European Journal of Pharmaceutical Sciences最新文献

{"title":"Pharmacokinetic profile of dexamethasone in urine and plasma after single and multiple oral administration: Relevance to doping controls","authors":"Sergi Coll ,&nbsp;Claudia Bressan ,&nbsp;Núria Monfort ,&nbsp;Ana Aldea-Perona ,&nbsp;Marcel·lí Carbó ,&nbsp;Rosa Ventura","doi":"10.1016/j.ejps.2025.107405","DOIUrl":"10.1016/j.ejps.2025.107405","url":null,"abstract":"<div><div>Dexamethasone (DEX) is prohibited in sports competitions when administered by all injectable, oral or rectal routes, and is permitted at all times when administered by all other routes. The present work aimed to assess the urinary excretion profile of DEX after single and multiple oral administrations to verify the suitability of the new minimum reporting level (MRL) of 60 ng/mL established by the World Anti-Doping Agency to distinguish allowed and prohibited administrations. Moreover, the minimum washout period of three days established for out-of-competition treatments with oral glucocorticoids will be evaluated.</div><div>DEX was administered to healthy volunteers using two different oral treatments: single administration (4 mg, <em>n</em> = 8 male volunteers) and multiple administrations (2 mg/12 h for 5 days, <em>n</em> = 8 male volunteers). Urine and plasma samples collected before and after administration were analysed using liquid chromatography-tandem mass spectrometry. DEX and 6β‑hydroxy-DEX, were the predominant compounds detected in urine, with peak urinary excretion observed within the first 4 h post-dose. DEX concentrations exceeded the new MRL mainly within 12 h after a single dose, with one volunteer showing levels above this threshold up to 24–36 h. In the multiple-dose study, most of the DEX concentrations remained above 60 ng/mL after the second dose and throughout the dosing period and declined quickly after the final dose. Plasma DEX kinetics was defined by an open bicompartmental model with a first order oral absorption. DEX was detectable up to 48 h post-administration. In the multiple dose study, the steady-state concentrations were reached soon after the first dose, and DEX showed no evidence of accumulation. CORT levels decreased rapidly after both single and multiple administrations due to suppression of the hypothalamic-pituitary-adrenal axis. Recovery times varied among volunteers.</div><div>The MRL of 60 ng/mL proved appropriate for distinguishing permitted from prohibited use with a 3-day washout, though further studies on non-systemic routes are recommended to refine sensitivity.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"217 ","pages":"Article 107405"},"PeriodicalIF":4.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145721647","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":"Update on clinical trials of intra-articular disease-modifying osteoarthritis drugs inducing cartilage regeneration","authors":"Luca Morici ,&nbsp;Ines Nikolic","doi":"10.1016/j.ejps.2025.107403","DOIUrl":"10.1016/j.ejps.2025.107403","url":null,"abstract":"<div><div>Osteoarthritis is the most common degenerative joint disease affecting millions of people in the world and leading to disability. Currently, the only available treatments on the market are symptomatic therapies for pain and inflammation. There are no intra-articular drugs that can restore the cartilage matrix, also known as disease-modifying osteoarthritis drugs (DMOADs). This review focuses on all clinical trials of pro-anabolic DMOADs, which stimulate the regeneration of the cartilage matrix by inducing the differentiation of mesenchymal progenitors into chondrocytes, a process known as chondrogenesis. This review also discussed some pathways of chondrocytes, which boost the transcription of genes involved in the production of extracellular matrix components. Finally, the review also covers some implants in the commercial and clinical phases for cartilage repair.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"217 ","pages":"Article 107403"},"PeriodicalIF":4.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145721731","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":"ASIC3–PLCG1 axis–driven macropinocytosis promotes osimertinib drug-tolerant persistence in malignant pleural effusion–associated NSCLC","authors":"Wen‐Chien Huang ,&nbsp;Chieh-Yung Wang ,&nbsp;Ying Chen ,&nbsp;Yi-Hsuan Lin ,&nbsp;Chih-Ying Changchien ,&nbsp;Chih-Feng Chian ,&nbsp;Chen-Liang Tsai","doi":"10.1016/j.ejps.2025.107417","DOIUrl":"10.1016/j.ejps.2025.107417","url":null,"abstract":"<div><h3>Background</h3><div>Non-small cell lung cancer (NSCLC) frequently develops resistance to EGFR-tyrosine kinase inhibitors (TKIs), particularly in malignant pleural effusion (MPE), where a highly acidic tumor microenvironment promotes the emergence of drug-tolerant persister (DTP) cells. Building upon previous evidence that MPE acidity drives metabolic plasticity, this study investigates how acid-sensing ion channel 3 (ASIC3) coordinates PLCG1-dependent macropinocytosis to maintain osimertinib tolerance.</div></div><div><h3>Methods</h3><div>Primary MPE-derived NSCLC cultures underwent next-generation sequencing to define mutational heterogeneity. Acidic (pH 6.5–6.8) conditions were used to generate osimertinib-induced DTP (Osi-DTP) models. Functional assays assessed viability, invasion, colony formation, autophagy, and macropinocytosis. ASIC3 was silenced using shRNA, followed by Seahorse metabolic analysis. Transcriptomic profiling identified differentially expressed genes. ASIC3-targeted therapeutic interventions were evaluated <em>in vitro</em> and in xenograft models.</div></div><div><h3>Results</h3><div>MPE-derived NSCLC cultures showed substantial genomic diversity, including EGFR exon 19 deletion and T790M mutations. Acid-adapted Osi-DTP cells exhibited EMT-like phenotypes, reduced proliferation, elevated stemness markers, and strong activation of stress-response pathways. ASIC3 was consistently upregulated under acidic conditions and drove PLCG1-mediated macropinocytosis to support nutrient scavenging and survival. ASIC3 knockdown markedly reduced DTP cell viability, invasiveness, colony formation, autophagy, and glycolysis, while inducing a metabolic shift toward oxidative phosphorylation. In vivo, combining an ASIC3 inhibitor with osimertinib significantly delayed tumor progression and improved survival without added toxicity. Clinically, high ASIC3 expression correlated with poor overall survival and increased autophagy-associated markers.</div></div><div><h3>Conclusion</h3><div>ASIC3 is a central regulator of acidosis-driven drug persistence in MPE-associated NSCLC, sustaining osimertinib tolerance through PLCG1-dependent macropinocytosis and metabolic reprogramming. Targeting ASIC3 restores TKI sensitivity by disrupting nutrient acquisition, autophagy, and metabolic adaptation, representing a promising therapeutic strategy to prevent or delay EGFR-TKI resistance.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"217 ","pages":"Article 107417"},"PeriodicalIF":4.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145793577","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":"Mechanistic insights into semi-solid extrusion 3D printing of indomethacin-nicotinamide cocrystal-loaded oral fast-dissolving films","authors":"Maha F. Emam ,&nbsp;Elina Harju ,&nbsp;Atte Junnila ,&nbsp;Kirsi Mikkonen ,&nbsp;Teemu Tomberg ,&nbsp;Clare Strachan ,&nbsp;Anssi-Pekka Karttunen ,&nbsp;Leena Peltonen","doi":"10.1016/j.ejps.2025.107404","DOIUrl":"10.1016/j.ejps.2025.107404","url":null,"abstract":"<div><div>The growing demand for personalized medicine requires adaptable dosage forms capable of addressing challenges associated with poorly soluble drugs. Cocrystals offer a powerful strategy to enhance solubility, while semi-solid extrusion (SSE) 3D printing enables flexible, patient-tailored manufacturing. This study establishes a systematic framework for developing oral fast-dissolving films (OFDFs) incorporating indomethacin–nicotinamide (IND–NIC) cocrystals using SSE 3D printing. Critical Material Attributes (CMAs), HPMC–glycerol base, sodium starch glycolate (SSG), and varying cocrystal loadings, were systematically adjusted to evaluate their influence on key ink and film Critical Quality Attributes (CQAs).</div><div>All inks displayed desirable shear-thinning behaviour, with IND–NIC cocrystals and SSG synergistically reinforcing the structural network for reliable extrusion and shape fidelity. Solid-state analyses (XRPD, DSC, PLM, Raman microscopy) confirmed preservation of the cocrystal form throughout ink preparation, printing, and short-term storage. The 3D printed OFDFs exhibited uniform thickness, weight, and drug content with minimal variability across batches, and displayed humidity-dependent mechanical behaviour that varied with cocrystal loading.</div><div>All formulations achieved rapid drug release, exceeding 80 % IND dissolution within 30 min. Dissolution profiles were consistent across cocrystal loadings and remained statistically equivalent for films printed from inks stored for up to 2 days, as well as for the 3-day redispersed ink, confirming that the structural reinforcement required for printability does not compromise rapid release performance.</div><div>Overall, this work provides mechanistic insight into the formulation–process–performance relationships governing SSE 3D printing of cocrystal-loaded OFDFs and highlights the potential of this green, low-temperature platform for decentralized, patient-centric manufacturing of fast-dissolving dosage forms.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"217 ","pages":"Article 107404"},"PeriodicalIF":4.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145721582","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":"Comparing iron sucrose and ferric carboxymaltose interactions with murine and human macrophages: Focus on the lysosomal compartment","authors":"Mauro Sousa de Almeida ,&nbsp;Amélie Bazzoni ,&nbsp;Sandor Balog ,&nbsp;Kata Dorbic ,&nbsp;Céline Loussert-Fonta ,&nbsp;Aura Maria Moreno-Echeverri ,&nbsp;Jules Duruz ,&nbsp;Jorge Larios ,&nbsp;Anne-Marinette Cao ,&nbsp;Amy Barton Alston ,&nbsp;Reinaldo Digigow ,&nbsp;Beat Flühmann ,&nbsp;Alke Petri-Fink ,&nbsp;Barbara Rothen-Rutishauser","doi":"10.1016/j.ejps.2025.107390","DOIUrl":"10.1016/j.ejps.2025.107390","url":null,"abstract":"<div><div>Intravenous iron drugs are commonly used in the treatment of iron deficiency/iron deficiency anaemia. However, the cellular mechanisms underlying the uptake of these complexes remain poorly understood. This study examines the interaction of two iron complexes, iron sucrose and ferric-carboxymaltose, with murine J774A.1 and human M2a macrophages, focusing on their uptake and localization within lysosomal compartments at various time points: 45 min, 6 h, 24 h, and 5 days. We employed multiple analytical methods, including Prussian blue staining and transmission electron microscopy, to assess the intracellular iron complexes. In addition, the stability of the two complexes in cell culture medium and artificial lysosomal fluid was assessed by dynamic light scattering and transmission electron microscopy. A formation of larger aggregates for both complexes in cell culture medium was observed, likely due to interactions with serum proteins. The analysis in artificial lysosomal fluid revealed a slight, but not statistically significant, decrease in hydrodynamic diameter. Upon interaction with macrophages, our results demonstrate that iron sucrose is internalized more rapidly by both macrophage cell types compared to ferric carboxymaltose. Furthermore, the detection of ferric ions within intracellular and intralysosomal compartments occurs at a later time point following macrophage exposure to ferric carboxymaltose, suggesting slower internalization in comparison to iron sucrose. Our findings suggest that the two complexes remain intact upon reaching macrophages and, after internalization, are localized within intracellular vesicles, indicating endocytosis as the primary uptake mechanism. Iron sucrose was internalized more rapidly in comparison to ferric carboxymaltose by both macrophage types, whereas a decrease in metabolic activity was only observed for the J774A.1 macrophages in the presence of high iron sucrose concentration, <em>i.e.</em>, 1mg/mL iron. These findings provide new insights into the dynamics of different iron-carbohydrate complexes on cellular uptake and may contribute to optimizing future drug designs.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"217 ","pages":"Article 107390"},"PeriodicalIF":4.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145647884","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":"Synthesis, in vitro characterization and biopharmaceutical evaluation of a novel phosphate prodrug of sorafenib","authors":"Simon Hoang Dinh ,&nbsp;Christian Ding Fisker ,&nbsp;Juulia Järvinen ,&nbsp;Kati-Sisko Vellonen ,&nbsp;Annette Bauer-Brandl ,&nbsp;Poul Nielsen ,&nbsp;Jarkko Rautio ,&nbsp;Martin Brandl","doi":"10.1016/j.ejps.2025.107397","DOIUrl":"10.1016/j.ejps.2025.107397","url":null,"abstract":"<div><div>Sorafenib is a multi-kinase inhibitor approved for several cancers with poor aqueous solubility, resulting in low oral bioavailability (38–49 %) despite its high permeability. As a BCS Class II compound, its absorption is solubility-/dissolution-limited. Prodrug strategies, such as phosphate esterification, can improve solubility and promote oral bioavailability upon enzymatic cleavage by intestinal alkaline phosphatase (IALP), abundantly expressed at the intestinal brush border membrane and present in the intestinal lumen. This cleavage is hypothesized to lead to a transient supersaturation of the parent drug, enhancing absorption unless (premature) precipitation prevails. Besides traditional in vitro models like Caco-2 cells, recently microdialysis-sampling has been introduced to study ALP-mediated biomimetic conversion of oral phosphate prodrugs in vitro. Microdialysis enables real-time, non-destructive sampling of molecularly dissolved drug, which allows to study the complex inter-related dynamics under (simulated) human gastrointestinal conditions.</div><div>In this study, a novel and new phosphate prodrug of sorafenib (fossorafenib) was synthesized and its physico-chemical and biopharmaceutical properties were evaluated. Fossorafenib exhibited ∼600-fold higher aqueous solubility than sorafenib in HBSS pH 7.4 and was rapidly cleaved by externally added alkaline phosphatase (ALP), yielding supersaturated sorafenib. Combined cleavage &amp; permeability studies across Caco-2 cell monolayers demonstrated rapid bioconversion of fossorafenib in the apical compartment, with permeation of both the converted parent drug but, surprisingly, also the prodrug. Microdialysis enabled real-time monitoring of the biomimetic conversion of fossorafenib without the requirement for enzyme inactivation, thereby allowing for unprecedented mechanistic insights into the interplay between micellar solubilization and enzymatic cleavage. Microdialysis results suggest that micellar incorporation of fossorafenib into mixed micelles of bile salts and phospholipids can hinder enzymatic cleavage by intestinal ALP, thereby potentially limiting the extent of prodrug activation in the intestinal environment. Taken together with the unexpected ability of the prodrug to cross biological/biomimetic barriers, these findings suggest that fossorafenib may not follow the conventional behavior of classical phosphate-ester oral prodrugs in vivo, highlighting the need for further investigation into its unique biopharmaceutical profile.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"217 ","pages":"Article 107397"},"PeriodicalIF":4.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145695903","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":"Individualized dosing strategies in breast cancer chemotherapy: Evidence for therapeutic drug monitoring-guided docetaxel treatment","authors":"Ya-Min Liu ,&nbsp;Wei Huang ,&nbsp;Yong-Zhe Tang ,&nbsp;Hai Zhang ,&nbsp;Sheng-Ying Qin ,&nbsp;Jin Zhang ,&nbsp;Jun-Wei Fan ,&nbsp;Rui-Zhuo Ouyang ,&nbsp;Hai-Ou Yang ,&nbsp;Xiao-Qing Zhang","doi":"10.1016/j.ejps.2025.107407","DOIUrl":"10.1016/j.ejps.2025.107407","url":null,"abstract":"<div><h3>Background</h3><div>Docetaxel is a first-line chemotherapy drug for breast cancer and is traditionally dosed based on body surface area (BSA). However, this method often leads to significant inter-patient variability and a high incidence of adverse drug reactions (ADRs). Therapeutic drug monitoring (TDM) offers a personalized dosing approach that may improve drug safety and efficacy. This study aimed to evaluate the clinical and pharmacoeconomic benefits of TDM-guided dosing compared to traditional BSA-based dosing in breast cancer patients receiving docetaxel-based chemotherapy.</div></div><div><h3>Methods</h3><div>A randomized controlled study was conducted at the Department of Breast Surgery, IPMCH, from October 2022 to July 2024. A total of 208 breast cancer patients were enrolled and randomly assigned to two groups: the BSA group (<em>n</em> = 104) and the TDM-guided pharmacokinetics (PK) group (<em>n</em> = 104). Adverse drug reactions—including hematological, gastrointestinal, skin, neurotoxic, and cardiotoxic events—were monitored and compared between groups. Liver function markers (ALT, AST, ALP) and pharmacoeconomic data (treatment-related costs) were also assessed. Statistical analyses included univariate and interaction models to evaluate the impact of dosing strategy on ADRs and costs.</div></div><div><h3>Results</h3><div>Patients in the TDM-guided PK group exhibited significantly lower levels of ALT, AST, and ALP, indicating reduced hepatic toxicity. Gastrointestinal ADRs—including nausea, diarrhea, and constipation—were less frequent and less severe in the PK group compared to the BSA group. Overall, the incidence and severity of ADRs were markedly reduced in the PK group. Pharmacoeconomic analysis demonstrated consistently lower treatment-related costs in the PK group. Both univariate and interaction analyses confirmed the clinical and economic benefits of TDM-guided dosing.</div></div><div><h3>Conclusion</h3><div>TDM-guided docetaxel dosing significantly reduced ADRs and improved cost efficiency in breast cancer chemotherapy. These findings support the implementation of TDM as a superior strategy to traditional BSA-based dosing, with potential to enhance both patient safety and healthcare resource utilization.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"217 ","pages":"Article 107407"},"PeriodicalIF":4.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145741614","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":"Dual-functionalized mesoporous silica nanoparticles for topical axitinib delivery to the posterior eye segment","authors":"Li Xu ,&nbsp;Zih-An Chen ,&nbsp;Cheng-Hsun Wu ,&nbsp;Yi-Ping Chen ,&nbsp;Si-Han Wu ,&nbsp;Chung-Yuan Mou ,&nbsp;Ching-Li Tseng ,&nbsp;Yueh Chien ,&nbsp;Hardy Wai-Hong Chan ,&nbsp;Tien-Chun Yang ,&nbsp;Shih-Hwa Chiou","doi":"10.1016/j.ejps.2025.107398","DOIUrl":"10.1016/j.ejps.2025.107398","url":null,"abstract":"<div><div>Topical drug delivery to the posterior eye segment remains a significant challenge due to ocular anatomical barriers, particularly in diseases such as wet age-related macular degeneration (AMD), where treatment typically relies on frequent intravitreal (IVT) injections of anti-angiogenic agents. In this study, we present a non-invasive eye drop formulation of axitinib (AXT), a potent vascular endothelial growth factor receptor (VEGFR) inhibitor, encapsulated within 25-nm dual-functionalized mesoporous silica nanoparticles (AXT@dual-MSNs) engineered for efficient retinal delivery. The nanoparticles feature sulfonate-functionalized mesopores that enhanced AXT loading and solubilization, along with a PEGylated/quaternary ammonium-modified surface that improved colloidal stability and favored intramesopore drug confinement. Following topical administration, AXT@dual-MSNs achieved retinal accumulation via the conjunctiva-sclera-choroid pathway, effectively bypassing the corneal route. A pharmacokinetic analysis confirmed rapid, transscleral delivery of AXT with therapeutically relevant concentrations in the retina. In a laser-induced choroidal neovascularization (CNV) mouse model, a well-established surrogate for wet AMD, AXT@dual-MSN eyedrops significantly suppressed neovascular lesion formation, outperforming free-drug eyedrops and IVT AXT injection. Notably, the formulation exhibited excellent ocular tolerance, with no evidence of local toxicity or contralateral eye exposure. This work introduces a novel nanocarrier system capable of overcoming the longstanding delivery barrier to the posterior eye segment via eyedrops, offering a safe, effective, and clinically translatable alternative to IVT injections. The modular design of AXT@dual-MSNs also holds promise for expanding topical access to other hydrophobic or labile therapeutics targeting retinal diseases.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"217 ","pages":"Article 107398"},"PeriodicalIF":4.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145700086","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":"A novel microbubble delivery platform with high payload of paclitaxel upon focused ultrasound for enhanced glioblastoma treatment","authors":"Yudie Yan ,&nbsp;Kihwan Hwang ,&nbsp;Jungmin Lee ,&nbsp;Kyung Mi Nam ,&nbsp;Soyeon Shin ,&nbsp;Been Yoon ,&nbsp;Zhen Zhang ,&nbsp;Myoung-Hwan Park ,&nbsp;Chae-Yong Kim","doi":"10.1016/j.ejps.2025.107415","DOIUrl":"10.1016/j.ejps.2025.107415","url":null,"abstract":"<div><div>Effective chemotherapy for glioblastoma (GBM) is severely limited by the impermeability of the blood-brain barrier (BBB). Although paclitaxel (PTX) demonstrates potent anti-glioma activity <em>in vitro</em>, its poor BBB penetration precludes its clinical use for GBM. We developed a novel PTX-loaded microbubble (PTX@MB) platform designed for targeted drug delivery to gliomas via low-intensity focused ultrasound (LIFU). PTX@MB were fabricated using a perfluorocarbon (PFC) liquid core stabilized by F-127, and their physicochemical properties were characterized. <em>In vitro</em> anti-tumor effects were evaluated using U87MG cells in both 2D culture and 3D spheroid models. For <em>in vivo</em> assessment, an orthotopic U87MG glioma mouse model was utilized. Following intravenous administration of PTX@MB, LIFU was applied to the tumor region to induce localized drug release and transient BBB disruption. Therapeutic outcomes were evaluated by MRI, survival analysis, and histopathology. The fabricated PTX@MB were spherical, with a high drug encapsulation efficiency of 89.1 ± 0.5 %, and exhibited ultrasound-responsive drug release. <em>In vitro</em>, the combination of PTX@MB and ultrasound exposure demonstrated dose-dependent cytotoxicity and significant inhibition of U87MG spheroid growth. In the orthotopic mouse model, the PTX@MB + LIFU treatment significantly suppressed tumor progression and prolonged median survival compared to the control group. The PTX@MB + LIFU system significantly reduced tumor burden without notable systemic toxicity. This ultrasound-responsive platform enables targeted PTX delivery across the BBB and offers a promising, non-invasive strategy for site-specific chemotherapy in neuro-oncology.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"217 ","pages":"Article 107415"},"PeriodicalIF":4.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145755745","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":"Nortriptyline-targeted siRNA-loaded liposomes: Design, affinity, biodistribution, and bioactivity in a murine Herpes Simplex Virus 1 corneal infection model","authors":"Doaa Jbara-Agbaria ,&nbsp;Neethi C Thathapudi ,&nbsp;Marc Groleau ,&nbsp;Majd Agbaria ,&nbsp;Marie-Claude Robert ,&nbsp;Natalia Callai Da Silva ,&nbsp;Sebastien Talbot ,&nbsp;Janet Laganiere ,&nbsp;May Griffith ,&nbsp;Gershon Golomb","doi":"10.1016/j.ejps.2025.107388","DOIUrl":"10.1016/j.ejps.2025.107388","url":null,"abstract":"<div><div>Herpes simplex virus type 1 (HSV1) establishes latency in the trigeminal ganglia and reactivates to cause recurrent infections and severe complications, including herpes simplex keratitis (HSK), the leading cause of infectious corneal blindness in developed countries. We developed and characterized a targeted siRNA delivery system designed to suppress HSV1 by silencing the immediate-early gene ICP0, which encodes a protein essential for lytic infection and viral reactivation. To enhance neuronal accumulation, siRNA-loaded liposomes were decorated with nortriptyline (NTP), a ligand with high affinity for neuronal cells, including those in the trigeminal ganglia. The liposomes were optimized to exhibit nanoscale size, low polydispersity, neutral surface charge, high siRNA loading, spherical morphology, and long-term shelf stability. Studies in cell lines confirmed efficient internalization with good tolerability, and targeted liposomes showed enhanced binding to differentiated PC‑12 neuronal cells, competitively inhibited by free NTP, supporting their targeting specificity. Following retro-orbital administration in mice, NTP-targeted siHSV1 liposomes preferentially accumulated in the trigeminal ganglia. Antiviral efficacy was further assessed by topical application of siHSV1‑loaded liposomes within a biocompatible hydrogel in a murine HSV1 corneal perforation model of HSK. In the corneal limbus, targeted liposomes produced a significant reduction in viral load, whereas in the contralateral trigeminal ganglia, they significantly reduced viral load with a pronounced trend toward decreased ICP0 expression. These results demonstrate the feasibility of using NTP-mediated targeting ligand and support the potential of this delivery platform for treating latent HSV1, warranting further optimization for improved therapeutic efficacy.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"217 ","pages":"Article 107388"},"PeriodicalIF":4.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145631484","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}