeneity. Subjects were categorized into four predefined asthma imaging subgroups/clusters with increasing severity (C1-C4). CFPD-predicted CVs were validated against SPECT measurements. We compared PFT, qCT, and CFPD variables across SARP clusters and analyzed particle deposition fractions in large conducting, small conducting, and respiratory airways.</div></div><div><h3>Results</h3><div>Cluster C4 exhibited a significantly distinct ventilation profile compared to other clusters and health controls. This distinction contrasted with the insignificant differences between ventilation profiles in severity subgroups defined by conventional spirometry-based guidelines. Airway resistance varied significantly across the asthma clusters. Although both C3 and C4 clusters represented severe asthma, only C4 showed a significant increase in AirT%, primarily due to fSAD%. Since inflammatory phenotypes differ — C3 with wall thickening in large and small conducting airways, and C4 with elevated fSAD% and Emph% in small conducting and respiratory airways — fine particles (∼5 μm) and extrafine particles (∼1 μm) are more effective at reaching the respective regions in C3 and C4. Given that C2 and C4 have hyper-responsive phenotypes with narrowed conducting airways, fine particles are more effective in reaching these areas. Airway enlargement in targeted segments of the left lower lobe resulted in improved particle deposition.</div></div><div><h3>Conclusion</h3><div>Our cluster-informed CFPD-based approach enhances the understanding of ventilation heterogeneity in asthma and holds potential for refining strategies for inhalational therapies.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"209 ","pages":"Article 107093"},"PeriodicalIF":4.3,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143783890","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}
引用次数: 0
Synthesis and physicochemical characterization of new potential haptens and their precursors with morphine skeleton
IF 4.3 3区 医学
European Journal of Pharmaceutical Sciences Pub Date : 2025-03-31 DOI: 10.1016/j.ejps.2025.107089
Balázs Simon , István Köteles , Réka Kovács , Márta Kraszni , Péter Horváth , Sándor Hosztafi , Károly Mazák
{"title":"Synthesis and physicochemical characterization of new potential haptens and their precursors with morphine skeleton","authors":"Balázs Simon ,&nbsp;István Köteles ,&nbsp;Réka Kovács ,&nbsp;Márta Kraszni ,&nbsp;Péter Horváth ,&nbsp;Sándor Hosztafi ,&nbsp;Károly Mazák","doi":"10.1016/j.ejps.2025.107089","DOIUrl":"10.1016/j.ejps.2025.107089","url":null,"abstract":"<div><div>Opiate analgetics are widely used therapeutic agents, but their side-effects can cause serious harm to users, and they are often abused for their euphoric effects. Their abuse is a serious healthcare problem worldwide, and in addition, pharmacological treatments of this disorder possess serious problems such as adverse effects, medication adherence complications, and relapse to addiction after the therapy. One possible way to combat the latter issue would be vaccination with macromolecule-opiate conjugates. Therefore, novel compounds are necessary not just as potential therapeutic agents, but also as new hapten-like molecules. In this work, we present the synthesis of novel N-cyanoalkyl- and N-aminoalkyl-noropiate derivatives, which could be used either as new therapeutic agents or haptens.</div><div>An important aim of this work was to quantify biorelevant physicochemical properties (basicity, lipophilicity) of the newly synthesized compounds. The determination of the protonation macroconstants characterizing the acid-base properties was performed by pH-potentiometry. To determine the partition coefficients, we used the shake-flask method with different octanol/water phase ratios. The complex formation of the pharmacologically active N-cyanoalkyl derivatives with β-cyclodextrin was also investigated. The stoichiometry of the β-cyclodextrin complexes was determined by the Job's plot method, their structure by NMR spectroscopy, and their stability by NMR and circular dichroism spectroscopy. The study of this complex opens up the possibility of a more in-depth formulation investigation. The species-specific basicity of the new potential aminoalkyl haptens was also characterized, which can help further structure-activity relationship studies.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"209 ","pages":"Article 107089"},"PeriodicalIF":4.3,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143767770","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}
引用次数: 0
Optimising electronic documentation of medication in Hungary: itemised, complete, historical, and standardised event recording.
IF 4.3 3区 医学
European Journal of Pharmaceutical Sciences Pub Date : 2025-03-31 DOI: 10.1016/j.ejps.2025.107079
Edina Hornung, Zelma Faisal, László Técsi, Andrea Lovász, Tamás Dóczi, Lajos Botz
{"title":"Optimising electronic documentation of medication in Hungary: itemised, complete, historical, and standardised event recording.","authors":"Edina Hornung, Zelma Faisal, László Técsi, Andrea Lovász, Tamás Dóczi, Lajos Botz","doi":"10.1016/j.ejps.2025.107079","DOIUrl":"https://doi.org/10.1016/j.ejps.2025.107079","url":null,"abstract":"<p><p>Hospital care is a highly complex process, requiring comprehensive documentation of all aspects of the patient journey in electronic health records. A critical component of this care is the accurate tracking of patient medications. International standards are not consistently incorporated into the electronic medication systems currently in use worldwide, and their interoperability remains an unresolved issue. We recognised the need to develop a set of standardised data elements that ensure consistent and accurate documentation. Although the medication systems studied exhibit various strengths and weaknesses and can satisfactorily document certain aspects of the medication process, none achieve the necessary level of optimal documentation. Our paper presents a new perspective on medication recording by identifying the electronic data requirements for all events in an itemized, complete, historical, and standardized manner. To address this gap, we collected, defined, and introduced the essential data elements required for the comprehensive documentation of medication sub-processes for the first time in our study. The Fast Health Interoperability Resources (FHIR) data exchange standard was employed for designing these data requirements. Our research identified and categorised 138 data elements essential for describing the complete medication process, including medication description, requests, dispensation, and administration. These data elements were divided into fundamental and supplementary categories. We developed a survey form to assess medication systems. In a pilot study, we tested the quality of 5 medication systems, currently in operation in Hungary. Our analysis assessed the accuracy of the electronic recording of medication and the correspondence of the recorded data elements with international standards. None of the systems demonstrated the ability to document medication accurately or capture all fundamental data elements. The best-performing system managed to record 63% of all fundamental data elements, while the worst-performing system managed only to document 30%. The names and the values of data elements in these systems did not comply with international standards either. The primary clinical pharmaceutical usefulness of this study was to enhance the digital documentation of medication in hospitals to meet comprehensive data recording requirements, ensure greater compliance, and improve their suitability for enriching clinical health data files, enabling real-world studies, pharmacovigilance analyses, and the identification of drug repositioning opportunities.</p>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":" ","pages":"107079"},"PeriodicalIF":4.3,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143771851","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}
引用次数: 0
Discovery of STING antagonists Targeting cGAS-STING Pathway to Alleviate IMQ-induced Psoriasis-like Dermatitis.
IF 4.3 3区 医学
European Journal of Pharmaceutical Sciences Pub Date : 2025-03-31 DOI: 10.1016/j.ejps.2025.107091
Zhixiong Zhang, Xian Wei, Qiang Huang, Zhonghua Shi, Xiaofeng Chen, Jialin Wu, Xin Wang, Jiaqi Li, Lantu Gou, Jinliang Yang
{"title":"Discovery of STING antagonists Targeting cGAS-STING Pathway to Alleviate IMQ-induced Psoriasis-like Dermatitis.","authors":"Zhixiong Zhang, Xian Wei, Qiang Huang, Zhonghua Shi, Xiaofeng Chen, Jialin Wu, Xin Wang, Jiaqi Li, Lantu Gou, Jinliang Yang","doi":"10.1016/j.ejps.2025.107091","DOIUrl":"https://doi.org/10.1016/j.ejps.2025.107091","url":null,"abstract":"<p><p>The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway is pivotal in the immune defense against infections and cancer. However, aberrant activation of this pathway can trigger autoimmune and inflammatory diseases by inducing excessive production of type I interferon (IFN) and pro-inflammatory cytokines. Inhibition of the aberrant activation of the cGAS-STING signaling pathway by targeting STING represents a novel therapeutic strategy for these autoimmune and inflammatory disorders. In this study, we discovered three novel STING antagonists based on surface plasmon resonance (SPR), differential scanning fluorimetry (DSF), and ISRE (interferon stimulated response element)-luciferase assays. The efficacy and pharmacological mechanisms of the three STING antagonists for treating imiquimod (IMQ)-induced psoriasis-like dermatitis by western blotting (WB), flow fluorescence, and immunostaining. The three STING antagonists exhibited pan-inhibitory activities on the activation of both the human and mouse cGAS-STING signaling pathway. Intravenous and topical administration of the three antagonists alleviated the inflammation and skin lesions associated with IMQ-induced psoriasis-like dermatitis via suppression of the inflammatory cascade mediated by the IMQ-TLR-7-NF-κB/cGAS-STING-NF-κB/IL-1β-IL-1R-NF-κB/TNFα-TNF-R-NF-κB signaling axis. In conclusion, we identified three novel STING antagonists with pan-inhibitory activities against human and mouse STING, providing lead compounds for the future development of both STING antagonists and immune agents for therapeutically manipulating STING-driven diseases, such as psoriasis. Our findings offer another new therapeutic strategy for managing STING-driven autoimmune and inflammatory diseases, while also reemphasizing the critical role of the cGAS-STING signaling pathway in such conditions.</p>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":" ","pages":"107091"},"PeriodicalIF":4.3,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143771738","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}
引用次数: 0
Response to the commentary on "Are all measures of liver Kpuu a function of FH, as determined following oral dosing, or have we made a critical error in defining hepatic drug clearance?"
IF 4.3 3区 医学
European Journal of Pharmaceutical Sciences Pub Date : 2025-03-31 DOI: 10.1016/j.ejps.2025.107088
Leslie Z Benet, Jasleen K Sodhi
{"title":"Response to the commentary on \"Are all measures of liver Kp<sub>uu</sub> a function of F<sub>H</sub>, as determined following oral dosing, or have we made a critical error in defining hepatic drug clearance?\"","authors":"Leslie Z Benet, Jasleen K Sodhi","doi":"10.1016/j.ejps.2025.107088","DOIUrl":"https://doi.org/10.1016/j.ejps.2025.107088","url":null,"abstract":"<p><p>Recently, Sugano commented on our above-titled publication stating that he was a reviewer for the paper. In the Acknowledgements, Sugano indicated that we \"kindly suggested publishing the reviewer report as an article\". What we had actually written was: \"prior to accepting the [unidentified] reviewer's approach, however, we believe he/she would have to publish a paper justifying the methodology and proposing how in vivo clinical data could be analyzed with such methodology\". We further explained the fallacy of the accepted mechanistic models of hepatic elimination in a subsequent manuscript titled \"Pharmacokinetic theory must consider published experimental data\", published online a month after the Sugano commentary became available -not in time for the author to review the full explanation before his commentary was published. Our above-titled publication makes no assumptions or discussions regarding how Kp<sub>uu</sub> should be measured, the major topic of the Sugano paper. Here we detail why the commentary methodology is not relevant to our demonstration that the present mechanistic models of hepatic elimination all lead to the unlikely conclusion that Kp<sub>uu</sub> cannot exceed unity and is related to F<sub>H</sub>. We also detail why the Extended Clearance Model should not be used for in vitro-in vivo extrapolation.</p>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":" ","pages":"107088"},"PeriodicalIF":4.3,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143771852","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}
引用次数: 0
Engineered-affibody conjugates contribute to the specific targeting and cellular retention of polyplexes in Erbb3 overexpressed lung cancer cells
IF 4.3 3区 医学
European Journal of Pharmaceutical Sciences Pub Date : 2025-03-31 DOI: 10.1016/j.ejps.2025.107090
Siyu Chen , Anny Nguyen , Joschka T. Müller , Müge Molbay , Aditi Mehta , Sahana Sheshachala , Kemal Baskaya , Nathan Adams , Simone Pinto Carneiro , Olivia M. Merkel
{"title":"Engineered-affibody conjugates contribute to the specific targeting and cellular retention of polyplexes in Erbb3 overexpressed lung cancer cells","authors":"Siyu Chen ,&nbsp;Anny Nguyen ,&nbsp;Joschka T. Müller ,&nbsp;Müge Molbay ,&nbsp;Aditi Mehta ,&nbsp;Sahana Sheshachala ,&nbsp;Kemal Baskaya ,&nbsp;Nathan Adams ,&nbsp;Simone Pinto Carneiro ,&nbsp;Olivia M. Merkel","doi":"10.1016/j.ejps.2025.107090","DOIUrl":"10.1016/j.ejps.2025.107090","url":null,"abstract":"<div><div>Ligand-modified nanoparticles have shown the ability to specifically bind to tumor cells, improving retention in tumors after initial accumulation driven by the enhanced permeability and retention effect. These particles are typically engineered to bind to receptors overexpressed in cancer cells compared to healthy cells, such as the HER3 (Erbb3) receptor in lung cancer. In this study, we confirmed the overexpression of Erbb3 in various <em>KRAS</em> mutant lung cancer cell lines. An engineered affibody, well-established in previous research, was selected to target Erbb3 as a proof of concept. The affibody was integrated into the particle system via two distinct strategies. In the pre-functionalization approach, the affibody was conjugated to PEI or C14-PEI using SPDP as a linker. A spectral shift technique was then used to assess the affinity of the affibody and affibody conjugates toward Erbb3, allowing us to estimate the half-maximal effective concentration (EC<em><sub>50</sub></em>). Following synthesis and characterization, various polyplex formulations were prepared, including mRNA complexes with PEI-affibody, C14-PEI/PEI-affibody, and C14-PEI/C14-PEI-affibody. In the post-functionalization approach, polyplex formulations composed of different blends of C14-PEI and functionalized Azido-PEI were initially prepared and subsequently modified with DBCO-functionalized affibody via click chemistry. These formulations were prepared at various nitrogen to phosphate (N/P) ratios and characterized in terms of particle size, polydispersity index (PDI), and zeta potential. We also evaluated cellular uptake and eGFP mRNA expression to understand how the different formulations and conjugates influenced ligand-modified polyplex properties and delivery behavior. Our results demonstrated that affibody conjugates can specifically target Erbb3 and promote polyplex accumulation in <em>KRAS</em>-mutated lung cancer cells. We further analyzed the impact of conjugation methods and affibody density on polyplex design and performance. In conclusion, this study highlights the advantages of using specific targeting ligands. By optimizing formulation components, conjugation methods, and ligand density, various targeting ligands can be attached to polyplexes, enhancing cell-specific targeting, internalization, and retention. These findings provide valuable insights and a foundation for future targeted therapies and polyplex design.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"209 ","pages":"Article 107090"},"PeriodicalIF":4.3,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143771743","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}
引用次数: 0
Quality assessment of cholic acid as an active pharmaceutical ingredient: Analytical method and results
IF 4.3 3区 医学
European Journal of Pharmaceutical Sciences Pub Date : 2025-03-30 DOI: 10.1016/j.ejps.2025.107083
Y. Polak , C.E.M. Hollak , E.L. Swart , E.M. Kemper
{"title":"Quality assessment of cholic acid as an active pharmaceutical ingredient: Analytical method and results","authors":"Y. Polak ,&nbsp;C.E.M. Hollak ,&nbsp;E.L. Swart ,&nbsp;E.M. Kemper","doi":"10.1016/j.ejps.2025.107083","DOIUrl":"10.1016/j.ejps.2025.107083","url":null,"abstract":"<div><div>Commercial cholic acid (CA) treatment is currently unavailable to Dutch patients with a bile acid synthesis defect. CA treatment has been hypothesized to correct the biochemical abnormalities associated with these disorders and potentially slowing down disease progression. To address this need, the hospital pharmacy of Amsterdam University Medical Center developed CA capsules for use in a clinical trial in The Netherlands. Challenges arose during the quality control of CA active pharmaceutical ingredient (API) as no specific substance monograph is available in the European Pharmacopoeia or other effective pharmacopoeias. In this article, we share an analytical method validated for testing the purity of CA and present the results of its quality control, offering practical guidance for ensuring adequate quality control of CA.</div><div>Pharmaceutical quality tests were performed on four batches of CA following the guidance given in the European Pharmacopoeia general monograph on substances for pharmaceutical use. The results confirm the suitability of our analytical method for CA quality control and demonstrate that the CA meets the high-quality standards required for pharmaceutical use.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"209 ","pages":"Article 107083"},"PeriodicalIF":4.3,"publicationDate":"2025-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143763480","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}
引用次数: 0
Investigating accumulation of budesonide and tacrolimus in an ex vivo porcine oesophageal model: Translational potential for local application of drugs to treat eosinophilic oesophagitis
IF 4.3 3区 医学
European Journal of Pharmaceutical Sciences Pub Date : 2025-03-30 DOI: 10.1016/j.ejps.2025.107086
Farhan Taherali , Marissa Taub , Felipe Varum , Roberto Bravo , Abdul W Basit
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