European Journal of Pharmaceutics and Biopharmaceutics最新文献

{"title":"Inhalable nanocapsules for lung delivery of Pirfenidone and Bacterioruberin: Modulating macrophages to target pulmonary fibrosis.","authors":"Micaela Ailén Juncal, Ezequiel Nicolás Caputo, Patricia Carolina Rivas Rojas, María José Morilla, Eder Lilia Romero, Leticia Herminia Higa, María Julia Altube","doi":"10.1016/j.ejpb.2025.114893","DOIUrl":"https://doi.org/10.1016/j.ejpb.2025.114893","url":null,"abstract":"<p><p>In this work, we developed an inhalable polymeric-lipid nanocapsule formulation with mucus-penetrating properties to co-encapsulate Pirfenidone (Pfd) and the carotenoid Bacterioruberin (BR), aiming to enhance anti-inflammatory, antioxidant, and antifibrotic effects by modulating pulmonary macrophage activity. Nanocapsules (pNC-BR-Pfd) were prepared via double emulsion technique, exhibiting a Z average of 171 ± 47 nm and a Z potential of -45 ± 5 mV. Transmission electron microscopy and small angle X-ray scattering analyses revealed predominant particle sizes around 50 nm. Raman spectroscopy confirmed the successful co-encapsulation of Pfd and BR. Pfd release assay showed that 18 ± 9 % of Pfd was encapsulated, displaying a biphasic release pattern: an initial burst attributed to surface-adsorbed drug, followed by sustained release from the lipidic core. pNC-BR-Pfd preserved their physicochemical properties after nebulization using a vibrating mesh nebulizer. Surface PEGylation significantly enhanced penetration through artificial lung mucus, both in a Transwell assay and in mucus-covered A549 and THP-1 cell cultures. In LPS-activated THP-1 macrophages, pNC-BR-Pfd reduced intracellular reactive oxygen species and suppressed IL-6 and TNF-α levels by approximately 3-fold at 10 μg/mL Pfd and 0.64 μg/mL BR. In contrast, free Pfd only partially inhibited IL-6 and had no effect on TNF-α. Conditioned media from LPS-activated THP-1 treated with pNC-BR-Pfd also suppressed MRC-5 fibroblast matrix metalloproteinases (MMPs) and hydroxyproline release, and significantly inhibited cell migration. While free Pfd reduced MMPs and hydroxyproline levels, but did not alter fibroblast migration. Altogether, these results demonstrate that pNC-BR-Pfd is a technically stable and pharmacologically enhanced inhalable formulation with promising anti-inflammatory, antioxidant, antifibrotic, and mucus-penetrating properties.</p>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":" ","pages":"114893"},"PeriodicalIF":4.3,"publicationDate":"2025-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145291437","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":"Tuna Collagen-Based hydrogels for the targeted delivery of BET inhibitors and BET-PROTACs in breast cancer therapy.","authors":"Irene Sevilla-Carrillo, Carolina Hermida-Merino, Inmaculada Posadas, Martin Kreuzer, María Del Mar Noblejas-López, Alberto Ocaña, Jesús Valcárcel, Daniel Hermida-Merino, Manuel M Piñeiro, Carlos Alonso-Moreno, Iván Bravo","doi":"10.1016/j.ejpb.2025.114898","DOIUrl":"https://doi.org/10.1016/j.ejpb.2025.114898","url":null,"abstract":"<p><p>Targeted protein degradation (TPD) strategies, including BET inhibitors and PROTACs, offer a promising approach for cancer therapy by selectively degrading disease-relevant proteins. However, their clinical translation is hindered by poor solubility, potential systemic toxicity, and suboptimal delivery. Here, we evaluate the feasibility of natural tuna collagen-based hydrogels as biocompatible and biodegradable carriers for localized delivery of the BET inhibitor JQ1 and its PROTAC derivative MZ1 in breast cancer. Hydrogel formulations were systematically optimized by analyzing drug encapsulation, internal fiber structure, and drug-matrix interactions, which influenced release kinetics and administration pathways. Physicochemical characterization confirmed collagen structural integrity, injectability, and mechanical stability. In vitro studies in three breast cancer cell lines showed that hydrogel-encapsulated drugs retained therapeutic efficacy and effectively inhibited migration. Cell cycle arrest and apoptosis assays, together with Synchrotron FTIR microspectroscopy, confirmed preservation of the drugs' mechanisms of action. To our knowledge, this is the first study integrating JQ1 and MZ1 into a natural gelatin-based hydrogel system for localized cancer therapy, providing a foundation for in vivo evaluation and potential applications in advanced drug delivery, tissue engineering, and precision medicine.</p>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":" ","pages":"114898"},"PeriodicalIF":4.3,"publicationDate":"2025-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145285757","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":"Tungsten residues in prefilled syringes promote monoclonal antibody aggregation and charge heterogeneity.","authors":"Chao-Yang Du, Min Zou, Zi-Ting Xu, Wei Zhao, Miao Chen, Wei-Jie Fang","doi":"10.1016/j.ejpb.2025.114900","DOIUrl":"https://doi.org/10.1016/j.ejpb.2025.114900","url":null,"abstract":"<p><p>Monoclonal antibodies (mAbs) are pivotal therapeutics; however, their stability during production and storage remains a critical challenge, particularly in prefilled syringes (PFS), where tungsten residues from manufacturing can compromise quality. This study systematically evaluates the effect of tungsten-derived from syringe needle pin extracts and commercial tungsten salts (sodium tungstate, sodium metatungstate)-on the stability of three therapeutic mAbs under accelerated conditions (40 °C, light). Using a multi-analytical approach (size-exclusion chromatography (SEC), capillary electrophoresis-sodium dodecyl sulfate (CE-SDS), light obscuration (LO), and ion exchange chromatography (IEC)), we demonstrate that tungsten pin extracts induce markedly more aggregation, fragmentation, and subvisible particle (SbVP) formation than commercial salts (a 14-fold increase in aggregates for mAb-2 at 100 ppm), with concomitant light further worsening these outcomes. We demonstrate, for the first time, that tungsten-driven degradation induced destabilization to colloidal instability (reduced T_agg) without affecting conformational stability (T_m), and is mediated by deamidation-induced acidic variants. Computational modeling suggests that mAb-2's heightened sensitivity might correlate with solvent-exposed asparagine residues. Collectively, our data highlight the imperative for tight tungsten control during PFS manufacture and antibody-specific stability assessments to mitigate risks to product quality.</p>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":" ","pages":"114900"},"PeriodicalIF":4.3,"publicationDate":"2025-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145285762","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":"Thermal analysis of magnetic nanoparticles in laryngeal cancer hyperthermia using computational simulation.","authors":"Kazhal Moetamedi, Mohammad Hossein Tavakoli, Zahra Keshtpour Amlashi, Safoora Nikzad","doi":"10.1016/j.ejpb.2025.114895","DOIUrl":"https://doi.org/10.1016/j.ejpb.2025.114895","url":null,"abstract":"<p><p>Hyperthermia is a cancer treatment method that applies controlled heat to target and destroy cancer cells. Hyperthermia raises tumor temperatures to 42-46 °C, selectively damaging cancer cells while sparing healthy tissues. In this study, the potential of Fe₃O₄ magnetic nanoparticles for hyperthermic treatment is explored through computational simulations. When exposed to an external alternating magnetic field, these nanoparticles generate localized heat, effectively elevating the temperature of the tumor region. Simulations were conducted during three distinct phases of breathing (inhalation, exhalation, and breath-hold) to evaluate their influence on heat distribution and temperature changes in both cancerous and healthy tissues. The results show that during the breath-hold phase, heat is primarily transferred to the air within the larynx, reducing the thermal effect on adjacent muscle tissues. In contrast, during the inhalation and exhalation phases, significant heat transfer occurs to the surrounding tissues, resulting in more pronounced temperature increases. These findings provide valuable insights for optimizing hyperthermic treatment protocols and suggest that magnetic nanoparticle-based hyperthermia may offer enhanced efficacy and safety for the treatment of laryngeal cancer.</p>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":" ","pages":"114895"},"PeriodicalIF":4.3,"publicationDate":"2025-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145285776","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":"Recent advances in peptide-based self-assembled and metal coordinated nanocarriers for targeted cancer drug delivery.","authors":"Vijay Bhooshan Kumar","doi":"10.1016/j.ejpb.2025.114897","DOIUrl":"https://doi.org/10.1016/j.ejpb.2025.114897","url":null,"abstract":"<p><p>Despite significant progress in anti-cancer therapies, major challenges persist, such as cytotoxicity, drug resistance, and lack of specificity toward tumour tissues. In recent years, peptide self-assembly has emerged as a powerful strategy in biomedical and cancer research for creating functional nanomaterials with enhanced therapeutic potential. A wide range of self-assembled peptide-based drug delivery systems has been developed for cancer treatment, offering improved efficacy and selectivity of pharmaceutical agents while minimizing toxicity to healthy tissues. Self-assembled peptide nanostructures exhibit excellent versatility, capable of encapsulating both hydrophobic and hydrophilic drugs, and can be engineered to release therapeutic agents at disease sites by incorporating stimuli-responsive elements. This review highlights recent advancements in the design and application of self-assembled peptide nanomaterials, based on both linear and cyclic peptides, as well as the role of metal coordination in enhancing drug delivery performance. We describe the synthesis and functionality of metal-coordinated peptide assemblies, which not only enhance stability and responsiveness but also address existing limitations in self-assembly peptide-based drug delivery, particularly in the context of triggered or site-specific release of anticancer therapeutics. Through this review, we aim to provide a comprehensive outline of recent strategies and innovations in peptide self-assembly for targeted cancer therapy, with a particular emphasis on overcoming current therapeutic challenges.</p>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":" ","pages":"114897"},"PeriodicalIF":4.3,"publicationDate":"2025-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145285800","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 pivotal, dermal, in-vivo bioequivalence study performed by confocal Raman spectroscopy (CRS).","authors":"J Link, C Heusel, D J Lunter","doi":"10.1016/j.ejpb.2025.114891","DOIUrl":"https://doi.org/10.1016/j.ejpb.2025.114891","url":null,"abstract":"<p><p>The EMA guideline on quality and equivalence of locally applied, locally acting cutaneous products, endorses the use of the stratum corneum (SC) sampling technique (Tape Stripping, TS) in lieu of an expensive and resource-intensive clinical endpoint study. However, alternative methods, like CRS are not yet approved. As we have already shown the correlation of TS and CRS results, we consider non-invasive CRS with its microscale resolution for fully quantifiable API data and its ease of use, as the superior method for future dermal bioequivalence studies for products with Raman-active drug substances. To provide pivotal data and demonstrate the suitability CRS for dermal bioequivalence assessment, we conducted an in-vivo study using four formulations containing salicylic acid(SA). The study design included a reference, a test, and a control formulation to validate discriminatory power. CRS measurements were performed in 12healthy volunteers at two defined time points - 1 h (uptake, that is in diffusional steady-state) and 4 h after product removal (clearance) - using a 785 nm laser to acquire SC penetration profiles down to a depth of 15 µm. We could demonstrate that the penetration data meet all EMA bioequivalence requirements. Thus, the supposedly bioequivalent products were confirmed to be bioequivalent, as their 90 % confidence intervals (CIs) fell entirely within the acceptance range of 80.00---125.00 %, in accordance with the average bioequivalence (ABE) approach. As this was, to our knowledge, the first dermal, in-vivo bioequivalence study conducted with the advantageous CRS method, fully following the recommendations of the EMA guideline. The pivotal data obtained thus shows the suitability of the CRS method. This should help with its establishment as a means to obtain bioequivalence data, also with reference to recognition in a subsequent guideline update.</p>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":" ","pages":"114891"},"PeriodicalIF":4.3,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145279264","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":"Corrigendum to: Film-forming system of optimized tacrolimus-loaded nanostructured lipid carriers for effective topical treatment of atopic dermatitis (European Journal of Pharmaceutics and Biopharmaceutics, volume 216, article number 114871).","authors":"Jin Sil Kang, Young-Guk Na, Minki Jin, Gabsik Yang, Dong-Sung Lee, Jong-Suep Baek, Hong-Ki Lee, Cheong-Weon Cho","doi":"10.1016/j.ejpb.2025.114899","DOIUrl":"https://doi.org/10.1016/j.ejpb.2025.114899","url":null,"abstract":"","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":" ","pages":"114899"},"PeriodicalIF":4.3,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145279238","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 deep dive into spin-labeled polysorbate's interaction with therapeutic antibody using 2D NMR, EPR and MD simulations.","authors":"Blaž Lebar, Maria Orehova, Boštjan Japelj, Ernest Šprager, Rok Podlipec, Tilen Knaflič, Iztok Urbančič, Benjamin Knez, Mitja Zidar, Jure Cerar, Janez Mravljak, Aleš Žula, Denis Arčon, Janez Plavec, Stane Pajk","doi":"10.1016/j.ejpb.2025.114892","DOIUrl":"https://doi.org/10.1016/j.ejpb.2025.114892","url":null,"abstract":"<p><p>Polysorbates (PS) are widely used surfactants in biopharmaceutical formulations playing a crucial role in protecting proteins against mechanical stress and interface-induced damage. However, their susceptibility to degradation can compromise their function and lead to particle formation. Recent studies suggest that monoclonal antibodies (mAbs) may mitigate PS degradation catalyzed by histidine chloride buffer, indicating the presence of protein-PS interactions. In this study, we investigated these interactions using NMR, starting with ¹H T₂ CPMG filter experiments and methyl fingerprinting, which failed to detect interactions. To enhance sensitivity, we synthesized spin-labeled PS (SLPS), enabling paramagnetic relaxation enhancement (PRE) NMR experiments, specifically amide fingerprinting, which successfully revealed interactions. Complementary electron paramagnetic resonance (EPR) measurements of SLPS and mAb also detected interactions, but only in the presence of sucrose, underscoring their weak and transient nature. Additionally, molecular dynamics simulations identified potential interaction hotspots on the antibody structure, providing mechanistic insights into these interactions.</p>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":" ","pages":"114892"},"PeriodicalIF":4.3,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145274249","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 SpyCatcher-assembled mannosylated nanovaccine elicits potent and cross-protective immunity against monkeypox virus.","authors":"Wenying Yan, Lijuan Shen, Jinming Qi, Weili Yu, Tao Hu","doi":"10.1016/j.ejpb.2025.114878","DOIUrl":"https://doi.org/10.1016/j.ejpb.2025.114878","url":null,"abstract":"<p><p>Monkeypox (mpox), caused by the monkeypox virus (MPXV), is a zoonotic disease of global public health concern. Current live-attenuated vaccines suffer from safety concerns and unsatisfactory protection effectiveness. To address these limitations, a protein-based nanovaccine (Ag-M-Spy) was developed to deal with mpox for its high effectiveness and favorable safety profile, incorporating three critical MPXV-derived antigens (A29L, A35R, M1R). Mannose acted as the adjuvant via mannose receptor-mediated endocytosis. Ag-M-Spy was constructed by conjugation of mannose-functionalized antigens with SpyCatcher nanoparticles via the SpyTag-SpyCatcher system. BALB/c mice were immunized intramuscularly on days 0, 14, and 28. Ag-M-Spy evoked a strong antigen-specific antibody response. In addition, Ag-M-Spy induced high levels of splenic Th1- and Th2-type cytokines. Moreover, Ag-M-Spy stimulated robust antigen-specific CD4⁺ and CD8⁺ T cell response, generated durable memory cells, activated T and B cells, enhanced cytotoxic T lymphocyte activity, and promoted dendritic cell maturation. Ag-M-Spy did not render apparent liver, kidney, or heart toxicity to mice. Moreover, it conferred in vivo protective immunity against lethal ectromelia virus challenge in BALB/c mice. In summary, Ag-M-Spy elicited robust, durable humoral and cellular immunity with favorable safety, representing a promising vaccine candidate against life-threatening mpox.</p>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":" ","pages":"114878"},"PeriodicalIF":4.3,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145274206","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 application of a novel tracer system for the evaluation of temperature exposure of lipid nanoparticles in spray drying and dual centrifugation","authors":"Isabelle Klein,&nbsp;Denise Steiner","doi":"10.1016/j.ejpb.2025.114889","DOIUrl":"10.1016/j.ejpb.2025.114889","url":null,"abstract":"<div><div>In recent years, the development of nanocarriers and nanoscale drug delivery systems has become increasingly important, with temperature-intensive processes being an essential part of their preparation and following process steps.</div><div>This study introduced a novel nanoparticular tracer system to track the highest temperatures to which the particles are exposed to during processing by exploiting the monotropic polymorphism of triglycerides. These nanoparticulate systems enabled an estimation of the temperature exposure of formulations in processes that are otherwise inaccessible or very difficult to access. Two tracer systems were developed using the solid lipids tristearin and tripalmitin, with distinct melting temperatures, and applied for the high-energy processes of spray drying and dual centrifugation. In addition, the experiments provided insights into the effect of stabilizers on triglyceride modifications. It was shown that during spray drying, the highest temperature exposure of the nanoparticles during the process was 4.1 °C and 6.6 °C for tristearin and tripalmitin, respectively, above the outlet air temperature of the spray dryer. In addition, the tristearin tracer system was used to investigate the temperature exposure during dual centrifugation, which indicated that with increasing process time of up to 480 min, all particles were progressively exposed to temperatures above their melting temperature.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"217 ","pages":"Article 114889"},"PeriodicalIF":4.3,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145250539","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}