European Journal of Pharmaceutical Sciences最新文献

{"title":"Development of a controlled-release tofacitinib formulation using acid-sensitive pore-forming components for an osmotic drug delivery system","authors":"Jin Ah Lee ,&nbsp;Yun Jung Lee ,&nbsp;Jeong A Seong ,&nbsp;Myung Kwan Chun ,&nbsp;Kwon Yeon Weon","doi":"10.1016/j.ejps.2025.107389","DOIUrl":"10.1016/j.ejps.2025.107389","url":null,"abstract":"<div><div>Acid-sensitive ingredient porosity osmotic drug delivery systems (AID) are a simplified and scalable alternative to conventional ODDS. In the current study, the tofacitinib-loaded AID formulation was optimized using an I-optimal mixture design. The three coating excipients examined as independent variables were cellulose acetate (X₁; 25.8–43.8 %), sodium bicarbonate (X₂; 20.0–30.0 %), and hydroxypropyl cellulose (X₃; 26.3–46.3 %). Response variables included cumulative drug release at 2 h (Y₁), 4 h (Y₂), and 8 h (Y₃), as well as the percentage of residual drug after 8 h (Y₄), which were analyzed using a quadratic model within the I-optimal framework. The coefficient of determination (R²) values for Y₁, Y₂, Y₃, and Y₄ were 0.79, 0.74, 0.55, and 0.48, respectively. The optimized AID exhibited zero-order drug release kinetics (R² = 0.9931), with a release rate constant (K₀) of 0.20 h⁻¹, indicating a consistent and controlled release profile throughout the evaluation period. Pharmacokinetic studies indicated no significant lag time for the AID, while Xeljanz® XR 11 mg exhibited an initial lag time of approximately 0.64 h, consistent with the characteristics of conventional ODDS technologies. Maximum plasma concentrations (C_max) were 75.7 ± 40.8 ng/mL for Xeljanz® XR 11 mg and 79.4 ± 37.1 ng/mL for AID. The areas under the plasma concentration-time curve were 610.0 ± 187.5 ng/mL for Xeljanz® XR 11 mg and 586.1 ± 210.5 ng/mL for AID. Times to maximum plasma concentration were 5 h for Xeljanz® XR 11 mg and 2 h for AID. Collectively, this modified approach reduces the initial lag time and allows for faster drug action.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"217 ","pages":"Article 107389"},"PeriodicalIF":4.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145631391","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":"Enhanced nuclear enrichment of chemotherapeutics by a biomimetic ZIF-8 nanosystem for multidrug-resistant cancer treatment","authors":"Jingyan Hu ,&nbsp;Jieting Wang ,&nbsp;Junyang Zhuang ,&nbsp;Heng Zhu ,&nbsp;Ao Zhou ,&nbsp;Jingyan Jia ,&nbsp;Xueyang Ji ,&nbsp;Yan Zhao ,&nbsp;Luying Yu ,&nbsp;Yu Deng ,&nbsp;Ning Li ,&nbsp;Fang Wang","doi":"10.1016/j.ejps.2025.107396","DOIUrl":"10.1016/j.ejps.2025.107396","url":null,"abstract":"<div><div>The exclusion of chemo-drugs from their target sites, <em>e.g.</em> the nucleus, is a critical factor contributing to the failure of chemotherapy. Nanoparticle-based technology holds promise for specific delivery of chemo-drugs to nucleus. However, limited lysosomal escape, small size of nuclear pores and incapability of direct regulation of drug efflux-related transporters made great challenges for nanoparticles. Here, a zeolitic imidazolate framework-8 (ZIF-8)-based nanosystem was found able to disrupt lysosomes by the pH-responsiveness of ZIF-8 and mediate the nuclear entry of chemotherapeutics through promotion of their passive diffusion, resulting in the decrease of half maximal inhibitory concentration (IC50) by 3.4-fold compared to free drugs. The additional encapsulation of small interfering RNA (siRNA) to specifically silence multidrug resistance gene 1 (MDR1) for reduction of drug efflux further enhanced the chemotherapy of cancer with multidrug resistance (MDR) (IC50 reduced by 5.2-fold compared to free drugs). With a macrophage membrane biosurface coating onto the nanoparticles, targeted and potent synergistic chemo-gene therapy was achieved in mice bearing cancer with MDR. The unique function of promoting chemotherapeutic nuclear accumulation by ZIF-8-based nanoparticles to fight against MDR may deepen our understanding of the nano/bio-interactions and give novel insights into the design of smart bioresponsive nanosystems for advanced therapy.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"217 ","pages":"Article 107396"},"PeriodicalIF":4.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145687189","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 of an in situ forming methylcellulose hydrogel as universal vehicle for preclinical intravitreal injection of particulate formulations","authors":"Marco Block ,&nbsp;Grazia Giorgio ,&nbsp;Christoph Saal ,&nbsp;Remko A. Bakker ,&nbsp;Achim Goepferich ,&nbsp;Achim Grube ,&nbsp;Roman Simon","doi":"10.1016/j.ejps.2025.107346","DOIUrl":"10.1016/j.ejps.2025.107346","url":null,"abstract":"<div><div>Preclinical development of novel intravitreal pharmaceuticals is reliant on the use of animal pharmacokinetic (PK) and pharmacodynamic (PD) models, incipiently performed in small rodents. As most novel molecular entities exhibit fast intravitreal clearance, tailored preclinical extended-release (XR) formulations like microparticle suspensions are required to ensure sufficient exposure in the eye for 1 – 4 weeks which are required for PD experiments. Still, their use is very limited due to three major drawbacks: (i) Limited injectability of high particle concentrations, (ii) high intravitreal mobility, and (iii) attachment to vitreoretinal tissues and the lens. (ii) and (iii) complicate or prohibit PK and PD readouts.</div><div>We developed a universal hydrogel vehicle to specifically enable microparticulate XR formulations for preclinical intravitreal injection. By optimizing the interplay of methylcellulose and kosmotropic additives, namely Na-citrate and Na-tartrate, rapid thermal gelation at vitreous temperature of 34 °C was ensured. The hydrogel vehicle enabled injection of microparticulate XR formulations (Poly-lactide-co-glycolide and silica matrix particles) even when using non-siliconized syringes with small 34 gauge needles. Reduced intravitreal mobility and facilitated separation of formulation from retinal tissues was demonstrated <em>ex vivo</em> in porcine eyes. Rheological examination validated almost complete obstruction of embedded particulate XR formulations. <em>In vitro</em> XR of drugs (small molecules up to full length antibodies) was not altered. Experiments on ARPE-19 cells <em>in vitro</em> showed good tolerability and low toxicity. Furthermore, the hydrogel vehicle masked the cytotoxicity of embedded silica microparticles in high concentration. Our results suggest the hydrogel vehicle as a highly promising universal vehicle for preclinical intravitreal injection.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"217 ","pages":"Article 107346"},"PeriodicalIF":4.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145367735","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":"Preclinical safety assessment of holmium-based microspheres for micro-brachytherapy in mice","authors":"Nienke Johanna Maria Klaassen ,&nbsp;Milou Boswinkel ,&nbsp;Nino Chiron Morsink ,&nbsp;Alexandra Gil Arranja ,&nbsp;Guillaume Cornelis Maria Grinwis ,&nbsp;Janneke Molkenboer-Kuenen ,&nbsp;Jan Willem Hesselink ,&nbsp;Sebastiaan Alexander van Nimwegen ,&nbsp;Johannes Frank Wilhelmus Nijsen","doi":"10.1016/j.ejps.2025.107419","DOIUrl":"10.1016/j.ejps.2025.107419","url":null,"abstract":"<div><h3>Introduction</h3><div>Holmium-166 microspheres are suitable for micro-brachytherapy for various solid tumours, due to their favourable characteristics regarding treatment and imaging. The purpose of this study was to investigate acute- to long-term toxicity, 3 days to 12 months, biodegradation and <em>in vivo</em> holmium release of two types of holmium-based microspheres, containing poly(L-lactic acid) (Ho-PLLA-MS) or hydroxide (Ho-(OH)₃−MS), homogeneously suspended in an injection fluid comprised by colloidal microcrystalline cellulose (MCC) and phosphate buffer in healthy mice.</div></div><div><h3>Methods</h3><div>250 mice were included in the study. Non-radioactive holmium-165 microsphere suspensions, were injected subcutaneously on the flank of 150 mice, animals were intensively monitored. CT imaging was performed to visualise the location of the injection site, the distribution of the microspheres and the injection fluid and their possible translocation. Injection site and other relevant tissues were assessed histologically and possible holmium leakage or microsphere migration was examined by analysing the holmium content in the injection site and relevant tissues via inductively coupled plasma analysis (ICP).</div></div><div><h3>Results</h3><div>The injection of holmium-165 microspheres suspended in MCC-based injection fluid caused local inflammation ranging from slight to severe. No relevant deviations in haematological or biochemical parameters indicative for acute or chronic systemic toxicity were observed. ICP analysis and CT imaging showed no signs of microsphere translocation from the injection site to other organs.</div></div><div><h3>Conclusion</h3><div>These findings indicate that the injection fluid (MCC in phosphate buffer) in combination with Ho-(OH)₃−MS or Ho-PLLA-MS can potentially be used as administration fluid for controlled localized microsphere delivery. However, prior to clinical application, clinically relevant doses have to be tested in sensitive anatomical regions.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"217 ","pages":"Article 107419"},"PeriodicalIF":4.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145793553","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":"Single-dose pharmacokinetics of sublingual semaglutide in rats","authors":"Yi Liu ,&nbsp;Guiyun Song ,&nbsp;Daniel Banov ,&nbsp;Jennifer Denison ,&nbsp;Courtaney Davis ,&nbsp;Kendice Ip","doi":"10.1016/j.ejps.2025.107406","DOIUrl":"10.1016/j.ejps.2025.107406","url":null,"abstract":"<div><div>This study aims to compare the single-dose pharmacokinetic profiles of semaglutide administered via sublingual, oral, and injectable routes in Sprague–Dawley rats. Semaglutide was delivered sublingually in a proprietary anhydrous suspension vehicle. Rats were randomized into five groups and received the following treatments: subcutaneous injection (0.011 mg/kg), sublingual suspension (1 mg/kg, prepared from either commercial tablets or peptide powder), and oral tablets (1 mg/kg and 20 mg/kg). Semaglutide was detectable in plasma within 2 minutes post-dosing in all groups except the oral 1 mg/kg group. Sublingual administration demonstrated lower variability in plasma concentrations compared to oral dosing. At 1 mg/kg, the sublingual route achieved a significantly higher area under the curve (AUC) than oral (82.53 <em>vs.</em>15.08 ng*h/ml, <em>p</em>=0.004), indicating improved bioavailability. The maximum plasma concentration (C_max) was reached within 30 minutes for oral and sublingual routes, and at 8 hours for subcutaneous injection. The relative bioavailability was 0.06% for oral 1 mg/kg, 0.16% for oral 20 mg/kg, and 0.34% and 0.29% for sublingual 1 mg/kg using tablets or powder, respectively. No significant difference in AUC was observed between sublingual semaglutide prepared from oral tablets <em>versus</em> powder. These results highlight the potential of sublingual delivery of semaglutide and suggest this route may improve absorption while reducing variability. This proof-of-concept study supports further development of sublingual semaglutide formulations and pharmacokinetics research in humans.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"217 ","pages":"Article 107406"},"PeriodicalIF":4.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145735623","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 a forward design-based multi-attribute decision-making method in quality assessment in pharmaceutical tablet manufacturing","authors":"Xinhao Wan ,&nbsp;Ming Yang ,&nbsp;Zhijian Zhong ,&nbsp;Xiaoqing Zhou ,&nbsp;Xuecheng Wang ,&nbsp;Qing Tao ,&nbsp;Zhenfeng Wu","doi":"10.1016/j.ejps.2025.107392","DOIUrl":"10.1016/j.ejps.2025.107392","url":null,"abstract":"<div><div>With the modernization of the pharmaceutical industry and increasingly stringent regulatory requirements, ensuring the quality and process stability of pharmaceutical tablets has become a critical challenge. In particular, chewable tablets, as a unique type of oral solid dosage form designed to be chewed before swallowing, require special attention to mechanical properties and sensory attributes such as texture, mouthfeel, and taste acceptability. This study aims to implement a forward design-based multi-attribute decision-making (MADM) framework for systematic and accurate multi-criteria quality assessment and prediction of pharmaceutical chewable tablets. Tablets were produced using batch-based tableting technology, and critical quality attributes—including weight variation, friability, porosity, and hardness—were systematically evaluated under varying process conditions. Tensile strength was employed as an external validation index. To overcome the limitations of traditional evaluation methods, the proposed MADM framework incorporates a game theory (GT)-based combinatorial weighting strategy, effectively integrating subjective experience-based judgment with objective data-driven metrics. In addition, a backpropagation neural network (BPNN) model was developed to capture the nonlinear relationships between process parameters and the comprehensive quality index. Compared to conventional weighting approaches such as the analytic hierarchy process (AHP), entropy method (EM), and mean-based weighting, the GT-based strategy demonstrated superior performance in terms of evaluation robustness and accuracy. The MADM results showed strong agreement with the tensile strength data, confirming the reliability and consistency of the evaluation framework. Furthermore, the BPNN model achieved high prediction accuracy, providing solid quantitative support for process optimization. Overall, the proposed method offers a robust and generalizable solution for multi-criteria quality assessment and prediction of pharmaceutical chewable tablets. When integrated with industrial information systems, it enables data-driven optimization, intelligent quality control, and automation, thereby contributing to the advancement of smart pharmaceutical manufacturing.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"217 ","pages":"Article 107392"},"PeriodicalIF":4.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145654019","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":"Longitudinal monitoring of nanofibrillar cellulose hydrogel medical implants in mice using positron emission tomography","authors":"Xiaoqing Zhuang ,&nbsp;Jenni Virta ,&nbsp;Heidi Liljenbäck ,&nbsp;Lauri Paasonen ,&nbsp;Anu J. Airaksinen ,&nbsp;Anne Roivainen ,&nbsp;Xiang-Guo Li","doi":"10.1016/j.ejps.2025.107402","DOIUrl":"10.1016/j.ejps.2025.107402","url":null,"abstract":"<div><div>Nanofibrillar cellulose (NFC) hydrogel has emerged as a promising implantable material for therapeutic applications. In this study, the relatively longer-lived positron-emitting radionuclide zirconium-89 was chelated to the octadentate deferoxamine (DFO*)-conjugated NFC hydrogel ([⁸⁹Zr]Zr-DFO*-NFC) to enable longitudinal monitoring of its <em>in vivo</em> fate using positron emission tomography techniques. Following subcutaneous implantation in healthy mice, [⁸⁹Zr]Zr-DFO*-NFC retained radioactivity at the implant site for at least 14 days, with minimal signal detected in the kidneys, urinary bladder, and overlying skin. In contrast, mice receiving a control formulation of [⁸⁹Zr]Zr-oxalate mixed with NFC hydrogel showed progressive accumulation of radioactivity in the bones, consistent with known [⁸⁹Zr]Zr-oxalate distribution patterns, and only limited retention at the implant site by Day 7. These findings demonstrate that [⁸⁹Zr]Zr-DFO*-NFC hydrogel implants exhibit high <em>in vivo</em> stability with negligible systemic release following subcutaneous implantation, supporting their potential use as safe and traceable biomaterial platforms.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"217 ","pages":"Article 107402"},"PeriodicalIF":4.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145707293","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":"Comparative analysis of irradiation technologies on high-density polyethylene (HDPE) for biopharmaceutical applications","authors":"Blanche Krieguer ,&nbsp;Fabien Girard ,&nbsp;Samuel Dorey ,&nbsp;Nathalie Dupuy ,&nbsp;Sylvain R.A. Marque","doi":"10.1016/j.ejps.2025.107394","DOIUrl":"10.1016/j.ejps.2025.107394","url":null,"abstract":"<div><div>The impacts of e-beam and X-ray irradiation on medical-grade high-density polyethylene (HDPE) are compared with that of gamma irradiation to evaluate their potential effects on pharmaceutical applications. An extensive suite of analytical techniques was employed to evaluate the chemical and physical transformations of irradiated HDPE. Key findings indicated that irradiation did not significantly alter the mechanical properties, as tensile strength and elongation at break remained stable across all irradiation types and doses. Thermal analysis via Differential Scanning Calorimetry (DSC) revealed a slight decrease in melting temperature at higher doses, with an equivalent melting temperature peak observed for all three irradiation technologies. Electron Spin Resonance (ESR) detected alkyl and allyl radicals, which decreased over time, showing no significant differences attributable to irradiation type or dose. Colorimetric analysis indicated yellowing in the samples, linked to specific additives. The quantification of methionine oxidized byproducts by High-Performance Liquid Chromatography (HPLC) demonstrated that the oxidation potential was equivalent for the three irradiation technologies for HDPE. The study concluded that there was a lack of significant impact of irradiation technologies on several physical, chemical and mechanical properties of HDPE.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"217 ","pages":"Article 107394"},"PeriodicalIF":4.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145676725","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":"Elucidating the roles of TM7SF3 and LHFPL6 in the putative H+/OC antiporter function in the human brain capillary endothelial cell line, hCMEC/D3","authors":"Nana Svane ,&nbsp;Toshiki Kurosawa ,&nbsp;Benjamin Schmid ,&nbsp;Lasse Saaby ,&nbsp;Mie Kristensen ,&nbsp;Hidetsugu Tabata ,&nbsp;Yoshiyuki Kubo ,&nbsp;Tetsuya Terasaki ,&nbsp;Birger Brodin ,&nbsp;Yoshiharu Deguchi","doi":"10.1016/j.ejps.2025.107409","DOIUrl":"10.1016/j.ejps.2025.107409","url":null,"abstract":"<div><h3>Introduction</h3><div>The putative proton/organic cation (H⁺/OC) antiporter has been shown to mediate transport of CNS drug compounds like oxycodone and pyrilamine across the blood-brain barrier (BBB). This transporter has a broad substrate profile and is able to transport substrates against their concentration gradient, making it an interesting target for brain drug delivery. However, the molecular identity of this transporter remains unknown. Recent studies have indicated that the two proteins TM7SF3 and LHFPL6 might be components of this transporter. The present study aimed to investigate the roles of TM7SF3 and LHFPL6 in the H⁺/OC antiporter function to advance understanding of its molecular identity and potential in CNS drug delivery.</div></div><div><h3>Methods</h3><div>CRISPR-Cas9 gene-editing was used to generate three hCMEC/D3 knockout (KO) cell lines: TM7SF3 KO (TM-KO), LHFPL6 KO (LH-KO), and a double KO of TM7SF3 and LHFPL6 (TMLH-KO). The uptake of pyrilamine analogue (EDMPG) and [³H]-pyrilamine was assessed in wild type (WT) and KO lines. Quantitative Realtime Polymerase Chain Reaction (qRT-PCR) confirmed successful gene knockouts. Passive diffusion properties and the expression and functionality of known BBB transporters, including LAT1 (<em>SLC7A5</em>), GLUT1 (<em>SLC2A1</em>), and MCT1 (<em>SLC16A1</em>), were also examined.</div></div><div><h3>Results</h3><div>The EDMPG uptake was significantly reduced in TM-, LH-, and TMLH-KO cells, suggesting that TM7SF3 and LHFPL6 contribute to the H⁺/OC antiporter function. However, [³H]-pyrilamine uptake remained unchanged across all KOs, indicating a TM7SF3- and LHFPL6-independent transport mechanism. This was further supported by the persistent inhibition of [³H]-pyrilamine uptake in the presence of known H⁺/OC antiporter substrates. While passive diffusion and GLUT1- and MCT1-mediated transport were unaffected, LAT1-mediated uptake of [³H]L-leucine and gabapentin (Neurontin) was significantly reduced in LH- and TMLH-KO cells, correlating with decreased LAT1 mRNA expression in these cells.</div></div><div><h3>Conclusions</h3><div>This study suggests that the <em>H</em>+/OC antiporter operates via two distinct mechanisms: a high-capacity, TM7SF3- and LHFPL6-independent pathway and a low-capacity, TM7SF3- and LHFPL6-dependent pathway. These findings underscore the complexity of the H⁺/OC antiporter molecular composition and highlight the need for further research to fully elucidate its identity.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"217 ","pages":"Article 107409"},"PeriodicalIF":4.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145741596","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":"Influence of 3-, 4- and 6-layered borophene on biocompatibility with “non-professional” human phagocytes","authors":"Dariusz Wawrzyniak ,&nbsp;Klaudia Zielinkiewicz ,&nbsp;Ewa Mijowska ,&nbsp;Katarzyna Rolle ,&nbsp;Elżbieta Czarniewska","doi":"10.1016/j.ejps.2025.107335","DOIUrl":"10.1016/j.ejps.2025.107335","url":null,"abstract":"<div><div>The medical application of borophene in fields such as <em>in vivo</em> diagnosis, drug delivery, and photochemical therapy of cancer requires detailed assessment. There is no knowledge about its effects on cells, organs, and the whole organism of humans and animals. It can be assumed that the impact of borophene on cells will be correlated with the aspect ratio of the 2D flakes and their thickness. This study sought to determine if these nanomaterials are biocompatible and, if not, whether their cytotoxicity is caused by their thickness, dosage, or exposure duration in the model cells employed in the study. The influence of 3-, 4- or 6-layer borophene in the concentration range from 0.2 to 1 mg/ml of the medium on the morphology, integrity of the cell membrane, induction of apoptosis and reactive oxygen species and the level of reducing power in MRC-5 cells was investigated. The study showed no effect of borophene on the plasma membrane, no cytotoxic effects leading to apoptosis or necrosis of MRC-5 cells even at high doses of tested nanomaterials and regardless of the number of layers. Borophene had a beneficial effect on human fibroblasts because it increased or did not change the level of reducing power, which balanced of oxidative stress in cells, if induced. These effects allowed maintaining cell viability and functionality. This study opens up research perspectives leading to understanding the mechanisms responsible for maintaining viability in the borophene-exposed cells. The question remains whether borophene is biocompatible in other models, <em>e.g.</em>, non-phagocytic cells, and what other molecular mechanisms are involved in maintaining the viability of the borophene-exposed cells. If the biocompatibility of borophene with a wide range of cells is confirmed, it will find numerous applications in biomedicine with special emphasis on Boron Neutron Therapy.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"217 ","pages":"Article 107335"},"PeriodicalIF":4.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145336438","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}