European Journal of Pharmaceutical Sciences最新文献

{"title":"The influence of protein corona on liposomal delivery systems: A comprehensive review","authors":"Solmaz Mojarad-Jabali ,&nbsp;Yousef Fatahi ,&nbsp;Rassoul Dinarvand","doi":"10.1016/j.ejps.2025.107166","DOIUrl":"10.1016/j.ejps.2025.107166","url":null,"abstract":"<div><div>Liposomes continue to play a key role in drug delivery and diagnostics, with applications in cancer therapy and vaccine formulations. Their unique characteristics enable the development of more effective delivery systems. However, the behavior of liposomes <em>in vivo</em> differs significantly from their <em>in vitro</em> performance, which can impact their clinical application. Upon systemic administration, liposomes must circulate in the body for extended periods to reach target tissues. A challenge arises when liposomes encounter biological fluids <em>in vivo</em>, where proteins and other biomolecules form a \"protein corona\" around the liposomes, which can alter their function. Despite the development of stealth liposomes, completely preventing protein corona formation remains a challenge. The presence of the protein corona can interfere with interactions between targeting ligands and tissues, potentially reducing the efficacy of targeted delivery systems. Recent studies, however, suggest that the protein corona may also be utilized to enhance liposome functionality and targeting. This review explores the formation of the protein corona on liposomes, the factors influencing the structure and composition of liposome-protein corona complexes, and strategies to control this process. It also examines <em>in vivo</em> studies on protein corona formation and its impact on liposome behavior, targeting capacity, and drug release profiles. Finally, we discuss the concept of personalized liposome-protein corona complexes for the detection of disease biomarkers <em>in vivo</em>.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"212 ","pages":"Article 107166"},"PeriodicalIF":4.3,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144293580","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":"Advancing Direct Tablet Compression with AI: A multi-task framework for quality control, batch acceptance, and causal analysis","authors":"Yazid Bounab,&nbsp;Osmo Antikainen,&nbsp;Mia Sivén,&nbsp;Anne Juppo","doi":"10.1016/j.ejps.2025.107142","DOIUrl":"10.1016/j.ejps.2025.107142","url":null,"abstract":"<div><div>Pharmaceutical manufacturing has surged in drug development with the rise of Pharma 4.0, leveraging artificial intelligence (AI) to improve efficiency, optimize resource use, and reduce production times. Direct Tablet Compression (DTC), a key manufacturing technique, depends on the physicochemical properties of active pharmaceutical ingredients (API), excipients, and process parameters. This paper presents a novel multi-task framework combining regression, classification, and text generation to predict tablet properties (friability, hardness, disintegration time, and water absorption ratio), determine batch acceptance, and provide insights for optimizing interactions to improve tablet quality. The framework not only enables real-time monitoring, quality control and regulatory compliance, but also helps to understand the reasons why tablets in the manufacturing batch do not meet quality requirements. Using statistical methods, Neural Networks (NN), Natural Language Processing (NLP), and generative AI (GenAI), it outperforms state-of-the-art methods, achieving 91.8% <span><math><msup><mrow><mi>R</mi></mrow><mrow><mn>2</mn></mrow></msup></math></span> and 95.5% accuracy for regression and classification, respectively, as demonstrated using the Harvard Dataverse V1 dataset of Fast Disintegrating Tablets (FDTs) non placebo.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"212 ","pages":"Article 107142"},"PeriodicalIF":4.3,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144293578","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":"Duloxetine's potential dual antitumor and immunomodulatory role in apoptosis and autophagy signaling pathways in cancer: In Vitro and In Vivo evidence","authors":"Ivana Nikolic ,&nbsp;Aleksandar Lazovic ,&nbsp;Isidora Stanisavljevic ,&nbsp;Marija Andjelkovic ,&nbsp;Suzana Popovic ,&nbsp;Sladjana Pavlovic ,&nbsp;Milena Jurisevic ,&nbsp;Marina Mitrovic","doi":"10.1016/j.ejps.2025.107165","DOIUrl":"10.1016/j.ejps.2025.107165","url":null,"abstract":"<div><h3>Background</h3><div>Cancer remains the second leading cause of mortality worldwide, underscoring the urgent need for novel therapeutic strategies. Drug repurposing is an effective strategy to address current cancer challenges, such as the resistance and toxicity associated with traditional chemotherapy. Among the various psychotropic drugs, antidepressants are emerging as promising candidates due to their demonstrated anticancer activity.</div></div><div><h3>Methods</h3><div>We evaluated duloxetine (DUL), a serotonin-norepinephrine reuptake inhibitor, for anticancer and immunomodulatory activity by performing comprehensive <em>in vitro</em> and <em>in vivo</em> experiments. In HCT116 (colon), HeLa (cervical), and MDA-MB-231 (triple-negative breast cancer) human cancer cells, and 4T1 mouse breast cancer cells, we investigated DUL’s cytotoxicity, apoptosis, autophagy, cell cycle arrest, and migration inhibition through MTT assay, flow cytometry, and immunofluorescence methods. An orthotopic mouse model of breast cancer was utilized to investigate the <em>in vivo</em> tumor inhibitory effects of DUL, along with its systemic toxicity and immunomodulatory properties. Gene expression (p53, Beclin-1), cytokine profile, and CD3⁺ <em>T</em> cell activation were examined by mRNA sequencing and ELISA kits to explore underlying mechanisms.</div></div><div><h3>Results</h3><div>For the first time, our <em>in vitro</em> results indicated that DUL caused dose-dependent cytotoxicity, apoptosis, autophagy, and cell cycle arrest in all cancer lines tested, which was more selective than 5-fluorouracil (5-FU). Mechanistically, DUL modulated apoptotic (Bcl-2, Bax, caspase-3), autophagic (p62), and survival (pAkt) signaling, disrupted mitochondrial membrane potential, and inhibited cell migration. <em>In vivo</em>, DUL inhibited tumor growth without inducing hepatic or renal toxicity. Notably, DUL stimulated the production of pro-inflammatory cytokines (IFN-γ, IL-1β, TNF-α), enhanced the immunity of CD3⁺ <em>T</em> cells, and increased the expression of pro-apoptotic p53 and autophagic Beclin-1 genes, reflecting its dual antitumor and immunomodulatory actions.</div></div><div><h3>Conclusion</h3><div>Our findings revealed for the first time that DUL is a promising repurposed drug for cancer treatment, as it has demonstrated proven antitumor efficacy and immune-stimulating properties. This novel dual role of DUL warrants further investigation in clinical oncology.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"212 ","pages":"Article 107165"},"PeriodicalIF":4.3,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144283116","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":"Tiny-TIM intestinal fluids versus human intestinal fluids: A comparison of their composition and solubilizing capacity for poorly soluble drugs","authors":"Brecht Goovaerts ,&nbsp;Álvaro López Mármol ,&nbsp;Joachim Brouwers ,&nbsp;Zahari Vinarov ,&nbsp;Anura S. Indulkar ,&nbsp;Thomas B. Borchardt ,&nbsp;Patrick Augustijns ,&nbsp;Mirko Koziolek","doi":"10.1016/j.ejps.2025.107150","DOIUrl":"10.1016/j.ejps.2025.107150","url":null,"abstract":"<div><div>The tiny-TIM system offers an <em>in vitro</em> platform for the simulation of physiological processes occurring in human stomach and small intestine aiding in drug product development by predicting the bioperformance of oral formulations under fasted and fed state intake conditions. To assess this <em>in vitro</em> system in terms of its physiological relevance, we performed a detailed analysis of the composition as well as the solubilizing capacity of tiny-TIM intestinal fluids (TIF), and compared this to previously collected and analysed human intestinal fluids (HIF). Moreover, the impact of meal type on TIF composition and solubilising capacity was investigated by using either a liquid meal or a solid meal. In the fasted state, TIF exhibited lower lipid concentrations with a TIF/HIF ratio of 0.27, and elevated bile salt levels (TIF/HIF ratio of 1.8). Fasted state TIF generally overpredicted the solubilizing capacity of HIF, likely due to its higher bile salt concentrations. In the fed state, TIF contained biorelevant lipid concentrations but remained monophasic without phase separation, unlike HIF. This was likely due to higher bile salt levels (5.3 times that of HIF), which solubilized all lipids into the micellar phase. This resulted on average in a 3.3-fold increase in solubility of the poorly water-soluble model compounds in the micellar fraction of TIF as compared to HIF. Shifting from a liquid to a solid meal had minimal impact on TIF composition and solubilizing capacity.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"211 ","pages":"Article 107150"},"PeriodicalIF":4.3,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144254575","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 novel physiologically based biopharmaceutics modeling (PBBM) framework using the open systems pharmacology suite, part 1: in vitro modeling of vericiguat","authors":"Paul Vrenken ,&nbsp;Maria Vertzoni ,&nbsp;Sebastian Frechen ,&nbsp;Juri Solodenko ,&nbsp;Michaela Meyer ,&nbsp;Uwe Muenster ,&nbsp;André Dallmann","doi":"10.1016/j.ejps.2025.107164","DOIUrl":"10.1016/j.ejps.2025.107164","url":null,"abstract":"<div><div>Physiologically Based Biopharmaceutics Modeling (PBBM) links <em>in vitro</em> solubility and dissolution kinetics of oral drugs to Physiologically Based Pharmacokinetic (PBPK) models, enabling the prediction of drug bioavailability. This approach reduces reliance on animal experimentation during drug development. Part 1 of this series introduces a novel, open-source PBBM workflow using the Open Systems Pharmacology (OSP) Software Suite. It combines the newly developed OSP solubility toolbox to estimate drug aqueous solubility and bile salt micelle partitioning from <em>in vitro</em> data, with an updated MoBi® dissolution model that accounts for factors such as hydrodynamic diffusion layer thickness changes and micelle partitioning.</div><div>This approach was applied to poorly soluble, highly permeable vericiguat, a first-in-class soluble guanylate cyclase (sGC) stimulator for the treatment of chronic heart failure. The solubility models effectively described the aqueous solubility-pH profile and bile salt partitioning, while the dissolution model captured the <em>in vitro</em> dissolution kinetics of various tablet formulations. Part 2 focuses on integrating developed PBBM sub-models into PBPK models using PK-Sim® to predict vericiguat’s clinical pharmacokinetics after oral administration. This PBBM workflow demonstrates potential for diverse applications, including predictive bioavailability and bioequivalence assessments, <em>in silico</em> formulation optimization, formulation bridging, dose selection, and setting dissolution specifications.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"212 ","pages":"Article 107164"},"PeriodicalIF":4.3,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144283115","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":"Towards implementing optimized methodologies and in-depth molecular profiling to assess the pharmacological potential of human lung fibroblast exosomes as bio-shuttles for cancer therapeutics","authors":"Alexandros Giannopoulos-Dimitriou ,&nbsp;Aikaterini Saiti ,&nbsp;Emmanuel Panteris ,&nbsp;Andigoni Malousi ,&nbsp;Fani Chatzopoulou ,&nbsp;Eleni Stamoula ,&nbsp;Athanasios K. Anagnostopoulos ,&nbsp;Giannis Vatsellas ,&nbsp;Passant M. Al-Maghrabi ,&nbsp;Anette Müllertz ,&nbsp;Ioulia Tseti ,&nbsp;Dimitrios G. Fatouros ,&nbsp;Ioannis S. Vizirianakis","doi":"10.1016/j.ejps.2025.107155","DOIUrl":"10.1016/j.ejps.2025.107155","url":null,"abstract":"<div><div>Despite their favorable biopharmaceutical properties, exosomes face standardization challenges in isolation and characterization, hindering the development of EV products suitable for clinical applications. The MRC-5 cell line poses a cellular model approved by regulatory affairs for drug development, facilitating the clinical translation of MRC-5 cell-derived nanotherapeutics. This study aims to: (a) identify the optimal methodology for isolating intact MRC-5 cell-derived exosomes with high purity and integrity suitable for drug delivery applications, (b) elucidate the global miRNA and proteomic profile of the isolated exosomes using high-throughput methodologies and bioinformatics, (c) investigate the exosome uptake capacity towards the “autologous” normal MRC-5, and “heterologous” malignant human lung adenocarcinoma A549 and tongue squamous HSC-3 cells, (d) evaluate the pharmacological profile of doxorubicin (DOX)- and curcumin (CUR)- loaded exosomes towards the normal and tumorigenic cells in vitro. The proposed isolation protocol combining ultrafiltration with membrane-based affinity binding, yielded non-aggregated exosomes with superior physicochemical properties. The miRNA profiling data revealed the enrichment of several tumor-suppressive miRNAs mainly involved in gene regulation pathways, whilst the proteomic profiling highlighted the role of exosomal protein in extracellular matrix remodeling. The drug delivery profiling indicated an “intrinsic” tropism of the exosomes towards the malignant A549 and HSC-3 cells. Exosomal CUR and exosomal DOX inhibited tumor cell proliferation more efficiently than free drugs, with synergistic effects upon co-administration. This study provides a comprehensive morphological, physicochemical and molecular characterization of MRC-5 cell-derived exosomes and validates the “intrinsic” tropism of CUR- and DOX- loaded exosomes towards tumorigenic cells, paving the way towards their further exploitation as drug delivery nanocarriers.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"212 ","pages":"Article 107155"},"PeriodicalIF":4.3,"publicationDate":"2025-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144265701","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":"Transplacental transfer of metformin and interaction of metformin with the uptake transporters of placental trophoblast cells","authors":"Xiaoting Gu ,&nbsp;Yutian Cai ,&nbsp;Chaoyue Zheng ,&nbsp;Keran Li ,&nbsp;Shuwen Zhu ,&nbsp;Shaohan Zhang ,&nbsp;Ziqi Wang ,&nbsp;Jianxiong Xiang ,&nbsp;Zhipeng Cheng ,&nbsp;Xiaoyu Ai ,&nbsp;Cheng Yang","doi":"10.1016/j.ejps.2025.107161","DOIUrl":"10.1016/j.ejps.2025.107161","url":null,"abstract":"<div><div>Metformin is among the most widely prescribed antidiabetic agents, with increasingly accepted by women with gestational diabetes mellitus due to its more convenient administration. Knowledge of the interaction of metformin with the uptake transporters of placental trophoblast cells is important for robust evaluation of the safety usage in pregnancy. Herein, the pregnancy pharmacokinetic study and distribution in placenta and fetus study were employed and showed that metformin could distribute quickly into the placenta and fetus, and the content of MET in the placenta was obvious higher than that in fetus. We further explored the effect of the uptake transporters on the transmembrane movement of metformin in placental trophoblast cells, and found that OCT1, OCT2, OCT3, THTR1 and THTR2 may be involved in the transplacental transfer of metformin in BeWo cells and pregnant rats. Ulteriorly, the effect of metformin on the expression of nutrient uptake transporters was evaluated on BeWo cells, which indicated that metformin may affect the fetal uptake of related nutrients from maternal blood by affecting the expression of glucose transporters, amino acid transporters, fatty acids transporters and especially vitamin transporters on placental trophoblast cells. These findings could serve as a valuable reference for the clinical utilization of metformin in pregnant individuals.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"212 ","pages":"Article 107161"},"PeriodicalIF":4.3,"publicationDate":"2025-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144265702","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":"Population pharmacokinetic and exposure-response study of a novel anti-tuberculosis drug to inform its dosage design in phase III clinical trial","authors":"Weijie Kong ,&nbsp;Hao Liang ,&nbsp;Yi Zhang ,&nbsp;Lei Li ,&nbsp;Yongguo Li ,&nbsp;Xiaoyu Yan ,&nbsp;Dongyang Liu","doi":"10.1016/j.ejps.2025.107160","DOIUrl":"10.1016/j.ejps.2025.107160","url":null,"abstract":"<div><div>Although bedaquiline (BDQ) received conditional approval for multi-drug resistance tuberculosis (MDR-TB), a black box warning was added due to QT prolongation risk. WX-081, a promising second-in-class drug that finished phase II clinical trial, exhibited comparable anti-TB activity and better cardiac safety. The accumulation of its active metabolite WX-081-M3 leads to QT prolongation, whereas the relationships between dosage, exposure and response have not been established. Accordingly, the dosage design for phase III study is challenging. Here, the first population pharmacokinetic (PPK) and exposure-response (E-R) analysis were conducted for WX-081. 1610 WX-081 and 1580 WX-081-M3 concentrations were collected from 24 healthy volunteers and 48 tuberculosis patients for PPK study. The pharmacokinetic parameters and sputum culture conversions of 20 MDR-TB patients receiving BDQ and WX-081 were used for E-R analysis. The absorption of WX-081 was well described by a three-compartments transit model, while the distribution and elimination profiles of WX-081 and WX-081-M3 were captured by three- and two-compartments models, respectively. E-R analysis demonstrated that the clinical efficacy of WX-081 is comparable with BDQ and can be evaluated by average concentration at steady state (C_avg,ss) of WX-081. According to the simulation results of different regimens, the dosage of 450 mg once daily (QD) for 1 week and subsequent 300 mg QD for 1 week followed by 150 mg QD for 22 weeks was recommended considering both efficacy and safety. Our study revealed the PK and efficacy profiles of WX-081 for the first time and proposed a dose optimization strategy to facilitate its clinical development.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"212 ","pages":"Article 107160"},"PeriodicalIF":4.3,"publicationDate":"2025-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144265700","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":"Population pharmacokinetics of isavuconazole in hematologic patients: implications for model-informed precision dosing","authors":"Diego Peña-Lorenzo ,&nbsp;José Germán Sánchez-Hernández ,&nbsp;Irene Conde-González ,&nbsp;Aránzazu Zarzuelo-Castañeda ,&nbsp;Noemí Rebollo ,&nbsp;Lourdes Vázquez-López ,&nbsp;María José Otero","doi":"10.1016/j.ejps.2025.107157","DOIUrl":"10.1016/j.ejps.2025.107157","url":null,"abstract":"<div><h3>Background</h3><div>Isavuconazole is a broad-spectrum antifungal agent used for treating invasive fungal infections (IFIs). Its pharmacokinetics may be impacted in hematologic patients due to concomitant clinical and therapeutic factors potentially affecting drug exposure. The aim of this study was to develop a population pharmacokinetic (popPK) model of isavuconazole in adult hematologic patients to support model-informed precision dosing.</div></div><div><h3>Materials and method</h3><div>Prospective, non-controlled study performed in adult hematologic patients receiving isavuconazole for IFIs and followed up by a therapeutic drug monitoring (TDM) program. Isavuconazole plasma concentrations were quantified using an ultra-high-performance liquid chromatography (UPLC) with UV detector. A popPK model was developed using NONMEM v.7.5.0. Simulations were based on the final model to evaluate the differences across physiological variables with impact on drug exposure.</div></div><div><h3>Results</h3><div>A one-compartment model with first-order absorption and elimination described adequately 121 isavuconazole concentrations from 52 patients. Body surface area (BSA) and serum albumin (ALB) significantly influenced drug clearance. The final popPK model showed good precision, robustness, and predictive performance, supporting its use for individualized isavuconazole dosing in this population.</div></div><div><h3>Conclusions</h3><div>BSA and serum ALB were identified as covariates influencing isavuconazole clearance in adult hematologic patients. Further studies are needed to better characterize the absorption of isavuconazole and implications on dosage recommendations, especially for higher proposed doses.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"212 ","pages":"Article 107157"},"PeriodicalIF":4.3,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144257709","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":"Archaeosomal nanocarriers improve pharmacokinetics and bioavailability of vancomycin after oral administration","authors":"Viktor Sedlmayr ,&nbsp;Julian Quehenberger ,&nbsp;David Wurm ,&nbsp;Mikko Gynther ,&nbsp;Rebecca Vieth ,&nbsp;Valerie Dürr ,&nbsp;Pascal Gesse ,&nbsp;Oliver Spadiut ,&nbsp;Gert Fricker ,&nbsp;Philipp Uhl","doi":"10.1016/j.ejps.2025.107159","DOIUrl":"10.1016/j.ejps.2025.107159","url":null,"abstract":"<div><div>Vancomycin, a glycopeptide antibiotic, is typically administered intravenously (IV) for severe Gram-positive bacterial infections. While the oral route offers higher patient adherence, it is limited by poor mucosal transport, restricting its use to intestinal infections. To address these challenges, this study explores the encapsulation of vancomycin into archaeosomes -phospholipid-based nanocarriers incorporating archaeal lipids, which exhibit exceptional stability in the gastrointestinal environment and interact specifically with enterocytes. Previous work demonstrated that lipid nanocarrier formulations benefit from the incorporation of the archaeal lipid calditolglycerocaldarchaeol (GCTE), facilitating mucosal barrier penetration and increasing bioavailability <em>in vivo</em>. In this study, we investigated the effects of archaeal lipid extract (ALE) and purified caldarchaeol (GDGT) on the pharmacokinetics and oral bioavailability of vancomycin in male Wistar rats. Our findings reveal that archaeosomal formulations significantly increase systemic exposure by prolonging circulation time and enhancing plasma drug concentrations, combined with high biocompatibility. Notably, the oral bioavailability (as measured by the area under the curve, AUC) increased 9-fold with GDGT liposomes and 4-fold with ALE liposomes compared to free vancomycin. These results highlight the potential of archaeal lipid-based drug delivery systems to enable oral administration of therapeutics that are traditionally injection-only.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"212 ","pages":"Article 107159"},"PeriodicalIF":4.3,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144257706","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}