European Journal of Pharmaceutics and Biopharmaceutics最新文献_第3页

Cationic liposome-mediated intra-articular delivery of lorecivivint for osteoarthritis treatment 阳离子脂质体介导的关节内给药治疗骨关节炎。

IF 4.3 2区医学 Q1 PHARMACOLOGY & PHARMACY

European Journal of Pharmaceutics and Biopharmaceutics

Pub Date : 2026-01-08 DOI: 10.1016/j.ejpb.2026.114980

Paula Gonzalez-Fernandez , Luca Morici , Luca Simula , Rajhi Takwa , Aya Benabdellah , Eric Allémann , Olivier Jordan

Osteoarthritis (OA) is the most common joint disease worldwide causing cartilage loss, inflammation and pain. Lorecivivint (LOR) is a new disease-modifying osteoarthritis drug (DMOAD) that targets the Wnt pathway to improve cartilage regeneration and reduce the pro-inflammatory cytokines production. However, its advancement in the clinical evaluation is facing certain challenges due to poor solubility and fast clearance from the joint. Our study is the first to improve LOR delivery using cationic liposomes for intra-articular injection.

DSPC-Chol-DOTAP-based liposomes were formulated using microfluidics with an encapsulation efficiency (EE) of 36 % of LOR and increasing the drug solubility over 120-fold in PBS and 100-fold in simulated synovial fluid. In a physiological environment, a prolonged release of 17 % of the LOR over 14 days was achieved, while faster release of 65 to 86 %, respectively, was observed in simulated synovial fluid. The surface charge of + 35 mV and the size of 145 nm were influential in increasing cartilage uptake in bovine explant of 1.4-fold and 3.6-fold compared to free LOR solution and suspension, respectively.

In vitro study by flow cytometry revealed there was no cytotoxicity at 10 nM in human chondrocytes (hCHs) and in human mesenchymal stem cells (MSCs). Nevertheless, some toxicity-related morphological changes in hCHs spheroids were observed at 300 nM, which corresponds to the IC80 of LOR. The safer liposomal concentration of 10 nM maintained the drug bioactivity and reduced by half TGF-β and IL-6 levels in two-dimensional hCHs and MSCs cell culture, which confirmed the anti-fibrotic and anti-inflammatory effects. An in vivo pilot study was conducted using a severe ACLT-hMnX rat model showing preliminary evidence of an alleviated osteophyte formation and reduced cartilage matrix loss in the medial tibial plateau. Overall, Lipo-LOR improved drug solubility, release and cartilage retention, which are critical requirements for implementing a localized intra-articular OA therapy.

骨关节炎（OA）是世界上最常见的关节疾病，引起软骨损失，炎症和疼痛。lorecvivint （LOR）是一种新的疾病改善性骨关节炎药物（DMOAD），其靶向Wnt通路，促进软骨再生，减少促炎细胞因子的产生。然而，由于其溶解性差，从关节中清除快，其在临床评价中的进展面临一定的挑战。我们的研究首次改善了关节内注射用阳离子脂质体给药的效果。采用微流体制备了dspc - cholo - dotapl脂质体，其包封效率（EE）为36 %，药物在PBS中的溶解度提高了120倍，在模拟滑液中的溶解度提高了100倍。在生理环境中，在14 天内实现了17 %的LOR延长释放，而在模拟滑液中分别观察到65至86 %的更快释放。表面电荷 + 35 mV和尺寸145 nm对牛外植体软骨摄取的影响分别是游离LOR溶液和悬浮液的1.4倍和3.6倍。体外流式细胞术研究显示，10 nM对人软骨细胞（hCHs）和人间充质干细胞（MSCs）无细胞毒性。然而，在300 nM时，hCHs球体出现了一些与毒性相关的形态学变化，对应于LOR的IC80。较安全的脂质体浓度为10 nM维持了药物生物活性，并使二维hCHs和MSCs细胞培养中TGF-β和IL-6水平降低一半，证实了其抗纤维化和抗炎作用。使用严重ACLT-hMnX大鼠模型进行的体内初步研究显示，初步证据表明减轻了胫骨平台内侧骨赘形成和减少了软骨基质损失。总的来说，lipoo - lor改善了药物的溶解度、释放和软骨保留，这是实施局部关节内OA治疗的关键要求。

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引用次数: 0

Injectable poloxamer-based thermogel as a delivery platform for agmatine and hyaluronic acid in muscle tissue engineering 可注射波洛莫热凝胶作为肌肉组织工程中酰胺和透明质酸的递送平台。

IF 4.3 2区医学 Q1 PHARMACOLOGY & PHARMACY

European Journal of Pharmaceutics and Biopharmaceutics

Pub Date : 2026-01-08 DOI: 10.1016/j.ejpb.2026.114983

Mohammad Qutub , Amol Tatode , Tanvi Premchandani , Jayshree Taksande , Milind Umekar

Volumetric muscle loss (VML) results in permanent functional deficits for which current therapeutic strategies are insufficient. We hypothesized that an injectable, thermoresponsive hydrogel enabling localized delivery of agmatine sulfate (AgS) and hyaluronic acid (HA) could synergistically promote robust neuromuscular regeneration. A poloxamer-based thermogel was systematically optimized using a 3² full factorial design. The lead formulation exhibited a physiologically advantageous gelation temperature (27 ± 1.03°C) and time (42 ± 1.4 s), with rapid bioactive release (85–90% within 18–24 h) matched to the critical satellite cell activation window. In vitro degradation studies confirmed complete gel erosion, providing burst delivery during the acute injury phase. In a rat tibialis anterior VML model, the AgS-HA combination therapy demonstrated profound synergistic effects, restoring grip strength and normalizing complex gait parameters to near-control levels. This functional recovery was corroborated by significantly reduced serum creatine kinase, indicating reduced muscle damage. Histopathological analysis revealed near-complete restitution of mature, organized myofiber architecture with minimal fibrosis, contrasting with extensive scar tissue in control groups. Notably, functional recovery occurred without significant modulation of systemic inflammatory markers (IL-6, IL-10, TNF-α), suggesting regeneration proceeds through direct pro-myogenic, anti-fibrotic, and neurovascular mechanisms rather than systemic anti-inflammatory effects. These findings demonstrate that a thermoresponsive hydrogel platform for rapid AgS and HA delivery effectively promotes comprehensive structural and functional recovery, representing a potent and clinically translatable strategy for VML.

体积性肌肉损失（VML）导致永久性的功能缺陷，目前的治疗策略是不够的。我们假设一种可注射的热反应性水凝胶能够局部递送硫酸agmatine （AgS）和透明质酸（HA），可以协同促进强健的神经肌肉再生。采用32全因子设计系统地优化了基于poloxmer的热凝胶。铅制剂具有生理优势的凝胶温度（27 ± 1.03°C）和时间（42 ± 1.4 s），其生物活性快速释放（18-24 h内85-90%）与关键的卫星细胞激活窗口相匹配。体外降解研究证实了完全的凝胶侵蚀，在急性损伤阶段提供爆裂递送。在大鼠胫骨前肌VML模型中，AgS-HA联合治疗显示出深刻的协同效应，恢复握力并使复杂的步态参数正常化至接近控制水平。血清肌酸激酶显著降低证实了这种功能恢复，表明肌肉损伤减少。组织病理学分析显示，与对照组广泛的瘢痕组织相比，成熟、有组织的肌纤维结构几乎完全恢复，纤维化最小。值得注意的是，在系统炎症标志物（IL-6、IL-10、TNF-α）没有明显调节的情况下，功能恢复发生了，这表明再生是通过直接的促肌、抗纤维化和神经血管机制进行的，而不是通过系统的抗炎作用。这些研究结果表明，用于快速递送AgS和HA的热响应性水凝胶平台有效地促进了全面的结构和功能恢复，代表了一种有效的临床可翻译的VML策略。

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引用次数: 0

Novel drug-drug cocrystal form of Luteolin with Metformin: Improved solubility, bioavailability, and in vitro anticancer activity 木犀草素与二甲双胍的新型药物-药物共晶形式：提高溶解度、生物利用度和体外抗癌活性。

IF 4.3 2区医学 Q1 PHARMACOLOGY & PHARMACY

European Journal of Pharmaceutics and Biopharmaceutics

Pub Date : 2026-01-07 DOI: 10.1016/j.ejpb.2026.114985

Ningrong Wang , Jianing Zhao , Yiwu Wang , Xuanheng Chen , Yuejia Wu , Anqiang Wang , Yanyan Chen , Dan He , Yi Hou , Yongjun Gan

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 < 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.

由于木犀草素（Luteolin, Lut）水溶性极低，口服生物利用度差，单药疗效有限，严重限制了其临床应用。为了克服这些局限性，本研究采用乙醇慢冷却重结晶的方法，成功地合成了木犀草素与二甲双胍（Met）以1:1 M的比例合成的药用共晶（Lut-Met）。单晶x射线衍射证实共晶Lut-Met属于单斜晶系（空间群P21/n），其中Lut和Met通过分子内氢键、分子间氢键（如Met- n4 - h4b…O2-Lut）和π-π堆叠相互作用保持稳定。物理化学表征表明，与纯Lut相比，Lut- met的熔点降低，吸湿性增加。在0.2% SDS和3%乙醇溶液中的溶出性能分别提高了7.6倍和4.8倍。小鼠药代动力学评价显示，与单个药物及其物理混合物相比，Lut的相对口服生物利用度（基于AUC0-24h， p 50）提高了3.13倍。此外，体内分布研究显示，在共晶治疗后，Lut在肿瘤相关器官（包括心脏、肝脏、脾脏和肾脏）的积累增强。本研究证实了与Met共结晶可以同时提高Lut的溶解度、生物利用度和抗癌功效，为Lut的药物开发提供了一个有前景的策略。

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引用次数: 0

Enhancing bioavailability of a weakly basic drug through cocrystallization: PBPK modeling of ketoconazole–succinic acid 通过共结晶提高弱碱性药物的生物利用度：酮康唑-琥珀酸的PBPK模型

IF 4.3 2区医学 Q1 PHARMACOLOGY & PHARMACY

European Journal of Pharmaceutics and Biopharmaceutics

Pub Date : 2026-01-07 DOI: 10.1016/j.ejpb.2026.114986

Ana Karolina Santos Goes , Amira Soliman , Venkata Krishna Kowthavarapu , Paulo Renato Oliveira , Natalia Valadares de Moraes

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.

药物共晶是通过将活性药物成分（API）与合适的共晶结合而形成的，它提供了一种很有前途的策略，可以增强药物的溶解度、稳定性和溶解性，从而在不改变药理学性质的情况下改善吸收和生物利用度。这种方法对难溶性药物尤其有利，如酮康唑（KTZ），这是一种BCS II类化合物，其特点是溶出性有限吸收和可变的口服生物利用度。KTZ是一种弱双碱性药物，具有ph依赖性，有利于酸性胃条件下的溶解。为了克服ph依赖性溶解，开发了KTZ与琥珀酸（SA）共晶，并采用基于生理的药代动力学（PBPK）方法，通过体外溶解度和溶出度数据来预测KTZ或KTZ-SA共晶给药后的KTZ血浆浓度谱。对开发的PBPK模型进行了验证，KTZ的预测/观测AUC比在2倍范围内。该模型成功地捕获了奥美拉唑对KTZ的减少暴露。PBPK模拟显示，与健康受试者（AUC: 12.2µg·h·mL-1）相比，在氯水条件下（AUC: 1.1µg·h·mL-1）或奥美拉唑（AUC: 3.1µg·h·mL-1）给药200 mg后，KTZ暴露减少。相比之下，KTZ-SA共晶在健康受试者（AUC: 17.2µg·h·mL-1）、氯水合人群（AUC: 18.6µg·h·mL-1）或与奥美拉唑共给药（AUC: 16.9µg·h·mL-1）中的暴露量一致相似。这种基于模型的方法已经证明了KTZ-SA共晶在与胃酸相关的差异人群中提高生物利用度的潜力，有效地解决了胃酸变化带来的挑战。这些发现支持了药物共晶的发展，以优化药物传递和最大化治疗效果。

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引用次数: 0

Factors affecting flash nanoprecipitation of Pharmaceuticals: Principles and applications 影响药物闪蒸纳米沉淀的因素：原理和应用。

IF 4.3 2区医学 Q1 PHARMACOLOGY & PHARMACY

European Journal of Pharmaceutics and Biopharmaceutics

Pub Date : 2026-01-07 DOI: 10.1016/j.ejpb.2026.114984

Wisdom Awuku, Bi-Botti Celestin Youan

Flash nanoprecipitation (FNP) has emerged as a transformative technique in the preparation of nanoparticles for targeted drug delivery. Traditional drug delivery systems often struggle with challenges such as poor solubility, limited bioavailability, and suboptimal targeting. FNP addresses these limitations through a one-step, scalable process that produces nanoparticles with tunable size, composition, morphology, and surface characteristics. This review explores the principles of FNP, focusing on its application in encapsulating bioactive agents, achieving controlled release, and enhancing bioavailability. Unlike conventional emulsification or antisolvent precipitation methods, FNP utilizes rapid mixing under kinetically controlled conditions to achieve high reproducibility and uniform particle distribution. The technique has been successfully employed for various pharmaceutical applications, including the delivery of small molecules, biologics, and nucleic acids. Beyond laboratory research, FNP has been adopted in industrial and clinical settings—for instance, in the scalable production of lipid nanoparticles (LNPs) for mRNA-based vaccines and other nucleic acid therapeutics—demonstrating its translational potential. Furthermore, its adaptability extends to theranostic and imaging applications. The review highlights critical formulation variables and process parameters, such as polymer type and its glass transition temperature, solvent selection, and Reynolds number, which influence key characteristics such as nanoparticle stability and performance. By synthesizing recent advances, this paper provides a comprehensive overview of how FNP is already transforming drug delivery, highlighting its current impact, and future research directions.

闪速纳米沉淀法（FNP）已成为一种变革性的技术，用于制备靶向药物递送的纳米颗粒。传统的给药系统经常面临溶解度差、生物利用度有限和靶向性不佳等挑战。FNP通过一步、可扩展的工艺解决了这些限制，生产出具有可调尺寸、组成、形态和表面特征的纳米颗粒。本文综述了FNP的原理，重点介绍了FNP在生物活性药物包封、控释和提高生物利用度等方面的应用。与传统的乳化或抗溶剂沉淀方法不同，FNP在动力学控制条件下快速混合，以实现高重现性和均匀的颗粒分布。该技术已成功应用于各种制药应用，包括小分子、生物制剂和核酸的输送。除实验室研究外，FNP已被应用于工业和临床环境中，例如用于mrna疫苗和其他核酸疗法的脂质纳米颗粒（LNPs）的规模化生产，证明了其转化潜力。此外，它的适应性扩展到治疗和成像应用。本文重点介绍了影响纳米颗粒稳定性和性能等关键特性的关键配方变量和工艺参数，如聚合物类型及其玻璃化转变温度、溶剂选择和雷诺数。通过综合近年来的研究进展，本文全面概述了FNP如何改变药物传递，突出了其目前的影响和未来的研究方向。

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引用次数: 0

Tuning the in vivo transfection efficiency of mRNA-Loaded lipoplexes by PEG-Lipid structure and ratio 通过peg -脂质结构和比例调节mrna负载脂质体的体内转染效率。

IF 4.3 2区医学 Q1 PHARMACOLOGY & PHARMACY

European Journal of Pharmaceutics and Biopharmaceutics

Pub Date : 2026-01-03 DOI: 10.1016/j.ejpb.2026.114981

O.V. Markov , D.N. Antropov , E.V. Shmendel , P.A. Puchkov , O.A. Yakovlev , M.D. Kerbitskaya , E.S. Zhuravlev , A.S. Dome , E.P. Goncharova , D.N. Shcherbakov , M.A. Zenkova , M.A. Maslov , G.A. Stepanov

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 in vivo 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 in vivo 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.

基于mrna的抗病毒和抗肿瘤治疗正在迅速发展，并显示出相当大的前景。优化脂质体递送载体的组成对提高mRNA疫苗的效力至关重要。在其成分中，peg -脂质需要精心优化，以提高mRNA-脂质体复合物的胶体稳定性，延长其体内循环时间，提高mRNA的传递效率，从而引发强大的免疫反应。在这里，我们报告了基于阳离子脂质2X3和辅助脂质DOPE的阳离子脂质体中peg -脂质的结构-功能分析。PEG-脂类的以下参数是不同的：PEG链长（800-2000 Da）、PEG-脂类结构（经典的头尾结构与双分子结构）、疏水锚链长度（C14十八烷基和C18十四烷基残基）和配方中PEG-脂类的摩尔量（0.5-4 摩尔%）。我们证明，优化的脂质体含有4 摩尔%的peg -脂质，由线性PEG2000通过氨基甲酸酯连接剂偶联到c14 -二烷基甘油锚定物。该制剂能够在体内高效表达荧光素酶编码mRNA，并在递送甲型流感/California//07/09 （H1N1pdm09）血凝素编码mRNA后，诱导强大的抗原特异性体液和细胞免疫。我们的研究结果强调了peg -脂质优化对于推进抗病毒和抗肿瘤疫苗的有效mRNA递送平台的重要性。

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引用次数: 0

Humectant-plasticized poly(vinyl alcohol)-sericin hydrogels with improved dimensional stability and moisture retention for wound dressing applications 湿润增塑型聚乙烯醇-丝胶水凝胶，具有更好的尺寸稳定性和保湿性，用于伤口敷料应用。

IF 4.3 2区医学 Q1 PHARMACOLOGY & PHARMACY

European Journal of Pharmaceutics and Biopharmaceutics

Pub Date : 2026-01-03 DOI: 10.1016/j.ejpb.2026.114982

Thunyaluk Meetam , Rungnapha Yamdech , Pithi Chanvorachote , Pornanong Aramwit

This study investigated the development of poly(vinyl alcohol) (PVA)/sericin hydrogels incorporating humectant-plasticizers glycerin, propylene glycol, and mannitol for wound dressing applications. Although PVA/sericin hydrogels exhibit excellent cytocompatibility and promote fibroblast proliferation and collagen production, making them promising candidates for wound care, they suffer from rapid moisture loss and dimensional instability. To address these limitations, glycerin, propylene glycol, and/or mannitol were incorporated to enhance the properties of the hydrogels. The physicochemical and mechanical properties, together with the in vitro cytocompatibility of L929 fibroblasts, were evaluated. The results demonstrated that incorporating propylene glycol and/or mannitol improved dimensional stability, skin adhesion, moisture retention, exudate absorption, flexibility, and softness. Among all the formulations, the hydrogel containing 1 % v/v propylene glycol and 1 % w/v mannitol exhibited the most balanced performance, combining superior physicochemical and mechanical properties (time to initial upward bending: 2.83 h; time for complete upward bending of all four edges: 10.50 h; gel fraction: 60 %, highest absorption at 3 h: 34.41 %; tensile strength: 46.93 kPa, elastic modulus: 33.53 kPa, compressive strength: 19.94 kPa; compressive modulus: 15.58 kPa) with enhanced fibroblast viability (102 % cell viability) and sustained sericin release (∼90 % cumulative release at 168 h). In vitro assays confirmed the cytocompatibility of the optimized hydrogel. Taken together, these findings indicate its potential for effective management of moderately exudating wounds. This study introduces a simple and practical plasticization approach for PVA/sericin hydrogels, offering a promising candidate for wound dressing applications. Further clinical studies are warranted to evaluate its therapeutic efficacy and safety.

本研究探讨了含有湿润增塑剂甘油、丙二醇和甘露醇的聚乙烯醇/丝胶凝胶在伤口敷料中的应用。尽管PVA/丝胶水凝胶具有良好的细胞相容性，促进成纤维细胞增殖和胶原蛋白的产生，使其成为伤口护理的有希望的候选者，但它们具有快速的水分流失和尺寸不稳定性。为了解决这些限制，加入了甘油、丙二醇和/或甘露醇来增强水凝胶的性能。对L929成纤维细胞的理化、力学性能及体外细胞相容性进行了评价。结果表明，加入丙二醇和/或甘露醇可以改善尺寸稳定性、皮肤粘附性、保湿性、渗出物吸收性、柔韧性和柔软性。在所有的配方中,水凝胶含有1 % v / v丙二醇,1 % w /甘露醇展出最均衡的性能,结合优越的物理化学和力学性能(初始向上弯曲时间:2.83 h;时间完成向上弯曲的四个边:10.50 h;凝胶分数:60 %,最高吸收3 h: 34.41 %;抗拉强度:46.93 kPa,弹性模量:33.53 kPa,抗压强度:19.94 kPa;压缩模量：15.58 kPa)，增强成纤维细胞活力（102 %细胞活力）和持续的丝胶蛋白释放（在168 h累积释放约90 %）。体外实验证实了优化后的水凝胶的细胞相容性。综上所述，这些发现表明其在中度渗出性伤口的有效管理潜力。本研究介绍了一种简单实用的PVA/丝胶水凝胶的塑化方法，为伤口敷料的应用提供了一个有前途的候选材料。需要进一步的临床研究来评价其治疗效果和安全性。

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引用次数: 0

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] “纳米凝胶治疗慢性和术后伤口：生物工程乳铁蛋白-金银花-海藻酸盐系统增强组织再生和炎症消退”的更正[欧洲]。j .制药。生物医学工程学报，2009(5):349 - 349。

IF 4.3 2区医学 Q1 PHARMACOLOGY & PHARMACY

European Journal of Pharmaceutics and Biopharmaceutics

Pub Date : 2025-12-27 DOI: 10.1016/j.ejpb.2025.114969

Samaa Abdullah , Samar Thiab , Abeer A. Altamimi , Alaa A. Al-Masud , Meshal Marzoog Al-Sharafa , Hatim S. AlKhatib , Imad Hamadneh

引用次数: 0

Co-administering clofazimine with infant formula enhances its oral bioavailability in rats and pigs 氯法齐明与婴儿配方奶粉联合使用可提高其在大鼠和猪体内的口服生物利用度。

IF 4.3 2区医学 Q1 PHARMACOLOGY & PHARMACY

European Journal of Pharmaceutics and Biopharmaceutics

Pub Date : 2025-12-23 DOI: 10.1016/j.ejpb.2025.114979

Thomas Eason , Ellie Ponsonby-Thomas , Anna C. Pham , Shouyuan Huang , Simone Margaard Offersen , Thomas Thymann , Vanessa Zann , Malinda Salim , Ben J. Boyd

Milk-based formulations have been proposed as enabling formulations for the delivery of poorly water-soluble drugs to children due to their safety, dose versatility and ability to improve drug solubilisation through the digestion process. In this study the feasibility of using commercially available infant formula as an enabling formulation to enhance the solubilisation and oral bioavailability of clofazimine, a poorly soluble lipophilic drug, following oral administration was investigated. The solubilisation of crystalline clofazimine in digesting infant formula was assessed in vitro using synchrotron small-angle X-ray scattering. An in vivo pharmacokinetic study was then conducted to determine the oral bioavailability of a suspension of clofazimine in infant formula compared to a lipid-free aqueous suspension in both a rat and piglet animal model. Clofazimine administered in infant formula produced significantly higher plasma concentrations than the aqueous vehicle and resulted in comparable enhancements in relative oral bioavailability in both the piglet (235%) and rat animal models (256%). Results from this study demonstrated that infant formula was an effective enabling formulation, with a positive correlation between improved drug solubilisation during in vitro digestion of infant formula and enhanced in vivo drug exposure following oral administration. Infant formula therefore offers an inexpensive and scalable formulation approach for improving the bioavailability of paediatric drugs, like clofazimine, and enabling the treatment of infections in children.

由于其安全性、剂量控制的通用性和通过消化过程改善药物溶解的能力，牛奶基配方已被提议作为给儿童提供水溶性差药物的可行配方。在这项研究中，研究了在口服给药后，使用市售婴儿配方奶粉作为增强氯法齐明（一种难溶性亲脂药物）的增溶性和口服生物利用度的可行性。采用同步加速器小角x射线散射法研究了氯法齐明晶体在婴儿配方奶粉消化中的增溶作用。然后，在大鼠和仔猪动物模型中进行了体内药代动力学研究，以确定婴儿配方奶粉中氯法齐明悬浮液与无脂水悬浮液的口服生物利用度。氯法齐明在婴儿配方奶粉中的血浆浓度明显高于水溶液，在仔猪（235%）和大鼠动物模型（256%）中，氯法齐明的相对口服生物利用度都有相当的提高。本研究的结果表明，婴儿配方奶粉是一种有效的促进配方，在婴儿配方奶粉体外消化过程中改善药物增溶性与口服给药后增加体内药物暴露之间存在正相关关系。因此，婴儿配方奶粉为提高氯法齐明等儿科药物的生物利用度和治疗儿童感染提供了一种廉价和可扩展的配方方法。

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引用次数: 0

Sulfasalazine–quercetin co-amorphous systems: Sustained release behaviors and enhanced pharmacokinetics 柳氮磺胺吡啶-槲皮素共无定形体系：缓释行为和增强的药代动力学。

IF 4.3 2区医学 Q1 PHARMACOLOGY & PHARMACY

European Journal of Pharmaceutics and Biopharmaceutics

Pub Date : 2025-12-22 DOI: 10.1016/j.ejpb.2025.114972

Jia Deng , Jiangying Li , Yangwen Peng , Qian Dai , Ningbo Pang , Zhe Wang , Hailu Zhang , Xin Chen

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 T_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.

柳氮磺胺吡啶（SULF）是一种公认的治疗类风湿性关节炎（RA）和炎症性肠病（IBD）的药物，但其口服吸收受到外排转运蛋白，特别是MRP2和BCRP的限制。因此，需要每日高剂量（1-3 g）和频繁给药（每日三至四次），这增加了长期治疗期间不良反应的风险。为了克服这些限制，本研究开发了SULF与槲皮素（QUE）的共无定形体系（CASs）。采用粉末x射线衍射（PXRD）、偏振光显微镜（PLM）、扫描电镜（SEM）和温度调制差示扫描量热法（mDSC）对CASs进行了系统表征。通过傅里叶变换红外光谱（FTIR）和分子动力学（MD）模拟进一步阐明了分子水平的形成机理。所有的SULF- que CASs都表现出113 °C左右的玻璃化转变温度，并表现出缓释行为，在6 h后，SULF的溶解（24.5-42.9 %）明显低于结晶形式（89.8 %）。这种减少归因于原位形成致密的“贝壳状”再结晶QUE表面结构，这是由于其不均匀溶解造成的。重要的是，与结晶型磺胺砜相比，共无定形形式表现出更高的口服生物利用度（1.52-2.80倍）和延长的Tmax（1.84-5.52倍），实现了其开发的最初目标。此外，随着时间的推移，这些系统表现出令人满意的物理稳定性。总体而言，SULF- que CASs为优化SULF的临床剂量、减少副作用以及为RA和IBD提供协同治疗方法提供了一种有希望的策略。

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