European Journal of Pharmaceutical Sciences最新文献_第3页

Scoping review to identify data needs and environmental hotspots for future LCA Studies: Insights into pharmaceutical excipients and processes 确定未来LCA研究的数据需求和环境热点的范围审查：对药物赋形剂和工艺的见解。

IF 4.7 3区医学 Q1 PHARMACOLOGY & PHARMACY

European Journal of Pharmaceutical Sciences

Pub Date : 2026-01-27 DOI: 10.1016/j.ejps.2026.107453

Anja Autzen Virtanen , Satu Lakio , Atif Madi , Mia Sivén

In recent years, the environmental assessment and optimization of pharmaceutical dosage forms have received increasing attention. Consequently, interest in Life Cycle Assessments (LCA) has grown, and LCA is rapidly becoming the standard method of environmental evaluations across many industries, including the pharmaceutical sector. LCA is, however, a high entry barrier method requiring expertise, software- and database access, and process specific experimentally obtained performance data (e.g. electricity consumption). In the context of pharmaceuticals, significant challenges arise due to the limited availability of input data. Because of these limitations, we wanted to investigate the feasibility of using a scoping review as an alternative to LCA for evaluating the environmental implications of pharmaceuticals. In this literature review, a total of 8788 articles were screened, of which 117 were relevant. The search was anchored in a formulation previously developed. In this formulation, 3.0 mm minitablets were manufactured by direct compression from a spray-dried amorphous solid dispersion of indomethacin in polyvinylpyrrolidone (PVP) or hydroxypropyl methylcellulose acetate succinate (HPMCAS) with the additional use of milled lactose monohydrate (LACT), microcrystalline cellulose (MCC) and magnesium stearate (MgSt) as tablet excipients. Through the systematic literature review, relevant environmental information was found for most of the processes and excipients investigated. Research currently undertaken at the intersection of environmental review and pharmaceutical manufacturing shows an upward trend. Most notably, recent research indicates that excipients generally regarded as safe (GRAS) may not necessarily be without environmental concern. Furthermore, excipients may be manufactured through multiple different routes which muddles the environmental comparison of different options. Still, this literature review identified a marked absence of sustainability-themed research specific to pharmaceutical manufacturing. With the issues uncovered, more research is sorely needed to provide guidance in formulation choices.

近年来，药物剂型的环境评价与优化越来越受到人们的关注。因此，人们对生命周期评估（LCA）的兴趣日益浓厚，LCA正迅速成为包括制药行业在内的许多行业环境评估的标准方法。然而，LCA是一种进入门槛很高的方法，需要专业知识、软件和数据库访问以及特定过程的实验获得的性能数据（例如电力消耗）。在药品方面，由于输入数据的可用性有限，出现了重大挑战。由于这些限制，我们想研究使用范围审查作为LCA的替代方法来评估药物的环境影响的可行性。本次文献综述共筛选8788篇，其中相关文献117篇。搜索是在先前开发的公式中进行的。在该配方中，用喷雾干燥的无定形固体分散体（聚乙烯吡罗烷酮（PVP）或羟丙基甲基乙酸丁二酸纤维素（HPMCAS））直接压缩制成3.0 mm的微型片剂，另外使用研磨的乳糖一水合物（LACT）、微晶纤维素（MCC）和硬脂酸镁（MgSt）作为片剂辅料。通过系统的文献回顾，发现了大多数研究的工艺和辅料的相关环境信息。目前在环境审查和制药制造交叉领域进行的研究显示出上升趋势。最值得注意的是，最近的研究表明，通常被认为是安全的辅料（GRAS）可能不一定没有环境问题。此外，辅料可以通过多种不同的途径制造，这混淆了不同选择的环境比较。尽管如此，本文献综述确定了明显缺乏可持续发展为主题的研究，具体到制药制造。随着这些问题的发现，迫切需要更多的研究来提供配方选择的指导。

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引用次数: 0

Revealing the Morphology of Small Multilamellar Lipid Nanoparticles (SMLPs) made by In-Vial Homogenization 揭示瓶内均质法制备的小多层脂质纳米颗粒（SMLPs）的形态

IF 4.7 3区医学 Q1 PHARMACOLOGY & PHARMACY

European Journal of Pharmaceutical Sciences

Pub Date : 2026-01-26 DOI: 10.1016/j.ejps.2026.107451

Sevda Akcesme , Stefanie Schmager , Yassir Al-Tikriti , Lars Gedda , Magnus Bergström , Katarina Edwards , Heiko Heerklotz , Ulrich Massing

Previous research shows that thermosensitive small multilamellar lipid nanoparticles (tSMLPs) offer promising features for temperature-triggered cytostatic drug delivery, remaining completely stable at body temperature (37°C) and releasing their payload under mild hyperthermia conditions (42°C). A distinguishing characteristic of tSMLPs is their unique particle morphology - multiple tightly packed bilayers with progressively decreasing intermembrane spacing toward the particle core. In this study, we shift the focus from their thermosensitivity to an in-depth exploration of the particle’s morphology. Using in-vial homogenization by dual centrifugation (DC) at very high lipid concentrations (60%), we prepare SMLPs composed of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and 1,2-dipalmitoyl-sn-glycero-3-phosphodiglycerol (DPPG₂). A systematic screening of DPPC/DPPG₂ 100-x/x (mol/mol) from x = 0 to 100 enabled the formation of SMLPs with sizes below 200 nm, narrow size distribution and well-distinguishable morphologies. These lipid nanoparticles also demonstrated the capacity to entrap hydrophilic compounds, despite their multilamellar structure and thus limited interlamellar aqueous space. We propose that specific headgroup interactions between DPPC and DPPG₂ underlie the observed water influx upon dilution of the initially formed vesicular phospholipid gels (VPGs) during in-vial homogenization by DC. With a combination of biophysical techniques (DLS, Time-resolved fluorescence, SAXS and WAXS) and morphological analysis (cryo-EM), we present a hypothesis to explain the evolving SMLP morphology as a function of increasing DPPG₂ content in the phospholipid blend.

先前的研究表明，热敏小多层脂质纳米颗粒（tSMLPs）为温度触发的细胞抑制药物递送提供了有希望的特性，在体温（37°C）下保持完全稳定，并在轻度高温条件下（42°C）释放其有效载荷。tsmlp的一个显著特征是其独特的颗粒形态-多层紧密排列的双层，膜间间距逐渐减小。在这项研究中，我们将焦点从它们的热敏性转移到对颗粒形态的深入探索。在非常高的脂质浓度（60%）下，使用双离心（DC）的瓶内均质，我们制备了由1,2-双棕榈酰- n-甘油-3-磷酸胆碱（DPPC）和1,2-双棕榈酰- n-甘油-3-磷酸二甘油酯（DPPG2）组成的smlp。系统筛选DPPC/DPPG2 100-x/x (mol/mol)，从x = 0到100，可以形成尺寸小于200 nm，尺寸分布窄，形态易于区分的smlp。这些脂质纳米颗粒也显示出捕获亲水化合物的能力，尽管它们是多层结构，因此限制了层间的水空间。我们提出，DPPC和DPPG2之间的特定头基相互作用是DC在瓶内均质过程中稀释初始形成的囊泡磷脂凝胶（VPGs）时观察到的水内流的基础。结合生物物理技术（DLS，时间分辨荧光，SAXS和WAXS）和形态分析（cro - em），我们提出了一个假设来解释SMLP形态的进化是磷脂混合物中DPPG2含量增加的函数。

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引用次数: 0

Construction of in situ temperature-sensitive gel of Tegafur derivative TAK5399 and its evaluation against breast cancer 替加氟衍生物TAK5399原位温敏凝胶的构建及其抗乳腺癌作用评价。

IF 4.7 3区医学 Q1 PHARMACOLOGY & PHARMACY

European Journal of Pharmaceutical Sciences

Pub Date : 2026-01-25 DOI: 10.1016/j.ejps.2026.107452

Hong Shao , Wen Li , Zhuohan Li , Peng Shi , Zheng Li , Yuxiang Wang , Chao Pi , Lingmao Zhao , Wenwu Zheng , Yumeng Wei , Ling Zhao

Tegafur (FT) is widely used in the treatment of breast cancer. However, it has poor efficacy and significant toxic side effects. In this study, we first modified FT with aspirin to obtain a new FT derivative, named TAK5399. Then, TAK5399 in situ thermosensitive gel (TAK5399-TSG) was prepared using poloxamer F68 and F127 as carriers, and evaluated in vitro and in vivo. Among the five tested tumor cell lines, TAK5399 exhibited the highest sensitivity toward human breast cancer cells (MCF-7), with an inhibition rate 8.41 times higher than that of FT. Its potential anti-breast cancer mechanism may be related to inhibiting the PI3K/AKT signaling pathway to induce apoptosis and blocking the S phase of the cell cycle. The optimal formulation process for TAK5399-TSG is F127: 24.0%, F68: 6.5%, TAK5399 content of 1.25 mg/mL, and curing time of 24 hours. The maximum drug solubility, gelation temperature, and dissolution time were 1.25 mg/mL, 31 ± 0.21°C, and 6.5 ± 0.25 h, respectively. The Cmax of TAK5399-TSG administered via in situ injection was 15.5% and 23.8% of that of oral and in situ injection of TAK5399, respectively. In tumor-bearing mice, the tumor inhibition rates of oral TAK5399 and in situ injection of TAK5399-TSG were 1.28-fold and 1.82-fold higher than those of oral FT, respectively, with good biocompatibility. In conclusion, TAK5399-TSG is an in situ gel delivery system with potential for the treatment of breast cancer.

替加富（FT）被广泛用于治疗乳腺癌。但其疗效差，毒副作用明显。在本研究中，我们首先用阿司匹林修饰FT，得到一种新的FT衍生物，命名为TAK5399。然后，以波洛沙姆F68和F127为载体制备TAK5399原位热敏凝胶（TAK5399- tsg），并进行体外和体内评价。在5个被测试的肿瘤细胞系中，TAK5399对人乳腺癌细胞（MCF-7）的敏感性最高，抑制率是FT的8.41倍。其潜在的抗乳腺癌机制可能与抑制PI3K/AKT信号通路诱导细胞凋亡，阻断细胞周期S期有关。TAK5399- tsg的最佳配方为：F127: 24.0%, F68: 6.5%， TAK5399含量为1.25 mg/mL，固化时间为24小时。最大药物溶解度为1.25 mg/mL，凝胶温度为31±0.21℃，溶解时间为6.5±0.25 h。原位注射TAK5399- tsg的Cmax分别为口服和原位注射TAK5399的15.5%和23.8%。在荷瘤小鼠中，口服TAK5399和原位注射TAK5399- tsg的抑瘤率分别比口服FT高1.28倍和1.82倍，具有良好的生物相容性。总之，TAK5399-TSG是一种具有治疗乳腺癌潜力的原位凝胶递送系统。

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引用次数: 0

Minimizing Aggregates when Nebulizing Antibody Fab Fragments: High Thermostability and High Concentration are Key. 雾化抗体Fab片段时最大限度地减少聚集：高热稳定性和高浓度是关键。

IF 4.7 3区医学 Q1 PHARMACOLOGY & PHARMACY

European Journal of Pharmaceutical Sciences

Pub Date : 2026-01-22 DOI: 10.1016/j.ejps.2026.107446

Josi Ann Steinke, Pierre-Louis Destruel, Benjamin Weiche, Stefan Dengl, Gregoire Schwach, Gerhard Pohlmann, Marlon J Hinner

The therapeutic potential of inhaled biologics is limited by protein instability during aerosolization, which can cause aggregation and increase immunogenicity risks. This study aims to identify key molecular and formulation parameters that minimize the aggregation of antibody Fab fragments during vibrating mesh nebulization. A set of 14 engineered Fabs with a broad range of melting temperatures (T_m 60-90°C) were nebulized using two different commercial vibrating mesh devices. We systematically assessed the impact of Fab thermostability, protein concentration (10-80 mg/mL), formulation excipients, and nebulizer device on the formation of high molecular weight species (HMWS) and subvisible particles (SVP). Aerosol characteristics, including fine particle fraction (FPF) and output rate, were also evaluated. High intrinsic thermostability and high protein concentration were identified as the two most critical factors for preventing aggregation. Fabs with a T_m above 80°C demonstrated exceptional stability with negligible aggregation. We attribute this effect to a correlation of high T_m with a higher resistance against unfolding and therefore a better tolerance against nebulization-induced stresses, in particular air/liquid interfacial stress. Counterintuitively, increasing the protein concentration from 10 mg/mL to 80 mg/mL suppressed aggregation for all Fabs, which had the highest benefit for Fabs with lower thermostability. This effect can at least in part be explained by a saturation of the air/liquid interface at higher Fab concentrations. While higher concentrations modestly reduced nebulizer output rates, the overall inhalable protein output (mg protein/min) was significantly enhanced. In comparison, full-length monoclonal antibodies showed poor aerosolization performance at high concentrations. Our findings provide clear guidance for developing inhaled Fab therapeutics. To ensure stability and minimize aggregation, priority should be given to selecting Fabs with high thermostability (T_m > 80°C) and formulating them at high concentrations (≥ 40 mg/mL). These strategies are expected to mitigate aggregation-induced immunogenicity and concomitant safety risks, facilitating the development of the next generation of inhaled protein drugs.

吸入生物制剂的治疗潜力受到雾化过程中蛋白质不稳定的限制，这可能导致聚集并增加免疫原性风险。本研究旨在确定振动网雾化过程中最大限度减少抗体Fab片段聚集的关键分子和配方参数。采用两种不同的商用振动网装置，对14个具有广泛熔化温度（Tm 60-90°C）的工程晶圆厂进行雾化。我们系统地评估了Fab热稳定性、蛋白质浓度（10-80 mg/mL）、配方辅料和雾化器装置对高分子量物质（HMWS）和亚可见颗粒（SVP）形成的影响。气溶胶特性，包括细颗粒分数（FPF）和输出速率也进行了评估。高固有热稳定性和高蛋白质浓度被认为是防止聚集的两个最关键因素。Tm高于80°C的晶圆片表现出优异的稳定性，聚集可以忽略不计。我们将这种效应归因于高Tm与更高的抗展开阻力的相关性，因此对雾化诱导的应力，特别是空气/液体界面应力具有更好的耐受性。与直觉相反，将蛋白浓度从10 mg/mL增加到80 mg/mL抑制了所有fab的聚集，这对热稳定性较低的fab有最大的好处。这种效应至少可以部分解释为在较高的Fab浓度下空气/液体界面的饱和。虽然较高的浓度适度降低了喷雾器的输出速率，但总体可吸入蛋白质输出（mg蛋白/分钟）显着提高。相比之下，全长单克隆抗体在高浓度下表现出较差的雾化性能。我们的发现为开发吸入式Fab疗法提供了明确的指导。为了确保稳定性和减少聚集，应优先选择具有高热稳定性（Tm > 80°C）的晶圆片，并在高浓度（≥40 mg/mL）下配制。这些策略有望减轻聚集诱导的免疫原性和伴随的安全风险，促进下一代吸入蛋白药物的开发。

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引用次数: 0

Design of co-lyophilised ternary insulin-sucrose-polymer systems with enhanced amorphous glass stability 具有增强非晶玻璃稳定性的共冻干三元胰岛素-蔗糖-聚合物体系的设计。

IF 4.7 3区医学 Q1 PHARMACOLOGY & PHARMACY

European Journal of Pharmaceutical Sciences

Pub Date : 2026-01-22 DOI: 10.1016/j.ejps.2026.107450

Claudia Giannachi , Evin Allen , Sonja Vucen , Abina Crean

The glass stability of lyophilized amorphous peptide formulations, intended for incorporation into solid oral dosage forms, require stabilisation against the challenges of manufacturing, storage and handling temperature and humidity. High glass transition temperature (Tg) polymers, polyvinylpyrrolidone (PVP) and polyvinylpyrrolidone-vinyl acetate (PVPVA), were added to insulin-sucrose formulations to enhance glass stability when exposed to temperature and humidity. Tg and onset glass transition humidity (RHg) parameters were experimentally determined as indicators of formulation glass stability with respect to temperature and humidity, respectively. A mixture design of experiment approach was employed to determine the influence of insulin, sucrose and polymer composition on formulation Tg and RHg. Statistical regression models were established to evaluate the relationship between formulation composition and the corresponding glass transition parameters, Tg and RHg. Phase separation noted for PVPVA-containing formulations, undermined regression model goodness of fit. Insulin content was shown to have a negative effect on both formulation Tg and RHg. Formulation Tg appeared to be influenced by insulin’s dynamical temperature rather than a previously reported insulin Tg value. Insulin-sucrose and insulin-polymer interactive effects resulted in increased Tg and RHg values, indicating enhanced formulation glass stability. Formulation optimization for maximized Tg and RHg identified a formulation composed of 26 % w/w insulin, 40 % w/w sucrose, and 34 % w/w PVP, with a predicted Tg of 82 °C and RHg of 60 % RH. The enhanced glass stability of the ternary insulin-sucrose-polymer formulations offers potential advantages for the manufacture, storage and handling of peptide containing oral dosage forms.

冻干无定形肽制剂的玻璃稳定性，用于合并到固体口服剂型中，需要针对制造，储存和处理温度和湿度的挑战进行稳定。在胰岛素-蔗糖配方中加入高玻璃化转变温度（Tg）聚合物，聚乙烯吡咯烷酮（PVP）和聚乙烯吡咯烷酮-醋酸乙烯酯（PVPVA），以提高暴露在温度和湿度下的玻璃稳定性。实验确定Tg和起始玻璃转变湿度（RHg）参数分别作为配方玻璃稳定性的温度和湿度指标。采用实验法的混合设计，确定胰岛素、蔗糖和聚合物组成对配方Tg和RHg的影响。建立统计回归模型，评价配方成分与相应玻璃化转变参数Tg和RHg之间的关系。相分离注意到pvpva含有配方，破坏了回归模型的拟合优度。胰岛素含量对Tg和RHg的形成均有负面影响。制剂Tg似乎受到胰岛素动态温度的影响，而不是先前报道的胰岛素Tg值。胰岛素-蔗糖和胰岛素-聚合物的相互作用导致Tg和RHg值增加，表明配方玻璃稳定性增强。为实现Tg和RHg的最优化，确定了一个由26% w/w胰岛素、40% w/w蔗糖和34% w/w PVP组成的配方，预测Tg为82°C， RHg为60% RH。三元胰岛素-蔗糖-聚合物配方的玻璃稳定性增强，为含有口服剂型的肽的制造、储存和处理提供了潜在的优势。

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引用次数: 0

Empowering the Pharmaceutical Workforce for the Digital Future. 赋能制药员工，迎接数字化未来。

IF 4.7 3区医学 Q1 PHARMACOLOGY & PHARMACY

European Journal of Pharmaceutical Sciences

Pub Date : 2026-01-21 DOI: 10.1016/j.ejps.2026.107449

Natalie Maclean, Susanna Abrahmsén-Alami, Catriona Clark, Frederik Dörr, Alastair Florence, Jarkko Ketolainen, Morten Lindow, Jérôme Mantanus, Jukka Rantanen, Gavin Reynolds, Amy Robertson, Daniel Markl

The pharmaceutical industry is undergoing a rapid digital transformation. These changes are reshaping drug substance and drug product development and manufacturing, creating both opportunities and challenges that span pharmaceutical sciences, data science, and automation engineering. However, significant skills gaps persist, limiting the sector's ability to fully leverage digital technologies and sustain innovation. This paper explores the shifting digital and data science skills needs within the pharmaceutical industry, with a focus on industrial pharmacy and pharmaceutical sciences in the UK and Europe. We examine the key technological transformations reshaping the sector, the evolution of job roles, and the attributes required of the future workforce. Building on these insights, we propose an integrated approach to skills development that spans the entire career lifecycle - from embedding digital competencies in higher education to supporting lifelong learning through flexible, industry-aligned continuing professional development. Addressing these skills gaps requires coordinated action from academia, industry, and policymakers. By fostering a collaborative, interdisciplinary, and adaptive learning ecosystem, the pharmaceutical sector can equip its workforce to thrive in a rapidly changing landscape and continue improving global health and wellbeing.

制药行业正在经历快速的数字化转型。这些变化正在重塑原料药和药品的开发和制造，为制药科学、数据科学和自动化工程创造了机遇和挑战。然而，巨大的技能差距仍然存在，限制了该行业充分利用数字技术和持续创新的能力。本文探讨了制药行业中不断变化的数字和数据科学技能需求，重点关注英国和欧洲的工业制药和制药科学。我们研究了重塑该行业的关键技术变革、工作角色的演变以及未来劳动力所需的属性。基于这些见解，我们提出了一种跨越整个职业生命周期的综合技能开发方法——从在高等教育中嵌入数字能力，到通过灵活的、与行业一致的持续专业发展支持终身学习。解决这些技能差距需要学术界、工业界和政策制定者采取协调一致的行动。通过培育协作、跨学科和适应性学习生态系统，制药行业可以使其员工在快速变化的环境中茁壮成长，并继续改善全球健康和福祉。

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引用次数: 0

From fungistatic to cytotoxic: Nano-engineered griseofulvin triggers redox-mediated apoptosis in colon cancer 从抑菌到细胞毒性：纳米工程灰黄霉素触发氧化还原介导的结肠癌细胞凋亡。

IF 4.7 3区医学 Q1 PHARMACOLOGY & PHARMACY

European Journal of Pharmaceutical Sciences

Pub Date : 2026-01-17 DOI: 10.1016/j.ejps.2026.107447

Jihad Mahmoud Alsofany , Soha Osama Hassanin , Ahmad S. Kodous , Mohammed Aufy , Maha O. Mahmoud , Islam M. Adel , Mohamed A. El-Nabarawi , Eman Abdelhakeem

Griseofulvin, a potent antifungal drug, has recently demonstrated potential anticancer activity in mammalian cancer cells. This study aims to comprehensively investigate the anti-cancer potential of griseofulvin encapsulated into nanospanlastics, focusing on enhanced cellular uptake, selectivity, and robust activation of multiple apoptotic pathways. Griseofulvin nanospanlastics were fabricated using a 2³ full factorial experimental design with Span 60 as the non-ionic surfactant and Tween 80 as the edge activator. Nanospanlastics were characterized for vesicle size, size distribution, zeta potential, and entrapment efficiency. The statistically optimized formulation was selected for further physical characterization and investigation of its anticancer potential via cytotoxicity, selectivity assays, and analysis of molecular pathways (p53, Bax/Bcl-2, caspase 3, pAKT, VEGFR2, ROS). The optimized formulation exhibited circular morphology without any aggregation, 143.5±15.56 nm vesicle size, 0.739±0.021 size distribution, -30±0.99 mV zeta potential, 89.07±0.11 % entrapment efficiency, and 30.2±0.14 g deformability index. In vitro drug release showed an improved drug dissolution rate, critical for cellular uptake. The optimized formulation attained exceptional therapeutic activity with a 2.29-fold improvement in cytotoxicity and an 8.1-fold enhancement in cancer cell selectivity compared to the free drug solution, while simultaneously modulating critical molecular pathways including p53 activation, Bax/Bcl-2, caspase 3, phosphorylated AKT (pAKT) inhibition, and VEGFR2. Most surprisingly, the study revealed an unexpected reduction in reactive oxygen species (ROS) levels, challenging conventional therapeutic paradigms and highlighting novel "redox paradox" mechanisms in cancer treatment. This comprehensive investigation highlights the remarkable apoptotic potential of nanosized griseofulvin, driven by enhanced cellular uptake, superior selectivity, and robust activation of multiple apoptotic pathways.

灰黄霉素是一种有效的抗真菌药物，最近在哺乳动物癌细胞中显示出潜在的抗癌活性。本研究旨在全面研究包裹在纳米塑料中的灰黄霉素的抗癌潜力，重点是增强细胞摄取，选择性和多种凋亡途径的强大激活。采用23全因子实验设计，以Span 60为非离子表面活性剂，Tween 80为边缘活化剂制备灰黄霉素纳米塑料。表征了纳米塑料的囊泡大小、粒径分布、zeta电位和包封效率。通过细胞毒性、选择性试验和分子通路（p53、Bax/Bcl-2、caspase 3、pAKT、VEGFR2、ROS）分析，选择统计优化后的配方进行进一步的物理表征和抗癌潜力研究。优化后的配方形貌为无聚集的圆形，囊泡大小为143.5±15.56 nm，粒径分布为0.739±0.021，zeta电位为-30±0.99 mV，包封效率为89.07±0.11%，可变形指数为30.2±0.14 g。体外药物释放显示出药物溶出率的提高，这对细胞摄取至关重要。与游离药物溶液相比，优化后的配方获得了卓越的治疗活性，细胞毒性提高了2.29倍，癌细胞选择性提高了8.1倍，同时调节了关键的分子途径，包括p53激活、Bax/Bcl-2、caspase 3、磷酸化AKT （pAKT）抑制和VEGFR2。最令人惊讶的是，该研究揭示了活性氧（ROS）水平的意外降低，挑战了传统的治疗范式，并突出了癌症治疗中新的“氧化还原悖论”机制。这项全面的研究强调了纳米灰黄霉素显著的细胞凋亡潜力，它被增强的细胞摄取、优越的选择性和多种凋亡途径的强大激活所驱动。

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引用次数: 0

Systematic optimisation of carrier particle geometry in interactive powder mixtures via a parametric design approach using Bayesian optimisation 通过使用贝叶斯优化的参数化设计方法，系统地优化相互作用粉末混合物中的载体粒子几何形状。

IF 4.7 3区医学 Q1 PHARMACOLOGY & PHARMACY

European Journal of Pharmaceutical Sciences

Pub Date : 2026-01-15 DOI: 10.1016/j.ejps.2026.107442

Melvin Wostry , Regina Scherließ

In this study, a systematic approach for improving the carrier particle geometry in interactive mixtures was conducted. For the evaluation of the geometries, an in-silico model was used, which allowed the creation of a carrier particle loaded with drug particles and to investigate the crucial detachment of the latter in two different kinds of collision simulations. The carrier particle geometries were created with a parametric design tool that enabled continuous modification of the geometry. Data evaluation was performed with a Bayesian Optimisation, which could suggest potentially interesting new geometry modifications based on the evaluated results. The whole setup was implemented as a fully automated process. Particle geometry creation, procession of new geometries in the simulation software and evaluation of the results, including the setup of the following iterations, was performed by precise communication between the different software applications. As a result, it could be demonstrated that the systematic modification of the geometries improved performance in terms of drug detachment. Furthermore, characteristic geometry features responsible for the detachment could be identified.

在这项研究中，提出了一种系统的方法来改善相互作用混合物中载流子粒子的几何形状。为了评估几何形状，使用了一个硅模型，该模型允许创建装载药物颗粒的载体粒子，并在两种不同类型的碰撞模拟中研究后者的关键分离。载体粒子几何形状是通过参数化设计工具创建的，该工具可以连续修改几何形状。数据评估使用贝叶斯优化（Bayesian optimization）进行，该优化可以根据评估结果提出潜在有趣的新几何修改。整个设置是作为一个完全自动化的过程实现的。通过不同的软件应用程序之间的精确通信，完成了粒子几何的创建、模拟软件中新几何的处理和结果的评估，包括后续迭代的设置。因此，可以证明，系统的修改几何形状提高性能方面的药物脱离。此外，还可以识别出导致分离的特征几何特征。

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引用次数: 0

Implementing printing technology in hospital pharmacy preparation – An interview study on opportunities and challenges from medicines authorities’ perspective 在医院制剂中实施印刷技术——从药品主管部门的角度对机遇和挑战的访谈研究。

IF 4.7 3区医学 Q1 PHARMACOLOGY & PHARMACY

European Journal of Pharmaceutical Sciences

Pub Date : 2026-01-15 DOI: 10.1016/j.ejps.2026.107445

Maria Rautamo , Hanna M. Tolonen , Viivi Peltoniemi , Mia Sivén

Advances in three-dimensional (3D) printing technologies have created new possibilities for pharmaceutical manufacturing in hospital setting. One of the key attributes of various 3D printing methods is their capacity for customisation, which benefit patients who require individualised doses and dosage forms. However, the regulatory landscape in Europe regarding 3D printing of pharmaceuticals remains unclear.

This study aimed to (1) survey the perceptions of European medicines authorities regarding the implementation of 3D printing technology in hospital setting, (2) assess the manufacturing process and quality considerations that influence the adoption of the new technology from regulatory standpoint and (3) examine practical collaboration models between hospital pharmacies acting as dosage form manufacturers and pharmaceutical companies acting as suppliers of equipment, material, intermediate and/or product and process development.

A subset of European medicines authorities (n = 5/27) participated in semi-structured interviews, which were guided by three predefined scenarios describing potential approaches to implementing 3D printing in hospital settings. The collected data were analysed using qualitative content analysis.

3D printing was seen as a transformative advancement in pharmaceutical manufacturing. The potential in the production of personalised medicine was identified as a valuable opportunity, whereas the primary concerns pertained the safety and quality of 3D printed pharmaceuticals. Despite the challenges in recruiting the participants, this research highlights the need for more explicit regulatory guidelines and measures to establish robust quality control that ensure the safety and efficacy of the finished products.

三维（3D）打印技术的进步为医院环境中的药品制造创造了新的可能性。各种3D打印方法的关键属性之一是它们的定制能力，这使需要个性化剂量和剂型的患者受益。然而，欧洲关于药品3D打印的监管格局仍不明朗。本研究旨在(1)调查欧洲药品监管机构对在医院环境中实施3D打印技术的看法，(2)从监管角度评估影响新技术采用的制造过程和质量考虑因素，以及(3)检查作为剂型制造商的医院药房与作为设备、材料、医药公司供应商的制药公司之间的实际合作模式。中间和/或产品和工艺开发。一部分欧洲药品管理局（n=5/27）参加了半结构化访谈，访谈由三个预定义的场景指导，这些场景描述了在医院环境中实施3D打印的潜在方法。采用定性内容分析法对收集的资料进行分析。3D打印被视为制药行业的革命性进步。个性化药品生产的潜力被认为是一个宝贵的机会，而主要关注的是3D打印药品的安全性和质量。尽管在招募参与者方面存在挑战，但本研究强调需要更明确的监管指导方针和措施来建立健全的质量控制，以确保成品的安全性和有效性。

{"title":"Implementing printing technology in hospital pharmacy preparation – An interview study on opportunities and challenges from medicines authorities’ perspective","authors":"Maria Rautamo , Hanna M. Tolonen , Viivi Peltoniemi , Mia Sivén","doi":"10.1016/j.ejps.2026.107445","DOIUrl":"10.1016/j.ejps.2026.107445","url":null,"abstract":"<div><div>Advances in three-dimensional (3D) printing technologies have created new possibilities for pharmaceutical manufacturing in hospital setting. One of the key attributes of various 3D printing methods is their capacity for customisation, which benefit patients who require individualised doses and dosage forms. However, the regulatory landscape in Europe regarding 3D printing of pharmaceuticals remains unclear.</div><div>This study aimed to (1) survey the perceptions of European medicines authorities regarding the implementation of 3D printing technology in hospital setting, (2) assess the manufacturing process and quality considerations that influence the adoption of the new technology from regulatory standpoint and (3) examine practical collaboration models between hospital pharmacies acting as dosage form manufacturers and pharmaceutical companies acting as suppliers of equipment, material, intermediate and/or product and process development.</div><div>A subset of European medicines authorities (<em>n</em> = 5/27) participated in semi-structured interviews, which were guided by three predefined scenarios describing potential approaches to implementing 3D printing in hospital settings. The collected data were analysed using qualitative content analysis.</div><div>3D printing was seen as a transformative advancement in pharmaceutical manufacturing. The potential in the production of personalised medicine was identified as a valuable opportunity, whereas the primary concerns pertained the safety and quality of 3D printed pharmaceuticals. Despite the challenges in recruiting the participants, this research highlights the need for more explicit regulatory guidelines and measures to establish robust quality control that ensure the safety and efficacy of the finished products.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"218 ","pages":"Article 107445"},"PeriodicalIF":4.7,"publicationDate":"2026-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145994340","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}

引用次数: 0

In vivo evidence of functional OATP2B1 activity in human skeletal muscle using [11C]erlotinib PET [11C]厄洛替尼PET在人体骨骼肌中功能性OATP2B1活性的体内证据。

IF 4.7 3区医学 Q1 PHARMACOLOGY & PHARMACY

European Journal of Pharmaceutical Sciences

Pub Date : 2026-01-14 DOI: 10.1016/j.ejps.2026.107441

Matthias Jackwerth , Severin Mairinger , Marcus Hacker , Nicolas Tournier , Markus Zeitlinger , Oliver Langer

Organic anion-transporting polypeptide 2B1 (OATP2B1/SLCO2B1) is an uptake transporter expressed in the liver and in several extrahepatic tissues, including skeletal muscle. Muscular OATP2B1 is thought to facilitate intracellular accumulation of statins, potentially contributing to statin-induced myotoxicity. To investigate functional OATP2B1 activity in vivo in human skeletal muscle, we performed positron emission tomography (PET) with the radiolabelled OATP2B1 substrate [¹¹C]erlotinib. Nine healthy male volunteers (age: 31 ± 9 years) underwent two dynamic 60-min PET scans of the head with concurrent arterial blood sampling following intravenous injection of a microdose of [¹¹C]erlotinib (< 10 µg). The first scan was performed without any pharmacological pre-treatment (baseline scan), whereas the second scan was performed after pre-treatment with a single oral dose of unlabelled erlotinib (650 mg), administered 3.0 ± 0.1 h before the start of the PET scan. Volumes of interest (VOIs) were manually delineated for the right and left temporal muscle surrounding the skull on co-registered PET/magnetic resonance imaging (MRI) data and averaged to generate a global temporal muscle VOI. Time-activity curves for temporal muscle and arterial plasma were analysed using a 1-tissue-2-rate constant (1T2K) compartment model and Logan graphical analysis to estimate the total volume of distribution (V_T) of [¹¹C]erlotinib (reflecting the steady-state muscle-to-plasma concentration ratio), as well as the rate constants for transfer of [¹¹C]erlotinib from plasma to muscle (K₁) and from muscle to plasma (k₂). Both Logan analysis and the 1T2K model demonstrated a significant reduction in V_T after erlotinib pre-treatment compared with baseline (V_{T Logan}: baseline: 0.85 ± 0.11 mL/cm³, erlotinib: 0.70 ± 0.08 mL/cm³, −18 ± 8%, p = 0.00047; V_{T 1T2K}: baseline: 0.83 ± 0.11 mL/cm³, erlotinib: 0.67 ± 0.07 mL/cm³, −18 ± 7%, p = 0.00033). K₁ showed a trend toward reduction after erlotinib pre-treatment without reaching statistical significance, whereas k₂ remained unchanged. Our findings demonstrate saturable distribution of [¹¹C]erlotinib to human skeletal muscle, consistent with functional OATP2B1 activity. These results support a mechanistic role for muscular OATP2B1 in statin-induced myotoxicity and highlight its potential broader relevance for the safety and pharmacology of other OATP2B1 substrate drugs.

有机阴离子转运多肽2B1 （OATP2B1/SLCO2B1）是肝脏和一些肝外组织（包括骨骼肌）中表达的摄取转运蛋白。肌肉OATP2B1被认为促进他汀类药物在细胞内的积累，可能导致他汀类药物诱导的肌肉毒性。为了研究体内人体骨骼肌中OATP2B1的功能性活性，我们使用放射性标记的OATP2B1底物[11C]厄洛替尼进行了正电子发射断层扫描（PET）。9名健康男性志愿者（年龄：31±9岁）在静脉注射微剂量[11C]厄洛替尼（< 10µg）后，进行了两次动态60分钟的头部PET扫描，同时进行了动脉采血。第一次扫描在没有任何药物预处理（基线扫描）的情况下进行，而第二次扫描在PET扫描开始前3.0±0.1小时口服单剂量未标记厄洛替尼（650 mg）进行预处理后进行。在共同注册的PET/磁共振成像（MRI）数据上，手动划定头骨周围左右颞肌的兴趣体积（VOI），并进行平均以生成全局颞肌VOI。使用1-组织-2-速率常数（1T2K）室室模型和Logan图形分析分析颞肌和动脉血浆的时间-活动曲线，以估计[11C]厄洛替尼的总分布体积（VT）（反映稳态肌肉-血浆浓度比），以及[11C]厄洛替尼从血浆转移到肌肉（K1）和从肌肉转移到血浆（k2）的速率常数。Logan分析和1T2K模型均显示，与基线相比，埃洛替尼预处理后VT显著降低（VT Logan：基线：0.85±0.11 mL/cm3，埃洛替尼：0.70±0.08 mL/cm3, -18±8%,p = 0.00047；VT 1T2K：基线：0.83±0.11 mL/cm3，埃洛替尼：0.67±0.07 mL/cm3, -18±7%,p = 0.00033）。经厄洛替尼预处理后，K1有降低的趋势，但未达到统计学意义，而k2保持不变。我们的研究结果表明，[¹¹C]厄洛替尼在人类骨骼肌中的饱和分布与OATP2B1的功能性活性一致。这些结果支持了肌肉OATP2B1在他汀类药物诱导的肌肉毒性中的机制作用，并强调了其与其他OATP2B1底物药物的安全性和药理学的潜在广泛相关性。

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引用次数: 0