European Journal of Pharmaceutics and Biopharmaceutics最新文献

{"title":"Autophagy-mediated amplification of ferroptosis via a curcumin-loaded metal-enzyme nanoplatform for synergistic tumor therapy.","authors":"Chenshuo Wang, Zhenzhen Ma, Mengyu Liu, Mengyu Du, Hanchun Yao","doi":"10.1016/j.ejpb.2026.115233","DOIUrl":"https://doi.org/10.1016/j.ejpb.2026.115233","url":null,"abstract":"<p><p>Ferroptosis is an iron-mediated cell death process driven by lipid peroxidation, yet its antitumor potential is often counteracted by the limited endogenous H₂O₂ content, the strict catalytic conditions required for the Fenton reaction, and protective autophagy. Notably, sustained autophagy drives ferritin degradation and iron release, thereby amplifying ferroptotic signaling. To exploit this mechanism, we designed a CD44-targeted nanoplatform, Cur@MG@HA, using hyaluronic acid for tumor-specific delivery. The system co-delivers glucose oxidase (GOx) and curcumin (Cur) within a Fe-Cu MOF. Following cellular uptake, GOx catalyzes the oxidation of intratumoral glucose to produce gluconic acid and H₂O₂. The acidic microenvironment promotes the Fe/Cu-mediated Fenton reaction, converting H₂O₂ into OH and initiating ferroptosis. The resulting oxidative stress induces autophagy, a process further potentiated by Cur. Enhanced autophagy accelerates ferritin degradation, thereby elevating labile iron levels and establishing a self-reinforcing cycle that amplifies lipid peroxidation, culminating in ferroptotic cell death. In vitro and in vivo experiments demonstrate that the self-reinforcing cycle between autophagy and ferroptosis significantly enhances tumor suppression. This study provides a mechanistic basis for synergistic therapy through redox-metabolic modulation and suggests that targeting iron-autophagy crosstalk with nanomaterials represents a promising strategy for cancer treatment.</p>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":" ","pages":"115233"},"PeriodicalIF":5.0,"publicationDate":"2026-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148896648","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PBPK model of carbamazepine and its metabolite for bioequivalence assessment: prioritizing early exposure and single-dose study designs.","authors":"Javier Zarzoso-Foj, Marina Cuquerella-Gilabert, Javier Reig-López, Víctor Mangas-Sanjuán, Alfredo García-Arieta","doi":"10.1016/j.ejpb.2026.115232","DOIUrl":"https://doi.org/10.1016/j.ejpb.2026.115232","url":null,"abstract":"<p><p>A physiologically based pharmacokinetic (PBPK) model for carbamazepine (CBZ) was calibrated against an intravenous clinical dataset. Absorption was characterised using the Advanced Dissolution, Absorption and Metabolism (ADAM) model coupled to the diffusion layer model and a particle population balance framework, incorporating formulation-specific particle size distributions. Model verification was performed against 36 clinical datasets spanning single-dose (SD), and multiple-dose (MD) oral administrations across multiple dosage forms. The model was benchmarked against a published CBZ PBPK model (Yin et al., 2024) and further verified through five drug-drug interaction scenarios involving cytochrome P450 modulation. Virtual bioequivalence trials (2 × 2 crossover, n = 24, 100 replicates) were conducted for oral suspensions and immediate-release tablets to compare SD and MD discriminatory power, and to evaluate partial AUC from 0 to 2 h (pAUC_0-2h) against conventional bioequivalence metrics. The model matched or outperformed Yin et al. across all scenarios. SD designs consistently demonstrated superior discriminatory power over MD designs (contradicting the proposal that MD studies are more discriminating for autoinducing CBZ); despite autoinduction progressively increasing apparent clearance, formulation-related differences in absorption were attenuated at steady state. pAUC_0-2h showed higher sensitivity than C_max for detecting absorption rate differences. These findings support SD study designs for CBZ bioequivalence assessment and identify pAUC_0-2h as a clinically meaningful complementary metric.</p>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":" ","pages":"115232"},"PeriodicalIF":5.0,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148879300","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rebamipide Nanosuspension Loaded In Situ Gel: A Promising Strategy to Improve Ocular Delivery and Treatment of Dry Eye Disease.","authors":"Sayali Rathod, Klaudi K Vaiphei, Akhila Reddy, Amoolya Sree, Kendre Sandhya Rani, Jayabalan Nirmal, Tamilvanan Shunmugaperumal, Sanjay K Banerjee, Swatishree Nayak, Arvind Gulbake","doi":"10.1016/j.ejpb.2026.115231","DOIUrl":"https://doi.org/10.1016/j.ejpb.2026.115231","url":null,"abstract":"<p><strong>Purpose: </strong>Rebamipide (REBA) is used in the treatment of dry eye disease (DED) and is available as Mucosta® ophthalmic suspension that is widely used in Japan. However, certain challenges such as blurred vision, less permeation due to large particle size, frequent administration because of nasolacrimal drainage, and bitter taste were observed after topical instillation. So, in this study, rebamipide nanosuspension (REBA-NS) bearing in-situ gel (REBA-NS gel) was developed for addressing the challenges as well as ease of application.</p><p><strong>Methods: </strong>REBA-NS was prepared using the acid-base neutralization method, employing HPMC as a stabilizer and optimized using the quality-by-design approach. Further characterization and evaluation of REBA-NS was carried out, and the optimized REBA-NS was loaded to gel using gellan gum, which has a property of forming an in-situ gel after contact with the simulated tear fluid. Finally, the in-vitro and in-vivo studies of the REBA-NS gel were performed.</p><p><strong>Results: </strong>REBA-NS exhibited nanosized particles (<270 nm) that may help in enhanced permeation, low polydispersity index (<0.25) with high drug content (>80%). Moreover, the REBA-NS gel exhibited mucoadhesiveness, sustained drug release, sterile nature, optimum pH (∼7.2), and osmolality (∼216 mOsm/kg) required for ocular administration, which may aid in the retention of REBA. Finally, REBA-NS gel on the DED-induced rats depicted an increased tear secretion and decreased corneal fluorescein scoring by 1.39-folds and 9.12-folds, respectively, compared to the REBA solution on day 7 of treatment.</p><p><strong>Conclusion: </strong>In a nutshell, REBA-NS gel was found to be a promising approach for treating DED.</p>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":" ","pages":"115231"},"PeriodicalIF":5.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148873476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and evaluation of a virus-like particle PEDV vaccine based on MS2 bacteriophage.","authors":"Yawen Liu, Siying Du, Shan Xu, Yigang Tong","doi":"10.1016/j.ejpb.2026.115221","DOIUrl":"https://doi.org/10.1016/j.ejpb.2026.115221","url":null,"abstract":"<p><p>Porcine epidemic diarrhea virus (PEDV) can infect pigs of all ages, causing porcine epidemic diarrhea and resulting in significant losses to the global pig farming industry. The virus causes epidemic diarrhea and represents a significant threat to the global swine industry. To enhance vaccine safety and protective efficacy, a PEDV nanoparticle vaccine (PEDV-MS2 VLP) based on MS2 bacteriophages was developed. The MS2 phage coat (MS2 VLP) self-assembles into nanoparticles within Escherichia coli. It is conjugated to the PEDV RBD antigen via the SpyTag-SpyCatcher system, forming a structure mimicking the natural virus. Subcutaneous immunization of BALB/c mice with PEDV-MS2 VLP at days 0 and 14 resulted in a 100-fold increase in neutralizing titers and robust antigen-specific IgG responses. Additionally, PEDV-MS2 VLP induced high levels of cytokines (TNF-α, IFN-γ). The vaccine showed no significant toxicity to the liver, kidneys, or heart in mice. In summary, PEDV-MS2 VLPs demonstrate excellent safety and are a novel candidate vaccine for porcine epidemic diarrhea virus.</p>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":" ","pages":"115221"},"PeriodicalIF":5.0,"publicationDate":"2026-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148850105","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A carrier-free self-assembled mangiferin hydrogel as a dual-functional oral delivery system for baicalin against acetaminophen-induced acute liver injury.","authors":"Xinyu Huang, Shouyu Zhu, Kun Feng, Xianggen Wu, Han Wang, Dexiang Xu","doi":"10.1016/j.ejpb.2026.115220","DOIUrl":"https://doi.org/10.1016/j.ejpb.2026.115220","url":null,"abstract":"<p><p>Baicalin (BAI) is a natural flavonoid with hepatoprotective potential; however, its poor aqueous solubility and low oral bioavailability limit its therapeutic efficacy. Here, a carrier-free, self-assembled mangiferin (MAN) hydrogel was developed for oral BAI delivery without additional polymeric carriers or chemical crosslinkers. The resulting BAI@MAN HG formed a porous network with favorable hydration and viscoelastic properties while retaining antioxidant activity. FTIR, Raman spectroscopy, XRD, and DSC collectively revealed altered molecular organization, reduced crystalline order, and changes in the solid-state environment of BAI following hydrogel formation, consistent with a possible noncovalent association between BAI and MAN. BAI@MAN HG enhanced the apparent solubility, gastrointestinal release, and oral absorption of BAI, resulting in greater systemic exposure than free BAI. In a preventive mouse model of acetaminophen-induced acute liver injury, oral administration of BAI@MAN HG markedly improved liver morphology, reduced hepatocellular damage, normalized serum transaminase levels, and alleviated oxidative stress and inflammation. These protective effects were accompanied by restoration of redox homeostasis and reduced hepatic levels of HMGB1, NF-κB and other inflammatory mediators. Overall, MAN functioned as both a structural gelator and a bioactive matrix, providing a promising carrier-free platform for enhancing the oral delivery and in vivo efficacy of poorly water-soluble bioactives.</p>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":" ","pages":"115220"},"PeriodicalIF":5.0,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148826559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Towards macrophage-oriented Antituberculosis therapy: nanohydrogel and liposomal delivery of rifampicin-berberine Co-nanocrystals for enhanced intracellular Antituberculosis activity.","authors":"Xiaoguo Zhang, Ping Liu, Shengwei Ji, Jingxue Liu, Shouhua Cui, Xue Hu, Zhengbin Chai, Ibrahim Oluwatobi Kehinde, Nontobeko E Mvubu, Mahmoud E S Soliman, Zhongfa Zhang","doi":"10.1016/j.ejpb.2026.115217","DOIUrl":"https://doi.org/10.1016/j.ejpb.2026.115217","url":null,"abstract":"<p><p>Tuberculosis (TB) remains a major global health threat, compounded by prolonged treatment regimens, drug toxicity, and the emergence of multidrug-resistant Mycobacterium tuberculosis strains. In this study, we present a novel therapeutic strategy integrating co-crystallization and nanocarrier engineering to enhance the intracellular delivery and antimicrobial efficacy of rifampicin and berberine. Rifampicin-Berberine (RIF-BBR) co-crystals were synthesized via solvent-assisted grinding, and their formation was confirmed through PXRD, NMR, FTIR, DSC, TGA, and TEM analyses, revealing a new crystalline phase stabilized by non-covalent interactions and improved physicochemical properties. The co-crystal was subsequently encapsulated into chitosan-based nanohydrogels and liposomes, yielding nanocarriers with high entrapment efficiencies, favorable particle sizes, and enhanced colloidal stability. In vitro drug release studies demonstrated pH-responsive and sustained release from the nanohydrogel system, while the liposomes exhibited an initial burst release suited for rapid drug availability. Antimicrobial evaluation against M. tuberculosis H37Rv showed that the nanoformulated co-crystal significantly improved inhibitory and bactericidal activity compared to free rifampicin, berberine, and the co-crystal alone, with the liposomal formulation displaying the lowest MIC and MBC values. Collectively, these findings underscore the potential of combining co-crystal engineering with nanocarrier-based delivery to overcome the limitations of conventional TB therapy. This dual strategy enhances intracellular drug accumulation, potentiates antimicrobial activity, and provides a promising foundation for developing more effective, targeted, and patient-compliant anti-tuberculosis treatments.</p>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":" ","pages":"115217"},"PeriodicalIF":5.0,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148789942","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Two-birds-one-stone, microfluidic producing DES/W microemulsions to solubilize quercetin and penetrate intestinal mucosa for enhanced oral bioavailability","authors":"Ruirui Liu,&nbsp;Xiu Yang,&nbsp;Chaoqi Huang,&nbsp;Xiaoduo Guan,&nbsp;Yixin Li,&nbsp;Gensheng Yang,&nbsp;Qingliang Yang","doi":"10.1016/j.ejpb.2026.115007","DOIUrl":"10.1016/j.ejpb.2026.115007","url":null,"abstract":"<div><div>Quercetin has antioxidant, anti-inflammatory, antibacterial, and anticancer effects. However, its therapeutic efficacy is limited by poor water solubility, low oral absorption, and limited bioavailability. In this study, a novel deep eutectic solvent (DES) in water (DES/W) microemulsion system was developed, wherein the DES was composed of DL-menthol and capric acid at a molar ratio of 7:3, to simultaneously accomplish enhanced quercetin solubilization and promoted mucosal permeation, both of which ensuring an adequate oral bioavailability and sufficient therapeutic effectiveness. Optimized DESs were used with microfluidic technology to create uniform quercetin-loaded DES/W microemulsions under the optimal formulation conditions: Tween 20 as the surfactant, a surfactant concentration of 1.37%, a continuous phase flow rate of 30.98 mL/h, and a dispersed phase flow rate of 3.15 mL/h. The results showed that the obtained microemulsions increased quercetin solubility, retention time in the intestines, and mucosal absorption, improving drug absorption and bioavailability. Pharmacokinetic studies showed that compared with free quercetin, the area under the plasma concentration–time curve (AUC_0～t) and maximum plasma concentration (C_max) of the microemulsion formulation were significantly increased, with AUC_0～t being 5.54-fold higher than that of free quercetin. Notably, the use of microfluidic technology in preparing these microemulsions considerably reduces the need for surfactants, thus enhancing the biosafety of DES-based microemulsions. Overall, the DES/W microemulsions prepared by microfluidics could effectively addresses the challenges associated with poor absorption and low bioavailability of insoluble drugs with highly monodisperse and uniform formulations.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"222 ","pages":"Article 115007"},"PeriodicalIF":4.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146112722","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Site-specific targeting in immunoliposomal nanomedicine for oncology: opportunities and limitations","authors":"Małgorzata Milczarek ,&nbsp;Patrycja Kleczkowska (-)","doi":"10.1016/j.ejpb.2026.115004","DOIUrl":"10.1016/j.ejpb.2026.115004","url":null,"abstract":"<div><div>The integration of monoclonal antibodies with liposomal nanocarriers has opened new possibilities in targeted cancer therapy. Immunoliposomes, which are liposomes surface-conjugated with antibodies or antibody fragments, offer dual specificity by combining passive targeting (via the enhanced permeability and retention effect) with active targeting of tumor-specific antigens. This design allows for increased drug accumulation in tumor tissue and reduced off-target toxicity, which are critical challenges in conventional chemotherapy.</div><div>Although no immunoliposomal therapy has yet received the FDA or EMA approval, the platform continues to evolve. Several formulations are under clinical investigation for various solid tumors, including triple-negative breast cancer, glioblastoma, and non-small cell lung cancer. For example, in a phase II study of anti-EGFR immunoliposomes loaded with doxorubicin in advanced triple-negative breast cancer (NCT02833766), the median progression-free survival was 3.5 months, with 73% of patients experiencing disease progression within the first year.</div><div>Immunoliposomes hold promise as future therapeutic agents, especially when integrated with molecular diagnostics and patient-specific targeting strategies. However, their clinical translation requires overcoming biological and technological barriers to ensure reproducible efficacy and safety. This review critically examines current progress and explores future perspectives for this emerging therapeutic strategy in precision oncology.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"222 ","pages":"Article 115004"},"PeriodicalIF":4.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146141501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A way forward for generic development of telmisartan tablets: Integrating critical material attributes and bio-predictive dissolution for target product profile","authors":"Megha Pillai,&nbsp;Ravi P. Shah,&nbsp;Pinaki Sengupta","doi":"10.1016/j.ejpb.2026.115010","DOIUrl":"10.1016/j.ejpb.2026.115010","url":null,"abstract":"<div><div>This study systematically integrated critical material attributes (CMAs) influencing drug release, focusing on factors such as particle size and excipient composition, and characterization of polymorphic form. As a model compound, a BCS class II drug Telmisartan was selected, and the methodology was evaluated using seven different formulations of Telmisartan through comprehensive analysis. The orthogonal analytical techniques, including chromatography, hot-stage microscopy, NMR spectroscopy, and dissolution testing were employed for evaluating critical quality attributes (CQAs). Systematic efforts were made to develop a biopredictive dissolution method using USP dissolution Apparatus I, II, and IV. Based on the t_max value of telmisartan, a multi-stage dissolution strategy was developed to understand the behaviour of formulation in acidic and neutral pH corresponding to the stomach and duodenum under fasting conditions. After de-formulation experiments, formulations were categorized into different buckets based on the size of API particles(d90 value of 8 ± 2 µm; 12 ± 2 µm and &gt;15 µm), the type of excipients present (functional excipient and non-functional excipients), and the micro-environmental pH of the formulations. A rank-based approach was applied to evaluate a robust framework for understanding the differences between these generic formulations. This approach not only supports comprehensive formulation development through CMA–CQA correlations, but also aligns with regulatory expectations for adopting multi-dissolution methods as <em>in vitro</em> testing in cases of formulation change requirements with a bioequivalence waiver for post-approval formulation changes.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"222 ","pages":"Article 115010"},"PeriodicalIF":4.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146124319","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances in metal–organic framework-based drug delivery system in cuproptosis-mediated cancer therapy","authors":"Haodong Ruan ,&nbsp;Yenuo Chen ,&nbsp;Junlin Qian ,&nbsp;Xiaomu Ma ,&nbsp;Yinna Xu ,&nbsp;Yijun Deng ,&nbsp;Ying Pan ,&nbsp;Aparna Kushwaha ,&nbsp;Abhinav Kumar ,&nbsp;Biao Zheng ,&nbsp;Jianqiang Liu","doi":"10.1016/j.ejpb.2026.115021","DOIUrl":"10.1016/j.ejpb.2026.115021","url":null,"abstract":"<div><div>Cancer continues to pose an immense burden on global health, ranking among the foremost causes of disease-associated mortality. Conventional diagnostic platforms for tumor biomarkers, while widely adopted, remain constrained by limited sensitivity, protracted workflows, and substantial economic costs, thereby restricting their clinical applicability. Therapeutic modalities such as chemotherapy and radiotherapy further compound the challenge, offering only modest selectivity and being accompanied by significant systemic toxicity and a high likelihood of relapse. Metal-organic frameworks (MOFs) represent a class of structurally tailorable nanomaterials composed of modular building units, featuring tunable porosity and favourable biocompatibility, which together provide an efficient platform for drug encapsulation and controlled release. Their tumour accumulation behaviour is strongly governed by key physicochemical parameters, including particle size, morphology, and surface chemistry. Pristine MOFs primarily rely on passive tumour targeting through the enhanced permeability and retention effect, whereas surface functionalization with targeting ligands can markedly improve tumor selective enrichment and cellular uptake. Consequently, the therapeutic delivery performance of MOFs must be critically assessed in relation to their specific structural design and surface engineering strategies. In parallel, the identification of cuproptosis, a mitochondria-centered copper-dependent mode of regulated cell death, has opened a distinct mechanistic avenue for oncological intervention. This process arises from the aberrant interaction of copper ions with lipoylated tricarboxylic acid cycle proteins, culminating in excessive protein acylation, destabilization of Fe–S cluster enzymes, proteotoxic stress, and mitochondrial collapse. The rapid evolution of pharmacological agents exploiting this pathway underscores its transformative therapeutic potential. This review critically consolidates recent progress at the interface of MOFs and cuproptosis, emphasizing design strategies, mechanistic insights, and therapeutic deployment, while also addressing unresolved issues in pharmacokinetics, biosafety, and translational feasibility that must be overcome for clinical realization.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"222 ","pages":"Article 115021"},"PeriodicalIF":4.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146186428","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}