European Journal of Pharmaceutical Sciences最新文献

{"title":"Passive microfluidic-based core-shell drug delivery: a fluid mechanics-centric review","authors":"Yasaman Mozhdehbakhsh Mofrad ,&nbsp;Sasan Asiaei","doi":"10.1016/j.ejps.2025.107366","DOIUrl":"10.1016/j.ejps.2025.107366","url":null,"abstract":"<div><div>Core-shell microparticles have gained significant attention in drug delivery systems due to their ability to encapsulate multiple compounds, provide controlled release, and enhance stability. Conventional synthesis methods often face challenges in achieving uniform particle size and shell thickness. This review summarizes passive microfluidic techniques as a precise and reproducible approach for producing core-shell microparticles. The review focuses on the microfluidic aspects of the process, with three key parameters analyzed: physical properties of the phases, flow characteristics, and microfluidic chip geometries. Previous studies on the effects of hydrodynamic parameters (including flow rate, viscosity, and interfacial tension) on droplet formation are summarized, along with analyses of how different microfluidic chip geometries optimize particle size and morphology. By compiling and analyzing data from previous studies, this review provides a comprehensive analytical framework that can aid in optimizing process parameters for generating monodisperse droplets with precise control over shell thickness and core size. This extensive review highlights the key factors influencing passive core-shell microparticle production and offers guidance for designing and developing more efficient microfluidic systems for drug delivery and other biomedical applications.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"216 ","pages":"Article 107366"},"PeriodicalIF":4.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145476787","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrating simulation and experimental validation of nutrient-limited growth in breast cancer spheroids","authors":"Celia Nieto ,&nbsp;Álvaro González-Garcinuño ,&nbsp;Eva Martín del Valle","doi":"10.1016/j.ejps.2025.107370","DOIUrl":"10.1016/j.ejps.2025.107370","url":null,"abstract":"<div><div>Multicellular tumor spheroids (MCTS) represent a relevant in vitro model for breast cancer (BC), so they are widely used to study cancer pathobiology and evaluate novel antitumor drugs. However, predictive computational tools that simulate these <em>in silico</em> models remain limited, hindering the potential for developing patient-specific therapies.</div><div>In this work, a COMSOL-based multiphysics model of HER2-positive BT-474 MCTS was developed, integrating Gompertzian growth dynamics, nutrient diffusion, uptake kinetics, and porosity evolution. The model also incorporated an expanding mesh to accurately predict diffusion phenomena. Experimental data on spheroid size, necrotic core formation, glucose consumption, and porosity were used for parameterization and validation. The developed model successfully reproduced growth dynamics, glucose uptake, and necrotic core development. Moreover, a glucose concentration threshold of ∼0.08 mM was identified as critical for necrosis. Oxygen gradients were also simulated, but prediction showed that necrotic levels were not reached.</div><div>This experimentally based computational model provides a robust platform for investigating tumor behavior under nutrient-limited conditions and may offer a valuable tool for preclinical drug evaluation.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"216 ","pages":"Article 107370"},"PeriodicalIF":4.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145480778","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 round window membrane permeability enhancers: An animal study","authors":"Jae Sang Han ,&nbsp;Ye Lin Kim ,&nbsp;Kyusun Park ,&nbsp;Ji Hyung Lim ,&nbsp;Hong-Lim Kim ,&nbsp;So Young Park ,&nbsp;Shi Nae Park","doi":"10.1016/j.ejps.2025.107256","DOIUrl":"10.1016/j.ejps.2025.107256","url":null,"abstract":"<div><div>Intratympanic (IT) delivery of dexamethasone (DEX) is widely used for treating inner ear disorders; however, its therapeutic efficacy is limited by poor permeability of the round window membrane (RWM). This study aimed to evaluate and compare the efficacy and safety of three pharmacological agents—histamine (HIS), 3% hypertonic saline (3% HS), and sodium caprate (SC)—as adjuvants for enhancing RWM permeability and improving IT-DEX delivery in a murine model. Following IT administration of each permeability enhancer followed by DEX injection, perilymph DEX concentrations were measured using ultra-high-performance liquid chromatography, and DEX receptor expression in the organ of Corti was assessed by immunofluorescence. Structural changes in the RWM were examined by transmission electron microscopy, and auditory function was evaluated using auditory brainstem response (ABR) testing. All three enhancers significantly increased perilymph DEX concentrations compared to controls, with 3% HS demonstrating the highest levels. 3% HS also induced the greatest DEX receptor expression and caused only transient RWM structural alterations without permanent damage. Despite enhanced drug delivery, no statistically significant differences in ABR threshold recovery were observed among treatment groups. These findings demonstrate that 3% HS is the most effective adjuvant among those tested for IT drug delivery, although enhanced inner ear drug penetration does not necessarily translate to improved functional recovery in this model.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"216 ","pages":"Article 107256"},"PeriodicalIF":4.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145014141","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Implantable drug delivery system improves tolerability of anti-CD40/anti-PD1 and chemotherapy in a murine model of breast cancer","authors":"Samantha J. Wade ,&nbsp;Elahe Minaei ,&nbsp;Ashleigh Hope ,&nbsp;Ross J Turner ,&nbsp;Chelsea Penney ,&nbsp;Paul A. Beavis ,&nbsp;Junyun Lai ,&nbsp;Gordon G. Wallace ,&nbsp;Sameera Ansar ,&nbsp;Naila Islam ,&nbsp;Alistair Lochhead ,&nbsp;Daniel Brungs ,&nbsp;Morteza Aghmesheh ,&nbsp;Kara L. Vine-Perrow","doi":"10.1016/j.ejps.2025.107359","DOIUrl":"10.1016/j.ejps.2025.107359","url":null,"abstract":"<div><div>Triple negative breast cancer (TNBC) is associated with the poorest prognosis among breast cancer subtypes and while immunotherapy has demonstrated some promise, its effectiveness as a monotherapy remains limited, offering only modest improvements in clinical outcomes when combined with chemotherapy. Immune checkpoint therapies, such as PD-1 inhibitors, elicit responses in a subset of patients with metastatic TNBC, and few patients experience durable effects. One reason for this limited efficacy may be due to defects in antigen presentation, as the deficiency of dendritic cells, essential for effective antigen presentation, correlates with inadequate anti-tumour immunity. To address this challenge, we report the development of a novel implantable drug delivery device that enables the localized administration of a CD40 agonist in combination with anti-PD1, doxorubicin and nanoparticle albumin–bound paclitaxel (nab-paclitaxel). CD40 agonists are a unique class of agents that activate antigen-presenting cells, including dendritic cells and B cells, and reprogram macrophages to support anti-tumour immunity. By enabling targeted delivery to the tumour site, we aimed to enhance immune priming while mitigating systemic toxicities often observed with combinations of intravenous chemo-immunotherapy. In a 4T1 murine model of TNBC, repeated systemic administration of the therapeutic combination led to fatal xenogeneic reactions, which were not observed with the localized delivery approach. Localized delivery also slowed tumour growth compared to systemic administration of the therapeutic compounds. Immune profiling further revealed that the addition of anti-CD40 agonist antibody promoted the activation of PD-1+ CD8+ <em>T</em> lymphocytes within the lymph nodes in both locally and systemically treated animals. However, the localized approach achieved equivalent or enhanced immune activation without inducing the fatal immune reactions observed with systemic dosing, suggesting that localized treatment can offer a significant therapeutic advantage. This study demonstrates that our innovative localized delivery approach has the potential to significantly improve patient outcomes by maximizing efficacy and minimizing adverse effects for this aggressive subtype of breast cancer.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"216 ","pages":"Article 107359"},"PeriodicalIF":4.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145444463","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hybrid GPP–hospital control strategy for semi-solid extrusion 3D printing of ONC201 chewable units in pediatric oncology","authors":"Stephanie Ramos ,&nbsp;Marina Vignes ,&nbsp;Philippe-Henri Secretan ,&nbsp;François-Xavier Legrand ,&nbsp;Maxime Annereau ,&nbsp;Bernard Do","doi":"10.1016/j.ejps.2025.107326","DOIUrl":"10.1016/j.ejps.2025.107326","url":null,"abstract":"<div><div>Children with central nervous system tumors often face significant barriers to age-appropriate medicines, especially when dysphagia prevents the use of conventional tablets or capsules. ONC201 (dordaviprone), a first-in-class imipridone available in France under a compassionate access program, poses additional challenges of poor solubility and chemical instability. Chewable formulations offer an attractive solution for pediatric compliance, but their development requires robust pharmaceutical and regulatory controls to ensure safety, stability, and reproducibility.</div><div>We describe a hybrid GPP–hospital control strategy for semi-solid extrusion (SSE) three-dimensional printing of ONC201 chewable units. In this model, an ONC201 hydrogel intermediate is prepared centrally in a Good Preparation Practices (GPP)-compliant unit under Quality by Design (QbD) specifications and subsequently distributed to hospital pharmacies for on-demand personalization. Patient-ready chewable units are produced locally under in-process controls (IPCs) that monitor extrusion, geometry, unit weight, disintegration, and drug content.</div><div>Formulation screening and batch characterization identified a stable ONC201 hydrogel suitable for decentralized use, with a conservative refrigerated shelf-life of 14 days. Printed chewable units demonstrated consistent quality attributes and rapid drug release, meeting pharmacopeial expectations for immediate release dosage forms.</div><div>By combining centralized QbD-controlled preparation with decentralized hospital-based personalization, this work establishes a transferable framework for safe, traceable, and patient-adapted delivery of ONC201 in pediatric oncology, complementing ongoing clinical investigations.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"216 ","pages":"Article 107326"},"PeriodicalIF":4.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145307298","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":"Comparison of in vitro lipolysis, sequential lipolysis – ex vivo permeability, and simultaneous lipolysis - in situ perfusion for exemestane-loaded lipid-based formulations","authors":"Burcu Timur ,&nbsp;Seval Olgac ,&nbsp;Yilmaz Usta ,&nbsp;Murside Ayse Demirel ,&nbsp;Zeynep Safak Teksin","doi":"10.1016/j.ejps.2025.107372","DOIUrl":"10.1016/j.ejps.2025.107372","url":null,"abstract":"&lt;div&gt;&lt;div&gt;This study aimed to investigate the in vitro lipolysis of five different self-nanoemulsifying drug delivery system (SNEDDS) formulations and to test the formulations by combining the in vitro lipolysis with ex vivo permeability and in situ perfusion methods as permeation steps, and then to compare the methods. Exemestane (EXE) was selected as the model drug due to its low solubility and nonionic nature. Four SNEDDS formulations, differing from the main formulation (MCF&lt;sub&gt;K40&lt;/sub&gt;) in terms of cosolvent content (MCF&lt;sub&gt;CoS&lt;/sub&gt;), oil type (LCF), digestible surfactant content (MCF&lt;sub&gt;T80&lt;/sub&gt;), and oil amount (MCF&lt;sub&gt;I988&lt;/sub&gt;), were prepared to contain equal EXE amounts and characterized. Firstly, a classical (without permeation step) in vitro lipolysis study was conducted for SNEDDS formulations and reference product. During lipolysis, higher drug precipitation, in other words, free drug fraction, was observed in formulations containing digestible excipients (MCF&lt;sub&gt;T80&lt;/sub&gt; and MCF&lt;sub&gt;I988&lt;/sub&gt;) and reference. Subsequently, a sequential lipolysis – ex vivo permeability study was conducted for SNEDDS formulations and reference using a vertical Franz diffusion cell with porcine intestinal tissue with samples taken from lipolysis medium at different times (0., 15., and 60. min). The similar permeated EXE% and the area under the permeated EXE% − time curve values ​​were obtained for all SNEDDS regardless of the free drug fraction. The different stages of SNEDDS lipolysis did not affect EXE permeability. Subsequently, the lipolysis study was coupled with an in situ perfusion study that would allow simultaneous lipolysis and permeation. MCF&lt;sub&gt;K40&lt;/sub&gt; and MCF&lt;sub&gt;I988&lt;/sub&gt;, which were selected due to their differences in lipolysis extent and free drug fraction, and EXE solution were examined with this method. Despite the in vitro formulation differences, the two SNEDDS formulations showed similar effective permeability coefficient (&lt;em&gt;P&lt;sub&gt;eff&lt;/sub&gt;&lt;/em&gt;) values ​​to each other and those of the EXE solution. It was shown that EXE’s bioavailability problem due to low solubility could be overcome with SNEDDS formulations. Furthermore, the sequential lipolysis – ex vivo permeability study was found to capture the results of the simultaneous lipolysis - in situ perfusion study, which more closely simulates in vivo. This was attributed to the use of intestinal tissue as a permeation barrier, which allowed the diffusion of colloidal-sized micelles, vesicles, and lipid digestion products in the ex vivo study. Since the in situ perfusion method is not suitable for screening of lipid-based formulations (LBF), the first data for using in vitro lipolysis combined with Franz diffusion cell with intestinal tissue instead were presented in this study. Combining lipolysis with the permeation step is necessary for the evaluation of LBF. Although both methods used in this study are promising, further evaluations are needed regarding horizo","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"216 ","pages":"Article 107372"},"PeriodicalIF":4.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145488223","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":"Development of a 3D printed multiple unit particle system (MUPS) containing metoprolol succinate","authors":"Lee Roy Oldfield ,&nbsp;Björn Fischer ,&nbsp;Tobias Auel ,&nbsp;Anne Seidlitz","doi":"10.1016/j.ejps.2025.107380","DOIUrl":"10.1016/j.ejps.2025.107380","url":null,"abstract":"<div><div>This study presents the development and characterisation of dual extrusion 3D printed multiple unit particle system (MUPS) tablets incorporating metoprolol succinate. Pharmaceutical-grade filaments were prepared via hot-melt extrusion, comprising a drug loaded sustained release formulation of Eudragit® RL PO, and a rapidly disintegrating tablet shell formulation based on Kollicoat® IR. The use of fused filament fabrication enabled the integration of drug-loaded cylindrical particles within the tablet shell. Comprehensive morphological and structural analyses, including scanning electron microscopy, X-ray micro-computed tomography, and digital microscopy, confirmed uniform particle geometry and distribution. The manufactured tablets met European Pharmacopoeia (Ph. Eur.) specifications for mass uniformity. Disintegration testing demonstrated complete disintegration of the tablet shell within 15 min. X-ray powder diffraction indicated the active pharmaceutical ingredient (API) was present in an amorphous state post-processing. High-performance liquid chromatography analysis revealed thermal degradation during 3D printing, with a reduction in API content from 97.8 % in the extruded filament to 65.9 % in the printed MUPS tablets. A linear correlation between the number of printed particle layers and the final drug content was shown, supporting the concept of dose individualisation. In vitro dissolution testing showed that 80 % of the incorporated API was released within 105 to 150 min. The findings confirm the feasibility of producing API-3D-MUPS tablets using pharmaceutical-grade materials, while also identifying critical product defects, formulation and process parameters such as thermal instability of the API or particle agglomeration - that require further optimisation of formulation and process parameters to enable broader application in personalised drug delivery.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"216 ","pages":"Article 107380"},"PeriodicalIF":4.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145530312","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":"An integrated deep learning model accelerates luciferase based high throughput drug screening","authors":"Xiaonan Zhang ,&nbsp;Xinxin Zhang ,&nbsp;Shuang Wang ,&nbsp;Qiaoling Song ,&nbsp;Hang Xu ,&nbsp;Minghui Zhang ,&nbsp;Xudong Zhang ,&nbsp;Hao Xie ,&nbsp;Jing Xu ,&nbsp;Ying Zhang ,&nbsp;Jiayi Yin ,&nbsp;Qingyu Tian ,&nbsp;Xiaochun Liu ,&nbsp;Yue Zhong ,&nbsp;Wei He ,&nbsp;Changming Dong ,&nbsp;Mingming Zhou ,&nbsp;Wenting Wang ,&nbsp;Xiaohan Xu ,&nbsp;Lewei Wang ,&nbsp;Chunhua Lin","doi":"10.1016/j.ejps.2025.107315","DOIUrl":"10.1016/j.ejps.2025.107315","url":null,"abstract":"<div><div>High-throughput screening presents clear advantages in accelerating drug development efficiency, but also faces challenges such as high costs, time-consuming processes, and labor-intensive procedures. To address these issues, we developed an integrated deep learning model to find patterns between the structural and molecular characteristics of compounds and our well-established luciferase based HTS values. We utilized about 100,000 HTS values from 18,840 compounds in five luciferase assays including STAT&amp;NFκB system, PPAR system, P53 system, WNT system, and HIF system. Following AI-prediction for putative targeted hit compounds from 8713 compounds, the <em>in vitro</em> and <em>in vivo</em> experimental validation was performed, and drug candidates (inhibitors or activators) with anti-inflammatory, anti-tumor or anti-metabolic syndrome were identified. T4230 exerts its anti-inflammatory effects by inhibiting the expression of inflammatory factors. The classification performance of the compounds after the joint screening exceeded the performance of the respective sub-models when screened independently and the screening accuracy and efficiency improved 7.08 to 32.04-fold across these five systems compared to our conventional HTS. The integrated AI-conducted HTS model we have developed could reduce R&amp;D costs and accelerate the drug development process, making it a valuable referential pipeline for the artificial intelligence accelerated specific signaling pathway-luciferase HTS.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"216 ","pages":"Article 107315"},"PeriodicalIF":4.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145257652","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":"Effects of Tetrahydrouridine Pre-dosing on Absorption, Metabolism, and Excretion of Decitabine in the Mouse","authors":"Hans Helleberg,&nbsp;Inga Bjørnsdottir,&nbsp;Hanne Kjær Offenberg","doi":"10.1016/j.ejps.2025.107353","DOIUrl":"10.1016/j.ejps.2025.107353","url":null,"abstract":"<div><h3>Background</h3><div>Elevated fetal hemoglobin (HbF) levels improve outcomes in sickle cell disease (SCD). decitabine (DEC), a DNA methyltransferase 1 inhibitor, reactivates silenced HbF but is rapidly degraded by cytidine deaminase (CDA). Co-administered tetrahydrouridine (THU) inhibits CDA, enhancing DEC bioavailability. NDec, a novel oral, fixed-dose combination of DEC and THU, has been developed as treatment for people with SCD. NDec is currently undergoing clinical evaluation, beginning with the Phase II ASCENT1 study (NCT05405114).</div></div><div><h3>Objective</h3><div>This study aimed to evaluate the impact of THU pre-dosing on the pharmacokinetics (PK), metabolism, and excretion profile of DEC in mice.</div></div><div><h3>Methods</h3><div>Mice were orally administered with either radiolabeled DEC ([¹⁴C]-DEC; 1 mg/kg) or with two different doses of THU (10 and 170 mg/kg) one hour before a fixed-dose of [¹⁴C]-DEC (0.4 mg/kg). Liquid scintillation counting (LSC), high-performance liquid chromatography (HPLC), LC-mass spectrometry (LC-MS), and LC-radioactivity monitor-MS (LC-RAM-MS) analyses were used to detect the presence of [¹⁴C]-DEC and its metabolites in plasma and urine at different time points after dosing.</div></div><div><h3>Results</h3><div>DEC metabolism occurs by either deamination (CDA metabolism) or by competitive hydrolysis and oxidation pathways (non-CDA metabolism), generating six DEC metabolites. THU pre-treatment increased DEC plasma exposure and shifted the metabolite profile towards non-CDA mediated metabolism. Finally, DEC and its metabolites were primarily excreted via the urinary tract, independently of THU pre-dosing.</div></div><div><h3>Conclusion</h3><div>These findings provide crucial insights into DEC metabolism, highlighting the impact of THU pre-treatment on DEC plasma exposure, metabolism, and excretion.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"216 ","pages":"Article 107353"},"PeriodicalIF":4.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145400309","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 dual-strategy nanocomposite hydrogel platform of nanosuspensions and deformable liposomes for enhanced curcumin delivery against skin cancer cells","authors":"Khin Cho Aye ,&nbsp;Supusson Pengnam ,&nbsp;Boonnada Pamornpathomkul ,&nbsp;Thapakorn Charoenying ,&nbsp;Prasopchai Patrojanasophon ,&nbsp;Praneet Opanasopit ,&nbsp;Chaiyakarn Pornpitchanarong","doi":"10.1016/j.ejps.2025.107373","DOIUrl":"10.1016/j.ejps.2025.107373","url":null,"abstract":"<div><div>Patient outcomes in skin cancer are compromised by invasive treatments, demanding a paradigm shift toward effective, non-invasive strategies. This study aimed to develop dual-strategy nanocomposite hydrogel platforms for enhanced, localized delivery of curcumin against skin cancer cells. Two distinct nanocarriers, curcumin nanosuspensions (CUR-Ns) and curcumin liposomes (CUR-Lip), were engineered and embedded within a bioadhesive Gantrez™/gelatin hydrogel. Anticancer activity, cellular uptake, and apoptosis induction were assessed in A431 skin cancer cell line. Nanocomposite hydrogels were fabricated by EDC/NHS crosslinking, with nanocurcumin pre-mixed in gelatin to ensure uniform dispersion. <em>Ex vivo</em> skin permeation was evaluated using Franz diffusion cells with neonatal porcine skin. Both formulations demonstrated potent anticancer activity against A431 cells, with CUR-Lip (IC₅₀ = 9.32 µg/mL) and CUR-Ns (IC₅₀ = 13.43 µg/mL) dramatically outperforming free CUR (IC₅₀ = 44.73 µg/mL) while maintaining excellent biocompatibility. Physicochemical characterizations of the hydrogel demonstrated high moisture content, fluid absorbency, and adequate mechanical strength. These favorable properties facilitated effective delivery. Crucially, the nanocarriers displayed unique therapeutic kinetics. CUR-Ns provided a rapid onset of action, characterized by faster initial skin permeation. In contrast, CUR-Lip offered superior sustained efficacy, showing greater cytotoxicity, and achieving significantly higher cumulative skin deposition, with a transdermal flux of 105.52 ng/cm²/h. The hydrogel platform successfully preserved these distinct permeation profiles, confirming its utility as a versatile delivery vehicle. This dual-strategy approach enables tailored curcumin delivery offering either rapid or sustained release and represented a significant advancement in developing non-invasive therapies for skin cancer.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"216 ","pages":"Article 107373"},"PeriodicalIF":4.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145488149","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}