European Journal of Pharmaceutics and Biopharmaceutics最新文献

{"title":"Trp2 cationic liposomes doped with manganese adjuvant potently activate dendritic cells to enhance antitumor activity against melanoma in mice","authors":"Chengke Ding,&nbsp;Huiting Li,&nbsp;Pengbo Han,&nbsp;Yan Zhao","doi":"10.1016/j.ejpb.2026.114991","DOIUrl":"10.1016/j.ejpb.2026.114991","url":null,"abstract":"<div><div>Tyrosinase-related protein 2 (Trp2) peptide-based vaccines hold great promise for melanoma immunotherapy, however, their application is often limited by inefficient antigen delivery, inadequate dendritic cell (DC)-mediated immune activation, and an immunosuppressive tumor microenvironment. To address these challenges, we developed an engineered cationic liposome vaccine platform for co-delivering Trp2 and a manganese-based adjuvant (MnJ). The Trp2-DOTAP-Lipo/MnJ system facilitates efficient antigen delivery to antigen-presenting cells via electrostatic interactions between the cationic lipid bilayer and negatively charged cell membranes, significantly enhancing antigen uptake, promoting DC maturation, stimulating the secretion of pro-inflammatory cytokines such as tumor necrosis factor alpha (TNF-α) and levels of interleukin-6 (IL-6), and increasing cytotoxic T lymphocyte infiltration. Acting as a key amplifier of antigen-specific immunity, MnJ enhances antigen presentation and effector functions, which together with its role in localizing cytokine production, potently enhances anti-tumor immunity while minimizing systemic toxicity. In a murine melanoma model, Trp2-DOTAP-Lipo/MnJ exhibited significantly improved tumor suppression and extended survival. By combining nanocarrier engineering with innate immune activation, this strategy offers a robust combinatory therapeutic approach for melanoma, leveraging efficient antigen delivery and localized immunomodulation to overcome key obstacles in cancer immunotherapy.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"221 ","pages":"Article 114991"},"PeriodicalIF":4.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145976675","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":"Sulfasalazine–quercetin co-amorphous systems: Sustained release behaviors and enhanced pharmacokinetics","authors":"Jia Deng ,&nbsp;Jiangying Li ,&nbsp;Yangwen Peng ,&nbsp;Qian Dai ,&nbsp;Ningbo Pang ,&nbsp;Zhe Wang ,&nbsp;Hailu Zhang ,&nbsp;Xin Chen","doi":"10.1016/j.ejpb.2025.114972","DOIUrl":"10.1016/j.ejpb.2025.114972","url":null,"abstract":"<div><div>Sulfasalazine (SULF) is a well-established therapeutic agent for rheumatoid arthritis (RA) and inflammatory bowel disease (IBD), but its oral absorption is limited by efflux transporters, particularly MRP2 and BCRP. Consequently, high daily doses (1–3 g) and frequent administration (three to four times daily) are required, increasing the risk of adverse effects during long-term therapy. To overcome these limitations, co-amorphous systems (CASs) of SULF with quercetin (QUE) were developed in this study. The CASs were systematically characterized using powder X-ray diffraction (PXRD), polarized light microscopy (PLM), scanning electron microscopy (SEM), and temperature-modulated differential scanning calorimetry (mDSC). The molecular-level formation mechanism was further elucidated via Fourier-transform infrared spectroscopy (FTIR) and molecular dynamics (MD) simulations. All SULF–QUE CASs exhibited glass transition temperatures around 113 °C and demonstrated sustained-release behavior, with markedly lower SULF dissolution (24.5–42.9 %) compared to the crystalline form (89.8 %) after 6 h. This reduction was attributed to the in situ formation of a dense “shell-like” recrystallized QUE surface structure resulting from its incongruent dissolution. Importantly, co-amorphous forms demonstrated enhanced oral bioavailability (1.52–2.80-fold) and prolonged <em>T</em>_max (1.84–5.52-fold) compared to crystalline SULF, fulfilling the original goal of their development. Moreover, these systems exhibited satisfactory physical stability over time. Overall, the SULF–QUE CASs present a promising strategy to optimize the clinical dosage of SULF, reduce side effects, and offer a synergistic therapeutic approach for RA and IBD.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"220 ","pages":"Article 114972"},"PeriodicalIF":4.3,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145827148","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":"Novel drug-drug cocrystal form of Luteolin with Metformin: Improved solubility, bioavailability, and in vitro anticancer activity","authors":"Ningrong Wang ,&nbsp;Jianing Zhao ,&nbsp;Yiwu Wang ,&nbsp;Xuanheng Chen ,&nbsp;Yuejia Wu ,&nbsp;Anqiang Wang ,&nbsp;Yanyan Chen ,&nbsp;Dan He ,&nbsp;Yi Hou ,&nbsp;Yongjun Gan","doi":"10.1016/j.ejpb.2026.114985","DOIUrl":"10.1016/j.ejpb.2026.114985","url":null,"abstract":"<div><div>Due to the extremely low water solubility, poor oral bioavailability, and limited monotherapeutic efficacy of Luteolin (Lut), its clinical application is severely restricted. To overcome these limitations, this study successfully synthesized and characterized the pharmaceutical cocrystal (Lut-Met) with a 1:1 M ratio of Luteolin and Metformin (Met) using the ethanol slow cooling recrystallization method. Single-crystal X-ray diffraction confirmed that cocrystal Lut-Met belongs to the monoclinic crystal system (space group P2_1/n), in which Lut and Met are stable through intramolecular hydrogen bonds, intermolecular hydrogen bonds (e.g., Met-N4-H4B…O2-Lut), and π-π stacking interactions. Physicochemical characterization demonstrated a reduced melting point and increased hygroscopicity for the Lut-Met compared to pure Lut. Its dissolution performance in 0.2% SDS and 3% ethanol solution increased by 7.6 times and 4.8 times, respectively. The pharmacokinetic evaluation in mice revealed a 3.13-fold improvement in the relative oral bioavailability of Lut (based on AUC_0-24h, p &lt; 0.0001) after administration of the cocrystal. In vitro CCK-8 assays demonstrated that the Lut-Met cocrystal exhibits enhanced anti-tumor activity against HeLa, A549, and HepG2 cancer cell lines, as evidenced by its significantly lower IC₅₀ values compared to both individual drugs and their physical mixture. Furthermore, in vivo distribution studies showed enhanced accumulation of Lut in tumor-related organs, including the heart, liver, spleen, and kidney, following cocrystal treatment. This study confirms that cocrystallization with Met can simultaneously enhance the solubility, bioavailability, and anticancer efficacy of Lut, offering a promising strategy for its pharmaceutical development.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"220 ","pages":"Article 114985"},"PeriodicalIF":4.3,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145943009","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":"Enhancing bioavailability of a weakly basic drug through cocrystallization: PBPK modeling of ketoconazole–succinic acid","authors":"Ana Karolina Santos Goes ,&nbsp;Amira Soliman ,&nbsp;Venkata Krishna Kowthavarapu ,&nbsp;Paulo Renato Oliveira ,&nbsp;Natalia Valadares de Moraes","doi":"10.1016/j.ejpb.2026.114986","DOIUrl":"10.1016/j.ejpb.2026.114986","url":null,"abstract":"<div><div>Pharmaceutical cocrystals, formed by combining an active pharmaceutical ingredient (API) with a suitable coformer, offer a promising strategy to enhance drug solubility, stability, and dissolution, thereby improving absorption and bioavailability without altering pharmacological properties. This approach is particularly advantageous for poorly soluble drugs such as ketoconazole (KTZ), a BCS Class II compound characterized by dissolution-limited absorption and variable oral bioavailability. As a weak dibasic drug, KTZ exhibits pH-dependent dissolution, which was favored under acidic gastric conditions. To overcome the pH-dependent dissolution, a cocrystal of KTZ with succinic acid (SA) was developed and a physiologically based pharmacokinetic (PBPK) approach informed by in vitro solubility and dissolution data was used to predict KTZ plasma concentration profiles, following administration of KTZ or KTZ-SA cocrystal. The developed PBPK model was verified, with a predicted/observed AUC ratio within a 2-fold range for KTZ. The model successfully captured the reduced exposure to KTZ when administered with omeprazole. PBPK simulations demonstrated a reduced KTZ exposure following a 200 mg dose under achlorhydric conditions (AUC: 1.1 µg·h·mL-1) or with omeprazole administration (AUC: 3.1 µg·h·mL-1), compared to healthy subjects (AUC: 12.2 µg·h·mL-1). In contrast, KTZ-SA cocrystal achieved consistently similar exposure in healthy subjects (AUC: 17.2 µg·h·mL-1), achlorhydric populations (AUC: 18.6 µg·h·mL-1), or when coadministered with omeprazole (AUC: 16.9 µg·h·mL-1). This model-based approach has demonstrated the potential of KTZ-SA cocrystal to enhance bioavailability in populations with achlorhydria-related disparities, effectively addressing the challenges posed by variable gastric acidity. The findings support the development of pharmaceutical cocrystals to optimize drug delivery and maximize therapeutic outcomes.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"220 ","pages":"Article 114986"},"PeriodicalIF":4.3,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145939736","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":"Reflection paper on the APV workshop on in vitro performance testing of topically applied and topically acting substances","authors":"Dominique Lunter ,&nbsp;Sascha Gorissen ,&nbsp;Michael Herbig ,&nbsp;Martin Hukauf ,&nbsp;Adina Eichner","doi":"10.1016/j.ejpb.2025.114971","DOIUrl":"10.1016/j.ejpb.2025.114971","url":null,"abstract":"<div><div>With great anticipation, the European Medicines Agency (EMA) guideline titled <em>“Quality and Equivalence of Locally Applied, Locally Acting Cutaneous Products”</em> officially came into effect on April 2, 2025. This regulatory document establishes the legal and scientific framework for the evaluation of generic topical medicinal products, particularly those for which systemic bioavailability is not a relevant endpoint. The guideline is designed to replace conventional clinical trials with scientifically justified alternative methodologies for demonstrating therapeutic equivalence to reference products in the context of generic marketing authorization. These methodologies include, most notably, <em>in vitro</em> release testing (IVRT), <em>in vitro</em> permeation testing (IVPT), stratum corneum sampling via tape stripping (TS), and the vasoconstriction assay for corticosteroids. Based on the draft guideline version released in 2018, preliminary experience has been gathered in recent years regarding the implementation and practical applicability of some testing parameters proposed. However, this early engagement also exposed several ambiguities and limitations in the draft guidance, prompting expectations that the finalized version would address these deficiencies and offer more comprehensive direction on the use of these methods. The present paper is intended to summarize these known limitations and critically examine selected aspects of the guideline. Thereby, it seeks to provide an informed perspective on the scope, robustness, and regulatory utility of the final guideline, and to facilitate a dialogue on its practical implementation in regulatory and industrial settings.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"220 ","pages":"Article 114971"},"PeriodicalIF":4.3,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145818632","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":"Does slowly reversible binding to keratin contribute to stratum corneum reservoir function?","authors":"Abigail M. Poehls ,&nbsp;Johannes M. Nitsche ,&nbsp;Gerald B. Kasting","doi":"10.1016/j.ejpb.2025.114936","DOIUrl":"10.1016/j.ejpb.2025.114936","url":null,"abstract":"<div><div>The existence of a storage capacity or reservoir function within human stratum corneum (HSC) for topically applied chemicals is well documented. However, the source of this reservoir remains ambiguous and may well depend on the chemical and the exposure conditions. We have investigated the role of reversible binding to keratin in contributing to this phenomenon by measuring the kinetics of uptake and desorption of solutes from isolated HSC, delipidized HSC, and silicone membrane from buffered aqueous solutions (pH 5.5) in vitro. A lipophilic permeant, geraniol, was studied for periods ranging from 24 to 168 h. Additional desorption data for testosterone and 1-propanol from isolated HSC were drawn from the literature. Results were compared with theoretical predictions for a homogeneous membrane with either no binding, equilibrium binding or slowly reversible binding. The theory includes a hitherto unpublished analysis of the short-time and long-time behavior of such systems. Calculations were also conducted for selected corticosteroids, the original stimuli for the HSC reservoir function concept. The HSC and delipidized HSC data for geraniol were most consistent with slowly reversible binding in the protein phase of the tissue. Almost complete desorption was achieved within 2–3 h of exposure to permeant-free buffer. Testosterone and 1-propanol data were consistent with this picture. Model-based calculations for corticosteroids, however, predict much longer retention times in the stratum corneum – up to two weeks – when extrapolated to the case of partially hydrated skin. We conclude that, while slowly reversible binding of many lipophilic permeants in the protein phase of the tissue is supported, the combination of very low diffusion rates in the lipid phase with strong equilibrium binding in the protein phase is a major contributor to HSC reservoir function for corticosteroids.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"220 ","pages":"Article 114936"},"PeriodicalIF":4.3,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145556495","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":"Exploration of a dual-mimetic mucus inert nanocomplex for enhanced oral insulin delivery","authors":"Qiyao Zhai ,&nbsp;Shuang Guo ,&nbsp;Zhixiang Cui ,&nbsp;Lu Qin ,&nbsp;Jian Guan ,&nbsp;Xin Zhang ,&nbsp;Shirui Mao","doi":"10.1016/j.ejpb.2025.114970","DOIUrl":"10.1016/j.ejpb.2025.114970","url":null,"abstract":"<div><div>The development of oral insulin delivery systems has advanced significantly, with polyelectrolyte nanocomplexes (PEC) showing promise due to their solvent-free synthesis. However, their efficacy is limited by poor mucus penetration and intestinal absorption. Inspired by the nature of mucin, chitosan (CS) modified with proline, threonine and serine to mimic the mucin’s PTS sequence were synthesized to enhance mucus permeability of the PEC. To further improve the mucus permeability and the <em>trans</em>-epithelial transport of the PEC, muco-penetrating nanocomplexes were fabricated by utilizing hyaluronic acid (HA), thus forming a surface with high-density positive and negative charges to mimic the surface charge properties of viruses. The nanocomplexes were self-assembled using modified CS and insulin, followed by HA coating. It was demonstrated that the nanocomplexes exhibited good physical stability, enhanced protection against enzymatic degradation, and increased penetration efficiency across the mucus layer and small intestine compared to unmodified counterparts. Furthermore, the <em>in vivo</em> hypoglycemic study further revealed a 2.16-fold increase in relative pharmacological availability for the nanocomplexes over the CS/Ins PEC Collectively, these findings reveal the potential of (PTS-CS/Ins)/HA, a dual-mimicking muco-penetrating nanocomplex based on the nature of mucin and virus, as a promising platform for oral insulin delivery.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"220 ","pages":"Article 114970"},"PeriodicalIF":4.3,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145801954","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 “Nanogel therapy for chronic and post-surgical wounds: a bioengineered Lactoferrin–Acacia–Alginate system enhancing tissue regeneration and inflammatory resolution” [Eur. J. Pharm. Biopharm. 219 (2026) 114952]","authors":"Samaa Abdullah ,&nbsp;Samar Thiab ,&nbsp;Abeer A. Altamimi ,&nbsp;Alaa A. Al-Masud ,&nbsp;Meshal Marzoog Al-Sharafa ,&nbsp;Hatim S. AlKhatib ,&nbsp;Imad Hamadneh","doi":"10.1016/j.ejpb.2025.114969","DOIUrl":"10.1016/j.ejpb.2025.114969","url":null,"abstract":"","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"220 ","pages":"Article 114969"},"PeriodicalIF":4.3,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145849568","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":"Novel PLA-based shape-memory formulation: Design, preparation, and evaluation for gastro-retentive delivery of 5-fluorouracil to enhance oral bioavailability","authors":"Fengxue Liu ,&nbsp;Xuefei Yu ,&nbsp;Yanmei Wu ,&nbsp;Ting Zhu ,&nbsp;Ning Chen ,&nbsp;Hao Chen ,&nbsp;Wei Shen ,&nbsp;Wei Zheng","doi":"10.1016/j.ejpb.2025.114968","DOIUrl":"10.1016/j.ejpb.2025.114968","url":null,"abstract":"<div><div>5-fluorouracil (5-FU) is one of the most effective chemotherapeutic drugs for various solid tumors. However, its low water solubility and limited absorption rates in the stomach are crucial limitations that prevent it from being effectively applied in clinical practice. To address these issues, we first encapsulated 5-FU in β-cyclodextrin (5-FU–β-CD) to enhance its solubility, and the resulting 5-FU–β-CD was then loaded into a PLA film to prepare a novel gastro-retentive drug delivery system (GRDDS) based on shape-memory properties. The excipients, such as tributyl citrate (TBC), hydroxyethyl cellulose (HEC), citric acid (CA), and sodium bicarbonate (NaHCO₃), were incorporated into the PLA matrix at an optimized ratio. This was done to enhance the performance of PLA as an ideal matrix material in GRDDS, including improvements in drug release, floating behavior, shape recovery, gastric retention, and in vivo anti-tumor activity. The results suggested that the solubility of the 5-FU–β-CD inclusion complex was significantly enhanced, which was 1.88-fold higher than that of pure 5-FU. The optimal shape-memory drug delivery formulation, 5-FU–β-CD–PLA/TBC (86/14), prepared in this study consists of PLA/TBC (86/14) incorporating 3 % HEC, 3 % NaHCO₃, 1 % CA, and 3 % 5-FU. Its gastric retention time was notably prolonged to approximately 8 h following oral administration in mice, whereas the residual amount of 5-FU–β-CD at this time point was much lower than the initial loading. The oral bioavailability of the 5-FU–β-CD–PLA/TBC (86/14) was 269 % higher than that of pure 5-FU. Additionally, the mean tumor size and weight in the mouse model of gastric carcinoma administered with 5-FU–β-CD–PLA/TBC (86/14) were 215.3 mm³ and 241.4 mg respectively, significantly smaller than those in the 5-FU group. This indicates that the novel PLA-based drug delivery system has significantly enhanced anti-tumor effects. Its excellent therapeutic effects were further confirmed through HE, Ki67, and TUNEL staining. Taken together, 5-FU–β-CD–PLA/TBC (86/14) can be retained in the stomach to improve relative bioavailability. This system represents a promising carrier not only for 5-FU but also for other poorly soluble drugs that require prolonged retention in the stomach.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"220 ","pages":"Article 114968"},"PeriodicalIF":4.3,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145803457","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":"Tuning the in vivo transfection efficiency of mRNA-Loaded lipoplexes by PEG-Lipid structure and ratio","authors":"O.V. Markov ,&nbsp;D.N. Antropov ,&nbsp;E.V. Shmendel ,&nbsp;P.A. Puchkov ,&nbsp;O.A. Yakovlev ,&nbsp;M.D. Kerbitskaya ,&nbsp;E.S. Zhuravlev ,&nbsp;A.S. Dome ,&nbsp;E.P. Goncharova ,&nbsp;D.N. Shcherbakov ,&nbsp;M.A. Zenkova ,&nbsp;M.A. Maslov ,&nbsp;G.A. Stepanov","doi":"10.1016/j.ejpb.2026.114981","DOIUrl":"10.1016/j.ejpb.2026.114981","url":null,"abstract":"<div><div>The development of mRNA-based antiviral and antitumor therapeutics is progressing rapidly and shows considerable promise. Optimizing the composition of liposomal delivery vehicles is critical for enhancing mRNA vaccine efficacy. Among their components, PEG-lipids require careful optimization to improve the colloidal stability of mRNA-liposome complexes, prolong their <em>in vivo</em> circulation time, and enhance mRNA delivery efficiency, thereby eliciting a robust immune response. Here, we report a structure-functional analysis of PEG-lipids incorporated into cationic liposomes based on the cationic lipid 2X3 and the helper lipid DOPE. The following parameters of PEG-lipids were varied: PEG chain length (800–2000 Da), PEG-lipid architecture (classical head-to-tail vs. gemini-like structures), hydrophobic anchor chain length (C14 octadecyl and C18 tetradecyl residues) and molar amount of PEG-lipid in formulations (0.5–4 mol%). We demonstrated that optimized liposomes contained 4 mol% of a PEG-lipid composed of linear PEG2000 conjugated to a C14-dialkylglycerol anchor via a carbamate linker. This formulation enabled efficient <em>in vivo</em> expression of luciferase-encoding mRNA and, upon delivery of influenza A/California//07/09 (H1N1pdm09) hemagglutinin-encoding mRNA, induced robust antigen-specific humoral and cellular immunity. Our findings underscore the critical importance of PEG-lipid optimization for advancing potent mRNA delivery platforms for antiviral and antitumor vaccines.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"220 ","pages":"Article 114981"},"PeriodicalIF":4.3,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145905642","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}