European Journal of Pharmaceutics and Biopharmaceutics最新文献

{"title":"Controlled release of deferiprone using iron-responsive nanoparticles integrated with dissolving microneedle for novel alternative treatments of β-thalassemia major","authors":"Muh.Taufik Hidayat ,&nbsp;Sitti Nur Khadijah Maharani ,&nbsp;Indianty Dwi Ramadhany ,&nbsp;Nur Izzah Khairani ,&nbsp;Nur Annisa Rahman ,&nbsp;Andi Dian Permana","doi":"10.1016/j.ejpb.2025.114702","DOIUrl":"10.1016/j.ejpb.2025.114702","url":null,"abstract":"<div><div>Iron chelating agents (ICs) such as conventional deferiprone are often ineffective when exposed to normal conditions due to their uncontrolled release when treating iron overload in ß-thalassemia major (ß-TM) due to the effects of blood transfusion. Iron deficiency and gastrointestinal side effects are crucial problems that can occur. Therefore, DFP was prepared as nanoparticles (NPs) coated with an iron-responsive (IR) polymer with an average particle size of 354.70 ± 10 nm to control its release. To facilitate optimal delivery, NP-IR-DFP was integrated into a dissolving microneedle (DMN) fabricated with biodegradable and biocompatible poly(vinylpyrrolidone) and poly(vinyl alcohol) polymers. The results showed that the NP-IR-DMN provided excellent insertion and mechanical strength and dissolved quickly after application. In vitro and <em>ex-vivo</em> studies revealed the more controllable release of NP-IR-DFP after integration with the DMN (NP-IR-DMN) for up to 24 h. Most importantly, the developed formula was hemocompatible and did not irritate the skin or cause tissue damage. Furthermore, the <em>in vivo</em> pharmacokinetics were further investigated for 24 h, which revealed short concentration (C_max of 0.07 ± 0.03 μg/mL) and t_1/2 (3.66 ± 0.76 h) under normal conditions and long-term iron overload-modeling conditions with C_max (2.90 ± 0.14 μg/mL) and t_1/2 (10.13 ± 1.00 h). This approach can extend beyond oral delivery by controlling the release of DFP, which can only be released in conditions of iron overload, and has the potential to prevent iron deficiency and excess, thus increasing the efficacy of DFP in β-TM therapy.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"210 ","pages":"Article 114702"},"PeriodicalIF":4.4,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143724477","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 modern strategy for digital real-time release testing in continuous tablet manufacturing","authors":"Selma Celikovic ,&nbsp;Jakob Rehrl ,&nbsp;Rúben Martins Fraga ,&nbsp;Martin Steinberger ,&nbsp;Johannes Khinast ,&nbsp;Martin Horn ,&nbsp;Stephan Sacher","doi":"10.1016/j.ejpb.2025.114700","DOIUrl":"10.1016/j.ejpb.2025.114700","url":null,"abstract":"<div><div>The pharmaceutical industry is currently moving away from traditional approaches to quality control with off-line quality tests, limited in-line process monitoring and minimal control strategies towards more sophisticated methods. This transition addresses several critical aspects, including the reduction of ecological and economic footprints and ensuring the safety for patients and personnel. In that context, the initial step is the application of process monitoring tools, such as process analytical technology (PAT) and soft sensors, for real-time product quality assessment. This will enable real-time release testing (RTRT), which redefines conventional approaches by relying solely on the process data reported by equipment or collected from sensors to predict the product quality. However, the implementation of RTRT requires reliable material tracking algorithms, which align the process data with the product’s characteristics.</div><div>This study proposes a modern digital RTRT strategy that aligns process data collected from a state-of-the-art manufacturing line with a sophisticated process monitoring strategy for specific product quantities, i.e., single dosage units (tablets). To trace the material through the production line and align it to the collected process data, residence time distribution (RTD) models and material tracking algorithms were developed. The digital RTRT strategy was designed and demonstrated using the industrial manufacturing line ConsiGma^TM-25. The developed strategy makes full product quality information digitally available, including critical quality attributes (CQAs) and processing conditions experienced during the production. The obtained results were validated using traditionally established off-line methods.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"211 ","pages":"Article 114700"},"PeriodicalIF":4.4,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143729515","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":"Self-dispersible eutectic mixtures with fenofibrate and ibuprofen: Processability and API particle size","authors":"Peter Schlosser,&nbsp;Heike Bunjes","doi":"10.1016/j.ejpb.2025.114701","DOIUrl":"10.1016/j.ejpb.2025.114701","url":null,"abstract":"<div><div>In order to increase the dissolution rate of poorly water-soluble drugs, the preparation of eutectics is a practical way to minimize the drug particle size without the need of grinding and handling of poorly flowing powders. The use of solid self-dispersible excipients as a component of the eutectic may further enhance the drug dissolution rate. In the current study, phase diagrams of eutectic mixtures of polyethylene glycol stearates and polyethylene glycol stearyl ethers differing in their polyethylene glycol chain lengths and two model drugs were established. Their processability and disintegration properties were investigated. Moreover, the resulting drug particle sizes in the eutectics were determined. The eutectic concentration and temperature of fusion of the eutectics increased with the melting temperature of the respective excipient. The eutectics with the self-dispersing excipients disintegrated faster than more conventional eutectics containing polyethylene glycols that were prepared for comparison. The drug particle sizes were smaller for mixtures with higher recrystallization tendency and with drug concentrations close to the eutectic concentration.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"211 ","pages":"Article 114701"},"PeriodicalIF":4.4,"publicationDate":"2025-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143709276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Starch-Based scaffold produced by FDM 3D printing technique as Innovative and biosustainable wound dressing","authors":"Franco Dominici ,&nbsp;Anna Imbriano ,&nbsp;Debora Puglia ,&nbsp;Cinzia Pagano ,&nbsp;Francesca Luzi ,&nbsp;Aurora Rafanelli ,&nbsp;Alessandro Di Michele ,&nbsp;Francesco Bonacci ,&nbsp;Maria Rachele Ceccarini ,&nbsp;Sara Primavilla ,&nbsp;Andrea Valiani ,&nbsp;Leonardo Tensi ,&nbsp;Carmen Laura Pérez Gutierrez ,&nbsp;Raquel De Melo Barbosa ,&nbsp;César Viseras ,&nbsp;Maurizio Ricci ,&nbsp;Luana Perioli","doi":"10.1016/j.ejpb.2025.114698","DOIUrl":"10.1016/j.ejpb.2025.114698","url":null,"abstract":"<div><div>Starch is a safe biopolymer, whose use for the production of scaffolds intended for deep wounds treatment is limited, due to its low mechanical and thermal properties. For this reason, until now, it has been used in low amounts and/or in combination with other biopolymers. The aim of the study was to produce thermoplastic filaments (TPS) with high starch content, useful for scaffolds production by Fusion Deposition Modelling 3D printing technique. TPS was obtained by hot melt extrusion from a mixture of starch (70 % w/w) and glycerol (30 % w/w) combined to cationic clay montmorillonite, citric acid and magnesium stearate to improve strength and processability. The prepared scaffold was characterized and compared to other two scaffolds, where the effect of the addition of polycaprolactone (PCL) or methylsulphonylmethane (MSM) (as thermostable model drug) to the blend was evaluated. The mechanical properties were investigated by Brillouin Light Scattering. In vitro studies highlighted that the scaffolds are: i) able to absorb simulated exudates (reaching a hydration of 35 % in 7 days); ii) safe on keratinocytes (viability &gt; 70 %) stimulating their growth; iii) able to inhibit <em>S. pyogenes</em> growth.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"210 ","pages":"Article 114698"},"PeriodicalIF":4.4,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143680543","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Silica-based EGFR-degrading nano-PROTACs for efficient therapy of non-small cell lung cancer","authors":"Lei Fang ,&nbsp;Ruixue Zhu ,&nbsp;Meijing Li ,&nbsp;Junhui Ma ,&nbsp;Sijun Fan ,&nbsp;Xuelian He ,&nbsp;Zhongrui Yang ,&nbsp;Yakai Yan ,&nbsp;Xiang Ma ,&nbsp;Guangya Xiang","doi":"10.1016/j.ejpb.2025.114699","DOIUrl":"10.1016/j.ejpb.2025.114699","url":null,"abstract":"<div><div>Proteolysis targeting chimeras (PROTACs) technology is a promising strategy for degrading proteins of interest. Traditional PROTACs, however, often face challenges such as poor solubility, low stability, and off-target toxicity. To address these challenges, we integrated nanotechnology to enhance the delivery of target-protein degraders to the tumor sites, thereby improving their properties. Here, we report silica-based nano-PROTACs (SiPROTACs) that feature multiple ligands on the surface to target and degrade the transmembrane protein epidermal growth factor receptor (EGFR). SiPROTACs, with a diameter of approximately 50 nm, can efficiently bind to EGFR, recruit cereblon (CRBN) to induce EGFR ubiquitination, and facilitate their degradation by proteasomes. In HCC-827 and PC-9 cell lines, SiPROTACs initiated EGFR degradation at a notably low concentration of 50 nM, demonstrating greater efficiency compared to traditional PROTACs. In HCC-827 xenograft tumor-bearing mice, SiPROTACs accumulated at tumor site for at least 48 h and exhibited significant anti-tumor effects in vivo without causing noticeable side effects. These findings suggest a novel approach for the application of PROTACs highlighting their therapeutic potential for the treatment of non-small cell lung cancer (NSCLC).</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"210 ","pages":"Article 114699"},"PeriodicalIF":4.4,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143669506","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":"Leveraging engineered yeast small extracellular vesicles serve as multifunctional platforms for effectively loading methyl salicylate through the “esterase-responsive active loading” strategy","authors":"Tianhao Li ,&nbsp;Yun Zhou ,&nbsp;Haoran Wang ,&nbsp;Junfeng Wang ,&nbsp;Rong Lu","doi":"10.1016/j.ejpb.2025.114696","DOIUrl":"10.1016/j.ejpb.2025.114696","url":null,"abstract":"<div><div>Small extracellular vesicles (sEVs) are a promising vehicle for drug delivery because of their good biocompatibility and nontoxicity. The drug loading and encapsulation efficiencies of them are not satisfactory. This is especially the case when drugs are loaded by co-incubation. In this situation, as the difference in drug concentration between the inside and outside of the membrane of ordinary sEVs decreases, the drugs cannot diffuse efficiently into the inside of the vesicles. As a result, the drug loading efficiency is low.</div><div>In this study, engineered yeast-derived small extracellular vesicles derived from Pichia pastoris X33 (XPP-sEVs) engineered with carboxylesterase 1 (CES1) were constructed using the “esterase-responsive active loading” method, which is based on the concept of prodrug design and guided by the strategy of immobilized enzymes, to improve the loading efficiency of methyl salicylate (MS) to about twice as much. This was achieved by engineering the CES1-contained small extracellular vesicles to catalyze the esterase hydrolysis reaction of MS to establish a continuous MS transmembrane concentration gradient for efficient loading of the active drugs, including methyl salicylate and its hydrolyzed active product salicylic acid.</div><div>The results showed that the enzyme activity of the CES1-sEVs group finally reached 7.88 ± 0.43 U/mL, and the drug loading efficiency was about doubled. The results of drug release from the engineered extracellular vesicles showed that the release of the drug reached equilibrium around 100 min-2 h, during which there was no sudden release of the MS, and the final amount of the drug released could be increased by 12.34 % compared with the emulsion dosage form of the MS.</div><div>Overall, the CES1-sEVs prepared in this study significantly improved the drug-loading efficiency of MS without affecting the anti-inflammatory activity of MS. The MS-CES1-sEVs prepared in this study are non-toxic and have a bright application prospect in the treatment of skin inflammation.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"210 ","pages":"Article 114696"},"PeriodicalIF":4.4,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143669505","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 “Plasma membrane depolarization reveals endosomal escape incapacity of cell-penetrating peptides” [Eur. J. Pharm. Biopharm. 184 (2023) 13949]","authors":"Marc Serulla ,&nbsp;Palapuravan Anees ,&nbsp;Ali Hallaj ,&nbsp;Evgeniya Trofimenko ,&nbsp;Tara Kalia ,&nbsp;Yamuna Krishnan ,&nbsp;Christian Widmann","doi":"10.1016/j.ejpb.2025.114694","DOIUrl":"10.1016/j.ejpb.2025.114694","url":null,"abstract":"","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"210 ","pages":"Article 114694"},"PeriodicalIF":4.4,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656471","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial to ‘Bio-material interfaces and Drug Delivery’","authors":"Eduard Preis,&nbsp;Christian Wölk,&nbsp;Claus-Michael Lehr,&nbsp;Marc Schneider,&nbsp;M.N.V. Ravi Kumar","doi":"10.1016/j.ejpb.2025.114697","DOIUrl":"10.1016/j.ejpb.2025.114697","url":null,"abstract":"","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"210 ","pages":"Article 114697"},"PeriodicalIF":4.4,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143663121","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":"Artificial gut Simulator. A scheme to predict intestinal and plasma concentration–time profiles of a weakly basic BCS-II drug, dipyridamole","authors":"Krutika Meena Harish Jain ,&nbsp;Ishaan Duggal ,&nbsp;Hao Helen Hou ,&nbsp;Ronald A. Siegel","doi":"10.1016/j.ejpb.2025.114688","DOIUrl":"10.1016/j.ejpb.2025.114688","url":null,"abstract":"<div><div>The objective of this study was to develop a scheme to predict intestinal and plasma concentration–time profiles of the weakly basic BCS-II drug, dipyridamole (DPD), using an Artificial Gut Simulator (AGS) integrated with a compartment-based disposition model. <em>In vivo</em> data for this study was obtained from previously published literature. A 3-compartment disposition model was developed using the plasma concentration–time profile of DPD following an intravenous bolus dose. The AGS, consisting of a donor cell and a hollow fiber-based absorption module, was tuned to absorb DPD saturated solution at a physiological rate constant, 0.0402 min⁻¹, based on the measured Caco-2 cell monolayer permeability coefficient. The dose dumping technique commonly used during dissolution testing can generate excessively high initial supersaturation and precipitation which is not physiologically relevant. In this study, fractions of DPD dose were added incrementally every 15 min to the AGS donor to simulate an overall first-order gastric emptying process. The concentration absorbed by the hollow fiber receiver media was input into the central compartment of the disposition model. The predicted plasma concentration–time profile matched the human <em>in vivo</em> profile of DPD obtained after oral administration of a 50 mg dose. For 30 and 90 mg oral doses, time profiles of concentration and fraction precipitated in the AGS donor agreed well with human duodenal measurements. This study demonstrates the significance of simulating physiological rate of absorption <em>in vitro</em> to accurately predict the bioavailability of a BCS-II compound.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"210 ","pages":"Article 114688"},"PeriodicalIF":4.4,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143633977","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":"Revolutionizing drug delivery strategies with probucol to combat oxidative stress in retinal degeneration: A comprehensive review","authors":"Susbin Raj Wagle ,&nbsp;Bozica Kovacevic ,&nbsp;Le Yang Sen ,&nbsp;Mengistie Diress ,&nbsp;Thomas Foster ,&nbsp;Corina Mihaela Ionescu ,&nbsp;Patrick Lim ,&nbsp;Alicia Brunet ,&nbsp;Rebekah James ,&nbsp;Livia Carvalho ,&nbsp;Armin Mooranian ,&nbsp;Hani Al-Salami","doi":"10.1016/j.ejpb.2025.114695","DOIUrl":"10.1016/j.ejpb.2025.114695","url":null,"abstract":"<div><div>Localized oxidative stress plays a key role in the development of retinal degenerative diseases, with diabetic retinopathy (DR) being one of them, contributing significantly to this vision-threatening complication of diabetes. Increased oxidative burden leads to dysfunction across various retinal cell types, including vascular endothelial cells, neurons, glial cells and pericytes. Importantly, even after achieving normalized glycemia, the detrimental effects of oxidative stress persist. Nonetheless, growing data highlights the therapeutic potential of antioxidants in safeguarding vision. However, extensive clinical trials using traditional antioxidants have produced mixed results. Therefore, probucol, known for its ability to limit vascular oxidative stress, decrease superoxide generation, and improve endogenous antioxidant activity, is a promising candidate explored in this review. In addition to describing probucol, this review will explore novel therapeutic formulation strategies by incorporating bile acid into probucol-loaded nanoparticles to enhance drug delivery to the posterior segment of the eye for more effective management of DR. The integration of bio-nanotechnology with probucol and bile acids represents a promising avenue for developing effective therapies for DR, addressing the limitations of traditional antioxidant treatments.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"210 ","pages":"Article 114695"},"PeriodicalIF":4.4,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143633978","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}