European Journal of Pharmaceutics and Biopharmaceutics最新文献_第7页

Nanoparticle-based oral rinses for plaque control: A systematic review of efficacy and safety 纳米颗粒口腔冲洗剂用于菌斑控制：有效性和安全性的系统评价。

IF 4.3 2区医学 Q1 PHARMACOLOGY & PHARMACY

European Journal of Pharmaceutics and Biopharmaceutics

Pub Date : 2025-10-30 DOI: 10.1016/j.ejpb.2025.114910

Bakr Ahmed , Fatima Ahmed , Anil Kumar , Mohammad Imran , Mohammad Kashif Iqubal , Hadeel Adel Al-Lami

This systematic review analyzes clinical, preclinical, and patent literature on nano-enabled mouthwashes for plaque control. Searches were conducted across PubMed, Embase, Scopus, Web of Science, and three patent databases (Google Patents, Lens, and Espacenet) for English-language records published from January 2018 to June 2025. Eligible studies included randomized controlled trials (RCTs), other human investigations, and in vitro, ex vivo, or animal studies evaluating nanoparticle-based mouthrinses. Two reviewers independently extracted data, assessed bias risk using the RoB-2 tool, and rated evidence certainty with the GRADE approach. Findings were narratively summarized due to methodological differences. A total of 38 records met the inclusion criteria: 25 primary research studies (10 RCTs; 15 in vitro/animal) and 13 patents on nano-enabled mouthwashes. Silver nanoparticles were the most studied, followed by zinc oxide, titanium dioxide, calcium phosphate, and herbal nanoemulsions. Nano-enabled mouthwashes reduced plaque index by a pooled mean difference of 0.32 (95 % CI: 0.25 to 0.39; I² = 45 %) and gingival index by a pooled mean difference of 0.27 (95 % CI: 0.21 to 0.33; I² = 50 %) units, respectively, comparable to 0.12 % chlorhexidine (CHX), with fewer reports of staining or taste changes. Nanosilver rinses decreased white-spot lesions in orthodontic patients by 66 %, and titanium dioxide-based rinses halved dentine hypersensitivity scores. Preclinical studies showed ≥2-log reductions in biofilm viability, pH-triggered mineral release, and nanozyme-like catalytic activity. Thirteen patents (2003-2024) described stable nanoformulations, odour-neutralizing systems, mucoadhesive carriers, and theranostic technologies, indicating significant commercial interest. Evidence certainty was moderate for short-term plaque and gingival control but low for caries prevention and long-term safety. Nano-enabled mouthwashes show promise as alternatives to CHX, but large, long-term RCTs are needed to confirm efficacy, monitor safety, and support clinical use.

本系统综述分析了纳米漱口水用于菌斑控制的临床、临床前和专利文献。检索了PubMed、Embase、Scopus、Web of Science和三个专利数据库（谷歌Patents、Lens和Espacenet），检索了2018年1月至2025年6月期间发表的英语记录。符合条件的研究包括随机对照试验（rct）、其他人体研究以及评估纳米颗粒口腔清洁的体外、离体或动物研究。两位审稿人独立提取数据，使用rob2工具评估偏倚风险，并使用GRADE方法对证据确定性进行评级。由于方法上的差异，研究结果被叙述总结。共有38项记录符合纳入标准：25项初步研究（10项随机对照试验，15项体外/动物试验）和13项纳米漱口水专利。研究最多的是银纳米粒子，其次是氧化锌、二氧化钛、磷酸钙和草药纳米乳液。纳米漱口水减少菌斑指数池平均差的0.32(95 % CI: 0.25 - 0.39; I2 = 45 %)和牙龈指数池平均差为0.27(95 % CI: 0.21 - 0.33; I2 = 50 %)单位,分别相当于0.12 %洗必泰(CHX),用更少的染色或味道变化的报告。纳米银漱口水使正畸患者的白斑病变减少66% %，二氧化钛漱口水使牙本质过敏评分减半。临床前研究显示 生物膜活力、ph触发的矿物质释放和纳米酶样催化活性降低≥2 log。13项专利（2003-2024）描述了稳定的纳米配方、气味中和系统、黏合剂载体和治疗技术，表明了重大的商业利益。证据确定性在短期菌斑和牙龈控制方面中等，但在预防龋齿和长期安全性方面较低。纳米漱口水显示出作为CHX替代品的潜力，但需要大规模、长期的随机对照试验来确认其有效性、监测安全性并支持临床使用。

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引用次数: 0

Development of Trastuzumab-coupled, siRNA encapsulating mPolyplexes targeting HER2 overexpressing cancer cells 靶向HER2过表达癌细胞的曲妥珠单抗偶联siRNA封装复合物的开发

IF 4.3 2区医学 Q1 PHARMACOLOGY & PHARMACY

European Journal of Pharmaceutics and Biopharmaceutics

Pub Date : 2025-10-28 DOI: 10.1016/j.ejpb.2025.114904

Joschka T. Müller , Salvatore Caruso , Anny Nguyen , David C. Jürgens , Adrian P.E. Kromer , Sahana Sheshachala , Nathan B.P. Adams , Olivia M. Merkel

Over the past decades, significant advancements have been made in various medical fields; however, ovarian cancer (OC) remains inadequately addressed, predominantly relying on relatively toxic cytostatic treatments. In this study, we applied newly developed poly(β-amino) esters (PBAEs) for siRNA delivery. As recent literature has shown, the introduction of a hydrophobic, unsaturated fatty acid together with polycationic spermines as the PBAE side chains are leading to a favourable transfection efficiency, and the resulting materials form a unique class of micelleplexes, termed micelle-embedded polyplexes (mPolyplexes). Here, such mPolyplexes were modified post-particle formation with the approved monoclonal antibody Trastuzumab for HER2 targeting, as supported by a receptor binding analysis through fluorescence shift assay. Physicochemical analysis revealed suitable hydrodynamic diameters of modified mPolyplexes, as determined by dynamic light scattering. Improved cellular uptake when targeted with Trastuzumab was optimized by applying Design of Experiment (DoE). We demonstrated superior gene silencing efficiency of EGFR as well as PLK1, both involved in OC progression, with knockdown values exceeding 82% and 70%, respectively. These findings were corroborated by a relevant cell migration assay. The macroscopic impact after PLK1 silencing on epithelial-mesenchymal transition (EMT) was visualized using confocal microscopy. This work addresses critical questions in the field of ovarian cancer therapy and confirms the suitability of siRNA encapsulating PBAE nanocarriers as promising non-viral vectors.

在过去的几十年里，在各个医学领域取得了重大进展；然而，卵巢癌（OC）仍然没有得到充分解决，主要依赖于相对毒性的细胞抑制剂治疗。在这项研究中，我们使用新开发的聚β-氨基酯（PBAEs）来递送siRNA。正如最近的文献所示，引入疏水不饱和脂肪酸和聚阳离子精胺作为PBAE侧链导致了良好的转染效率，并且所得到的材料形成了一类独特的胶束复合物，称为胶束嵌入复合物（mPolyplexes）。在这里，这种mPolyplexes是用经批准的靶向HER2的单克隆抗体曲妥珠单抗修饰后颗粒形成的，并通过荧光位移法进行受体结合分析。物理化学分析表明，通过动态光散射确定了改性复合材料合适的流体动力直径。应用实验设计（DoE）优化了曲妥珠单抗靶向时细胞摄取的改善。我们证明了EGFR和PLK1具有优越的基因沉默效率，它们都与OC进展有关，敲除值分别超过82%和70%。相关的细胞迁移实验证实了这些发现。用共聚焦显微镜观察PLK1沉默后对上皮-间质转化（EMT）的宏观影响。这项工作解决了卵巢癌治疗领域的关键问题，并证实了siRNA包封PBAE纳米载体作为有前途的非病毒载体的适用性。

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引用次数: 0

Optimization of intranasal trifluoperazine/SPION-leciplex thermosensitive organogel for depression therapy: Pharmacodynamic and pharmacokinetic comparison of magnet placement effects on brain versus nose 鼻内三氟拉嗪/SPION-leciplex热敏有机凝胶治疗抑郁症的优化：脑与鼻磁铁放置效果的药效学和药代动力学比较。

IF 4.3 2区医学 Q1 PHARMACOLOGY & PHARMACY

European Journal of Pharmaceutics and Biopharmaceutics

Pub Date : 2025-10-28 DOI: 10.1016/j.ejpb.2025.114909

Soha Elsalhy , Hanan Refai , Dina A. Osman , Nesrine El Sayed , Maha K.A. Khalifa

Trifluoperazine (TFP), an antipsychotic used in depression management, suffers from extensive first-pass metabolism and poor oral bioavailability. Intranasal delivery offers a promising non-invasive route for direct nose-to-brain targeting, while magnetic nanoparticles can further enhance drug localization and absorption.

This study aimed to optimize and evaluate a superparamagnetic iron oxide nanoparticle (SPION)-loaded leciplex organogel for intranasal delivery of TFP, with emphasis on the effect of external magnet location. The study compared magnet application on the brain to promote olfactory targeting versus on the nose to enhance systemic absorption.

TFP/SPION-leciplex nanoparticles were optimized and incorporated into a thermosensitive mucoadhesive organogel. Pharmacodynamic efficacy was assessed via the forced swimming test, and pharmacokinetics were determined in plasma and brain across four groups: no magnet, magnet on nose, magnet on brain, and oral marketed product.

The optimized formulation (266.20 nm, +50.9 mV, 5.90 emu/g, IC₅₀ 393.92 μg/ml) showed safety and favorable characteristics. Both magnet-assisted groups significantly reduced immobility time versus the non-magnet and oral controls, with no significant difference between the two strategies. However, the “magnet on nose” group achieved the highest plasma levels, favoring systemic absorption, while the “magnet on brain” group achieved the highest brain levels, favoring olfactory targeting.

The SPION-loaded leciplex organogel significantly improved intranasal TFP delivery, enabling dose reduction and superior efficacy compared with oral therapy. Magnet placement was profound in directing drug distribution toward systemic circulation or brain, suggesting that the two approaches may be clinically tailored—“magnet on nose” for systemic delivery and “magnet on brain” for CNS targeting.

三氟拉嗪（TFP）是一种用于抑郁症治疗的抗精神病药物，其首过代谢广泛且口服生物利用度差。鼻内给药为直接从鼻子到大脑靶向提供了一种有前途的无创途径，而磁性纳米颗粒可以进一步增强药物的定位和吸收。本研究旨在优化和评估一种负载超顺磁性氧化铁纳米颗粒（SPION）的有机凝胶用于鼻内给药TFP，并重点研究了外磁体定位的影响。这项研究比较了在大脑上应用磁铁来促进嗅觉靶向和在鼻子上应用磁铁来增强全身吸收。优化了TFP/SPION-leciplex纳米颗粒，并将其掺入热敏黏附有机凝胶中。通过强制游泳试验评估药效学效果，并在血浆和脑内测定药代动力学，分为四组：无磁铁组、鼻上磁铁组、脑上磁铁组和口服上市产品组。优化后的配方（266.20 nm, +50.9 mV, 5.90 emu/g, IC50 393.92 μg/ml）具有良好的安全性。与非磁铁组和口服组相比，磁铁辅助组显著减少了静止时间，两种策略之间无显著差异。然而，“鼻子上的磁铁”组的血浆水平最高，有利于全身吸收，而“大脑上的磁铁”组的大脑水平最高，有利于嗅觉靶向。与口服治疗相比，spion负载的卵磷脂有机凝胶显著改善了鼻内TFP的递送，使剂量减少，疗效优越。磁铁放置在引导药物向体循环或脑部分布方面意义深远，这表明两种方法在临床上可能是量身定制的——“鼻上磁铁”用于全身给药，“脑上磁铁”用于中枢神经系统靶向。

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引用次数: 0

Development of media simulating the properties of human peritoneal fluid and verification of its bio-relevance 模拟人体腹膜液特性的介质的开发及其生物相关性的验证。

IF 4.3 2区医学 Q1 PHARMACOLOGY & PHARMACY

European Journal of Pharmaceutics and Biopharmaceutics

Pub Date : 2025-10-27 DOI: 10.1016/j.ejpb.2025.114908

Magdy M. Abdelquader , Shu Li , Gavin P. Andrews , David S. Jones

Intraperitoneal drug delivery offers a promising strategy for localized treatment of peritoneal tumours and post-surgical wound care. To control drug release profiles, drugs are often embedded within peritoneal implants or delivery devices. Typically, release studies from these devices are performed in phosphate-buffered saline (PBS), which underestimates in vivo release due to its lower drug solubility compared to human peritoneal fluid (hPF). Adding surfactants or albumin alone does not replicate the complexity of hPF, and few studies have addressed the development of a simulated peritoneal fluid (sPF). Accordingly, this study aimed to develop a biorelevant sPF based on hPF composition and to evaluate its ability to mimic hPF. The developed formulation contained salts, glucose, albumin, phosphatidylcholine stabilized by cholesterol and surfactants. The physicochemical properties (pH, buffering capacity, osmolality, wettability, and flow) of the formed fluid were assessed alongside conducting solubility studies of five model drugs with diverse ionization status (acids, bases, and neutral species) in sPF, hPF, and PBS. The results demonstrated that PBS underperformed relative to hPF, while sPF closely matched hPF in buffering capacity, osmolality, flow behaviour, solubilization of the model drugs, and wetting ability. These findings support the use of sPF as a biorelevant medium for solubility and release studies of intraperitoneal drug delivery systems.

腹腔内给药为腹膜肿瘤的局部治疗和术后伤口护理提供了一种很有前途的策略。为了控制药物释放，通常将药物嵌入腹膜植入物或输送装置中。通常，这些装置的释放研究是在磷酸盐缓冲盐水（PBS）中进行的，由于与人腹膜液（hPF）相比，磷酸盐缓冲盐水的药物溶解度较低，因此低估了体内释放。单独添加表面活性剂或白蛋白并不能复制hPF的复杂性，并且很少有研究涉及模拟腹膜液（sPF）的开发。因此，本研究旨在开发一种基于hPF成分的生物相关sPF，并评估其模拟hPF的能力。该配方含有盐、葡萄糖、白蛋白、由胆固醇和表面活性剂稳定的磷脂酰胆碱。在对具有不同电离状态（酸、碱和中性物质）的五种模型药物在sPF、hPF和PBS中的溶解度进行研究的同时，对形成的液体的物理化学性质（pH值、缓冲能力、渗透压、润湿性和流动性）进行了评估。结果表明，PBS相对于hPF表现不佳，而sPF在缓冲能力、渗透压、流动行为、模型药物的溶解性和润湿能力方面与hPF非常接近。这些发现支持将sPF作为一种生物相关介质用于腹腔内给药系统的溶解度和释放研究。

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引用次数: 0

Mucus-penetrating archaeolipid nanocarriers delivering Thymus vulgaris essential oil and tobramycin: A multifunctional approach against Pseudomonas aeruginosa biofilms and inflammation 渗透黏液的始祖脂纳米载体递送寻常胸腺精油和妥布霉素：一种抗铜绿假单胞菌生物膜和炎症的多功能方法。

IF 4.3 2区医学 Q1 PHARMACOLOGY & PHARMACY

European Journal of Pharmaceutics and Biopharmaceutics

Pub Date : 2025-10-26 DOI: 10.1016/j.ejpb.2025.114906

Noelia Perez , Milagros Velurtas , Patricia C. Rivas Rojas , María Jose Morilla , Eder L. Romero , Ana Paula Perez

Cystic fibrosis (CF) is characterized by thick mucus obstruction, persistent Pseudomonas aeruginosa biofilms, and chronic airway inflammation, leading to progressive lung damage. Inhaled tobramycin (TB) is the standard antibiotic therapy but has limited efficacy due to poor biofilm penetration and bacterial tolerance, while Thymus vulgaris essential oil (EOT) provides antioxidant and anti-inflammatory effects but is hindered by low solubility and instability. In this study, a comprehensive in vitro evaluation was conducted on EOT and TB co-loaded into nanostructured archaeolipid carriers (NAL-EOT/TB), composed of a compritol–miglyol lipid matrix with a surface coating of Tween 80 and archaeolipids from the archaea Halorubrum tebenquichense. NAL-EOT/TB interacted minimally with mucins and diffused efficiently through artificial mucus. Under mucus-covered conditions, macrophage uptake was higher for NAL-EOT/TB than for non-archaeolipid nanocarriers (NLC-EOT/TB), likely due to improved mucus permeation and scavenger receptor recognition. In epithelial cell–biofilm co-cultures, NAL-EOT/TB significantly decreased epithelial cell damage compared to both free EOT/TB and NLC-EOT/TB. Moreover, NAL-EOT/TB lowered ROS in neutrophil-like cells and achieved greater IL-8 reduction than dexamethasone. These findings support NAL-EOT/TB as a multifunctional nanotherapeutic platform to address mucus penetration, biofilm disruption, and airway inflammation in CF.

囊性纤维化（CF）以粘稠的粘液阻塞、持续的铜绿假单胞菌生物膜和慢性气道炎症为特征，导致进行性肺损伤。吸入妥布霉素（TB）是标准的抗生素治疗方法，但由于生物膜渗透性差和细菌耐受性差，其疗效有限，而寻常胸腺精油（EOT）具有抗氧化和抗炎作用，但由于溶解度低和不稳定性而受到阻碍。本研究对EOT和TB共载于纳米结构的古脂肪载体（NAL-EOT/TB）进行了体外综合评价。纳米结构的古脂肪载体（NAL-EOT/TB）由表面涂覆t80的合成醇- migolol脂质基质和来自tebenquicense的古细菌的古脂肪组成。NAL-EOT/TB与黏液相互作用最小，通过人工黏液有效扩散。在黏液覆盖的条件下，NLC-EOT/TB的巨噬细胞摄取高于非考古脂质纳米载体（NLC-EOT/TB），这可能是由于黏液渗透和清除剂受体识别的改善。在上皮细胞-生物膜共培养中，与游离EOT/TB和NLC-EOT/TB相比，NAL-EOT/TB显著降低了上皮细胞损伤。此外，NAL-EOT/TB降低了中性粒细胞样细胞中的ROS，并且比地塞米松更能降低IL-8。这些发现支持NAL-EOT/TB作为一个多功能纳米治疗平台来解决CF中的粘液渗透、生物膜破坏和气道炎症。

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引用次数: 0

Deciphering protein aggregation in freeze-thaw process: the roles of cold denaturation and shear stress 冻融过程中蛋白质聚集的解译：冷变性和剪切应力的作用

IF 4.3 2区医学 Q1 PHARMACOLOGY & PHARMACY

European Journal of Pharmaceutics and Biopharmaceutics

Pub Date : 2025-10-25 DOI: 10.1016/j.ejpb.2025.114905

Miguel Â. Rodrigues , Andreia Duarte , Rafaela Neves , Vítor Geraldes , Klara Gries , Michael Schupfner , Sebastian Andris

Understanding protein aggregation during freeze–thaw is vital for biopharmaceutical quality assurance. This study investigates monoclonal antibody aggregation linked to stress-time, the time a formulation remains partly frozen above glass transition temperature of the freeze concentrate (T_g’). Stress–time distributions of a 0.5 L bottle were implemented in 10 mL vials by controlling ice-nucleation, cooling, and heating rates. These vials were used as downscale models to explore cold denaturation, by varying times under temperatures from −5 °C to T_g’. Matching stress-times between scales resulted in similar aggregation levels. However, extending the stress-time in a low cold denaturation range (−5 °C to freezing equilibrium temperature (T_f)) did not significantly increase aggregation, suggesting its critical role in freeze–thaw stability. Aggregation in vials was about 1/3 lower than in bottles, apparently related to the vials’ bottom-up freezing geometry, which does not enclose unfrozen liquid within the ice. Imposing a similar geometry on the bottle, using top insulation, aligning aggregation levels, suggesting the contribution of shear stress from ice interface percolation. Overall, a 5.5 mL sample (in a 10 mL vial) may serve as a model for larger volumes by accurately controlling heat transfer rates with the assistance of computational fluid dynamics. This approach provides supporting evidence and a step toward improving understanding of biopharmaceutical ‘sensitivity’ to freeze–thaw stresses.

了解蛋白质在冻融过程中的聚集对生物制药质量保证至关重要。本研究调查了单克隆抗体聚集与压力-时间的关系，即配方在冷冻浓缩物的玻璃化转变温度（Tg）以上保持部分冷冻的时间。通过控制冰核、冷却和加热速率，在10ml小瓶中实现0.5 L瓶的应力-时间分布。这些小瓶被用作小规模模型，通过在- 5°C到Tg '的温度下改变时间来探索冷变性。尺度之间匹配的压力时间导致了相似的聚集水平。然而，在低冷变性范围内（- 5°C至冻结平衡温度（Tf））延长应力时间并没有显著增加聚集，表明其在冻融稳定性中起关键作用。小瓶中的聚集比瓶中的低约1/3，显然与小瓶自下而上的冷冻几何形状有关，这种形状没有将未冻的液体包裹在冰内。在瓶子上施加类似的几何形状，使用顶部绝缘，对齐聚集水平，表明来自冰界面渗透的剪切应力的贡献。总体而言，5.5 mL样品（在10 mL小瓶中）可以作为更大体积的模型，通过在计算流体动力学的帮助下精确控制传热速率。这种方法提供了支持性证据，并朝着提高对生物制药对冻融压力的“敏感性”的理解迈出了一步。

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引用次数: 0

Self-assembled rapamycin prodrug nanoparticles for posterior segment targeting and effective treatment of experimental uveitis 自组装雷帕霉素前药纳米颗粒后段靶向和有效治疗实验性葡萄膜炎。

IF 4.3 2区医学 Q1 PHARMACOLOGY & PHARMACY

European Journal of Pharmaceutics and Biopharmaceutics

Pub Date : 2025-10-17 DOI: 10.1016/j.ejpb.2025.114903

Fangming Liang , Yue Wang , Ning Li , YuBo Liu , Yuan Gao , Yinan Song , Zhenzhen Zhao , Yongjun Wang , Hongzhuo Liu

The treatment of posterior uveitis remains challenging due to the need for long-term medication and the limited efficacy of current therapies. In this study, we developed an injectable rapamycin-based nanoparticle formulation designed to extend intraocular residence time and enhance retinal penetration, thereby improving therapeutic outcomes. The nanoparticles were formed via self-assembly of rapamycin conjugated with a hydrophobic alkyl chain, yielding uniformly spherical particles with an average diameter of approximately 90 nm. In vitro experiments confirmed that the formulation exhibited minimal cytotoxicity, potent anti-inflammatory effects, inhibition of endothelial cell migration, and efficient uptake by retinal pigment epithelial (RPE) cells. In vivo imaging demonstrated that the nanoparticles rapidly localized to the RPE layer of the posterior segment following intravitreal injection, in contrast to the free drug. Moreover, experimental autoimmune uveoretinitis (EAU) rats treated with nanoparticles exhibited a substantial alleviation of ocular inflammation and a concomitant reduction in the expression of inflammatory markers, including CD45, CD68, IBA-1, and IL-17.

由于需要长期的药物治疗和目前的治疗效果有限，后葡萄膜炎的治疗仍然具有挑战性。在这项研究中，我们开发了一种可注射的基于雷帕霉素的纳米颗粒配方，旨在延长眼内停留时间，增强视网膜渗透，从而改善治疗效果。通过雷帕霉素与疏水烷基链的自组装形成纳米颗粒，得到均匀的球形颗粒，平均直径约为90 nm。体外实验证实，该制剂具有最小的细胞毒性，有效的抗炎作用，抑制内皮细胞迁移，并被视网膜色素上皮细胞（RPE）有效吸收。体内成像显示，与游离药物相比，玻璃体内注射后，纳米颗粒迅速定位到后段RPE层。此外，用纳米颗粒治疗的实验性自身免疫性葡萄膜视网膜炎（EAU）大鼠表现出眼部炎症的显著缓解，同时炎症标志物的表达减少，包括CD45、CD68、IBA-1和IL-17。

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引用次数: 0

Corrigendum to “Dissolving microneedle patches for delivery of amniotic mesenchymal stem cell metabolite products for skin regeneration in UV-aging induced mice” [Eur. J. Pharm. Biopharm. 204 (2024) 114482] “溶解微针贴片用于输送羊膜间充质干细胞代谢物用于紫外线老化诱导小鼠皮肤再生”的更正[欧洲]。j .制药。生物医学工程学报，2014(4):349 - 349。

IF 4.3 2区医学 Q1 PHARMACOLOGY & PHARMACY

European Journal of Pharmaceutics and Biopharmaceutics

Pub Date : 2025-10-17 DOI: 10.1016/j.ejpb.2025.114896

Andang Miatmoko , Berlian Sarasitha Hariawan , Devy Maulidya Cahyani , Qonita Kurnia Anjani , Febri Annuryanti , Rifda Tarimi Octavia , Djoko Legowo , Kusuma Eko Purwantari , Noorma Rosita , Purwati , Ryan F. Donnelly , Dewi Melani Hariyadi

引用次数: 0

Gas-based therapies in chronic wounds: A scoping review of preclinical and clinical data 慢性伤口的气体疗法：临床前和临床数据的大范围回顾。

IF 4.3 2区医学 Q1 PHARMACOLOGY & PHARMACY

European Journal of Pharmaceutics and Biopharmaceutics

Pub Date : 2025-10-15 DOI: 10.1016/j.ejpb.2025.114894

Srikar Kasha , Sara M. Hanning , Odunayo O. Mugisho , Sachin S. Thakur

Introduction

Chronic wounds are injuries that persist beyond expected healing timeframes. Although they have varying aetiologies abnormal development, prolonged inflammation and evident hypoxia are common features in all chronic wounds. Innovative treatments are sought and gas-based therapies in particular have shown promise in supporting conventional treatment strategies. This scoping review aims to identify and compare the range of formulations that are used for gas-based therapy and evaluate their effectiveness in treating chronic wounds.

Methods

A scoping review was conducted with articles identified from the Medline, Embase and Scopus databases. Articles exploring gas-based therapies in chronic wound healing were identified after screening all the search results against inclusion and exclusion criteria.

Results and Discussion

There were 54 clinical studies and 45 preclinical studies eligible for analysis. Gas-based therapies were delivered by various modalities. Hyperbaric oxygen therapy and topical gas therapies demonstrated some clinical utilisation, though adoption into standard care protocols was limited by costs and variable treatment outcomes. Novel formulations were of significant interest within the preclinical space, with micro- and nanoparticle systems and hydrogel scaffolds demonstrating an ability to effectively deliver various therapeutic gases and improve chronic injury outcomes in cell and animal-based models. However, the wound healing capacities of established and exploratory approaches have rarely been compared to each other.

Conclusions

Hyperbaric oxygen therapy and topical gas therapy are clinically used in chronic wound management, although they have not been adopted as part of standard wound care. A variety of recently developed gas-loaded formulations have demonstrated preclinical potential and are poised to soon migrate into the clinical trial domain.

慢性伤口是指持续超过预期愈合时间的损伤。虽然它们的病因各不相同，但发育异常、长期炎症和明显缺氧是所有慢性伤口的共同特征。人们寻求创新的治疗方法，特别是气体疗法在支持传统治疗策略方面表现出了希望。本综述旨在确定和比较用于气体疗法的配方范围，并评估其治疗慢性伤口的有效性。方法：对从Medline、Embase和Scopus数据库中确定的文章进行范围综述。在对所有检索结果进行纳入和排除标准筛选后，确定了探索气体治疗慢性伤口愈合的文章。结果和讨论：54项临床研究和45项临床前研究符合分析条件。以气体为基础的治疗以各种方式进行。高压氧治疗和局部气体治疗显示了一些临床应用，尽管纳入标准护理方案受到成本和治疗结果的限制。新型制剂在临床前领域引起了极大的兴趣，在细胞和动物模型中，微粒子和纳米粒子系统以及水凝胶支架显示出有效输送各种治疗气体和改善慢性损伤结果的能力。然而，已建立的和探索性方法的伤口愈合能力很少相互比较。结论：高压氧治疗和局部气体治疗在慢性伤口治疗中得到了临床应用，尽管它们尚未被作为标准伤口护理的一部分。最近开发的各种气体负载配方已经显示出临床前潜力，并准备很快进入临床试验领域。

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引用次数: 0

Effects of Co-Processed and conventional excipients on content uniformity 共加工辅料与常规辅料对含量均匀性的影响。

IF 4.3 2区医学 Q1 PHARMACOLOGY & PHARMACY

European Journal of Pharmaceutics and Biopharmaceutics

Pub Date : 2025-10-14 DOI: 10.1016/j.ejpb.2025.114902

Stephanie Stewart , Jenna Reinhard , Anthony Carpanzano , Emil Ciurczak , Gernot Warnke

Silicification of microcrystalline cellulose (MCC) has previously been shown to have positive effects on the powder’s flowability and tabletability compared to plain MCC or physical blends of colloidal silicon dioxide (CSD) and MCC [1]. A further characteristic of silicified MCC (SMCC) is its specific surface area, which is approximately five times larger than that of plain MCC [1]. It was hypothesized, therefore, that SMCC might have beneficial effects in terms of blend and content uniformity via effects of interactive blending.

This study was designed to compare the blending efficacy of silicified microcrystalline cellulose and a co-processed SMCC-based multifunctional excipient to that of physical blends comprising the same nominal components. Near infrared spectroscopy (NIRS) was used to probe blend uniformity during the blending process of the excipients and a model active pharmaceutical ingredient (API), caffeine, presenting morphological and electrostatic challenges with regard to content uniformity. In addition to NIRS, both particle size analysis and scanning electron microscopy (SEM) were used to investigate the resulting blends. Content uniformity on the tableted blends, obtained by caffeine dissolution, was used to investigate the effects of differing blend uniformity on a final oral solid dosage form.

For this non-optimized formulation with a challenging API, use of SMCC and a co-processed SMCC-based multifunctional excipient yielded formulations with significant benefits over using standard MCC, or MCC blended with colloidal silicon dioxide (CSD). These benefits included a faster blend uniformity, prevention of particle attrition, and a reduced impact of blender type and materials. Additionally, use of silicified microcrystalline cellulose yielded formulations with increased tablet hardness and reduced ejection forces.

与普通的微晶纤维素（MCC）或胶体二氧化硅（CSD）和MCC[1]的物理混合物相比，微晶纤维素（MCC）的硅化已被证明对粉末的流动性和可食用性有积极影响。硅化MCC （SMCC）的另一个特点是其比表面积约为普通MCC（[1]）的5倍。因此，我们假设SMCC可能通过交互混合效应在混合和内容均匀性方面产生有益的影响。本研究旨在比较硅化微晶纤维素与共加工的smcc多功能赋形剂的共混效果与包含相同标称成分的物理共混效果。采用近红外光谱（NIRS）对辅料与模型原料药咖啡因共混过程中的共混均匀性进行了检测，发现其含量均匀性存在形态和静电方面的问题。除了近红外光谱外，还使用粒度分析和扫描电子显微镜（SEM）对所得混合物进行了研究。通过咖啡因溶解获得的片剂混合物的含量均匀性，用于研究不同混合均匀性对最终口服固体剂型的影响。对于这种具有挑战性API的非优化配方，使用SMCC和协同加工的基于SMCC的多功能赋形剂产生的配方比使用标准MCC或与胶体二氧化硅（CSD）混合的MCC具有显着的优势。这些好处包括更快的混合均匀性，防止颗粒磨损，减少搅拌机类型和材料的影响。此外，硅化微晶纤维素的使用产生了增加片剂硬度和减少弹射力的配方。

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