European Journal of Pharmaceutics and Biopharmaceutics最新文献_第6页

From physics to prediction: genetic algorithm-optimized neural network using hansen solubility parameters for pharmaceutical solubility in neat and mixed solvents 从物理到预测：遗传算法优化的神经网络，使用汉森溶解度参数用于药物在纯和混合溶剂中的溶解度。

IF 4.3 2区医学 Q1 PHARMACOLOGY & PHARMACY

European Journal of Pharmaceutics and Biopharmaceutics

Pub Date : 2026-02-01 Epub Date: 2025-12-05 DOI: 10.1016/j.ejpb.2025.114954

Hossein Jalaei Salmani , Hamed Karkhanechi , Hamidreza Sadeghifar

Reliable prediction of active pharmaceutical ingredient (API) solubility in complex solvent systems remains challenging. Existing models often sacrifice generalizability for accuracy or have limited applicability due to implementation complexity. The current study presents a practical, streamlined modeling framework requiring only temperature, solvent composition, and Hansen solubility parameters (HSPs) — information that is simple and readily accessible. These parameters serve as inputs for an effective and easy-to-apply model: the multilayer perceptron artificial neural network (MLPANN). Beyond optimizing the network architecture with a genetic algorithm (GA), model accuracy is further supported by six input scenarios designed to explore alternative HSP formulations and dimensional reduction strategies. To ensure generality, the MLPANN was trained on 496 experimental solubility values of acetaminophen, diazepam, ibuprofen, lorazepam, and naproxen in both neat and binary solvent systems, including water, ethanol, isopropanol, dioxane, NMP, and propylene glycol.

Two scenarios, using the optimized networks, achieved R² values exceeding 0.99 across training, validation, and testing subsets. Graphical validation—an important aspect often overlooked in previous studies—demonstrated excellent predictive performance for unseen testing data of acetaminophen in isopropanol–water and naproxen in ethanol–water mixtures.

有效药物成分（API）在复杂溶剂体系中溶解度的可靠预测仍然具有挑战性。现有模型经常为了准确性而牺牲泛化性，或者由于实现的复杂性而具有有限的适用性。目前的研究提出了一个实用的、流线型的建模框架，只需要温度、溶剂组成和汉森溶解度参数（HSPs）——这些信息简单易懂。这些参数作为一个有效且易于应用的模型的输入：多层感知器人工神经网络（MLPANN）。除了使用遗传算法（GA）优化网络架构外，还通过六个输入场景来进一步支持模型的准确性，这些场景旨在探索替代HSP公式和降维策略。为了确保普遍性，MLPANN对对乙酰氨基酚、地西泮、布洛芬、劳拉西泮和萘普生在纯溶剂和二元溶剂体系（包括水、乙醇、异丙醇、二氧六环、NMP和丙二醇）中的496个实验溶解度值进行了训练。在使用优化网络的两个场景中，在训练、验证和测试子集中实现了超过0.99的R2值。图形验证——在以前的研究中经常被忽视的一个重要方面——展示了对异丙醇-水中的对乙酰氨基酚和乙醇-水混合物中的萘普生的未知测试数据的出色预测性能。

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引用次数: 0

3D-printing of lipid formulations: Going slow in a fast-paced field 脂质配方的3d打印：在快节奏的领域中进展缓慢。

IF 4.3 2区医学 Q1 PHARMACOLOGY & PHARMACY

European Journal of Pharmaceutics and Biopharmaceutics

Pub Date : 2026-02-01 Epub Date: 2025-12-15 DOI: 10.1016/j.ejpb.2025.114964

Moaaz Abdelhamid , Dalip Kumar , Martin Spoerk , Sharareh Salar-Behzadi

Lipid-based excipients (LBE) are a crucial class of functional excipients with significant potential for pharmaceutical formulation and product development. The wide variety of molecules in this class provides opportunities for designing novel dosage forms. However, the utilization of LBEs for 3D-printing applications is currently limited, thereby hindering the full potential of lipids and impeding the advancement of 3D-printing technologies. Notably, only a few publications report the 3D-printing of lipid-based formulations. This review provides a detailed discussion and analysis of these publications. It elucidates the revolutionary capabilities of 3D-printing and presents the potential of LBEs as functional pharmaceutical excipients, with a particular focus on 3D-printing applications. Additionally, the review provides an overview of the current challenges from material perspectives and suggests potential future research topics related to LBEs for 3D-printing of personalized medicine.

脂基赋形剂（LBE）是一类重要的功能性赋形剂，在药物配方和产品开发方面具有重要的潜力。本课程中分子的多样性为设计新的剂型提供了机会。然而，LBEs在3d打印应用中的应用目前是有限的，从而阻碍了脂质的全部潜力，阻碍了3d打印技术的进步。值得注意的是，只有少数出版物报道了基于脂质的配方的3d打印。本文对这些出版物进行了详细的讨论和分析。它阐明了3d打印的革命性能力，并展示了LBEs作为功能性药用辅料的潜力，特别关注3d打印应用。此外，该综述从材料的角度概述了当前面临的挑战，并提出了与个性化医疗3d打印LBEs相关的潜在未来研究课题。

引用次数: 0

Development of 3D-printed chitosan/p-coumaric acid scaffolds for wound healing: antibacterial properties and drug release kinetics 3d打印壳聚糖/对香豆酸伤口愈合支架的开发：抗菌性能和药物释放动力学。

IF 4.3 2区医学 Q1 PHARMACOLOGY & PHARMACY

European Journal of Pharmaceutics and Biopharmaceutics

Pub Date : 2026-02-01 Epub Date: 2025-12-05 DOI: 10.1016/j.ejpb.2025.114953

Nouf D. Alshammari , Prateek Uttreja , Rasha Elkanayati , Leela Raghava Jaidev Chakka , Sateesh Kumar Vemula , Michael A. Repka

Para-coumaric acid (P-CA), a plant-derived phenolic compound, exhibits potent antioxidant activity that counteracts oxidative stress, a key factor delaying wound repair. In this study, a novel biocompatible wound healing scaffold was developed by incorporating P-CA into a chitosan-based polymeric matrix using hot-melt extrusion (HME) combined with fused deposition modeling (FDM) 3D printing. Chitosan (CS), polyethylene oxide (PEO), and cryomilled polycaprolactone (PCL) were used to achieve optimal printability and mechanical strength. The physical mixtures were extruded (110 °C, 50 rpm, 2.5 mm die) and printed into scaffolds (20 × 20 × 1 mm, 80 % infill). The optimized formulation, PCL/CS/P-CA/PEO (35:20:10:35, %w/w), produced scaffolds with excellent dimensional accuracy and mechanical integrity. In-vitro drug release studies demonstrated a sustained release of P-CA over three days. Antibacterial testing against Escherichia coli (E.coli) showed no inhibition with PCL/PEO, while CS and P-CA provided moderate activity individually. Notably, their combination yielded the highest antibacterial effect, suggesting a synergistic effect. These results suggest that P-CA-loaded CS-based scaffolds can provide sustained drug delivery with enhanced antibacterial performance, offering promise for wound healing applications.

对香豆酸（P-CA）是一种植物衍生的酚类化合物，具有强大的抗氧化活性，可以抵消氧化应激，这是延迟伤口修复的关键因素。在这项研究中，通过热熔挤压（HME）结合熔融沉积建模（FDM） 3D打印，将P-CA加入到壳聚糖基聚合物基质中，开发了一种新型的生物相容性伤口愈合支架。采用壳聚糖（CS）、聚氧聚乙烯（PEO）和冷磨聚己内酯（PCL）获得最佳的印刷适性和机械强度。物理混合物被挤压(110 °C, 50 rpm, 2.5 毫米死亡)和印刷到支架(20 ×20  ×  1毫米,80 %加密)。优化后的配方为PCL/CS/P-CA/PEO (35:20:10:35, %w/w)，制备的支架具有良好的尺寸精度和机械完整性。体外药物释放研究表明，P-CA的持续释放超过三天。PCL/PEO对大肠杆菌无抑制作用，CS和P-CA对大肠杆菌有中等抑制作用。值得注意的是，它们的组合抗菌效果最高，表明它们具有协同效应。这些结果表明，负载p - ca的CS-based支架可以提供持续的药物递送和增强的抗菌性能，为伤口愈合应用提供了希望。

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引用次数: 0

Simulation of gut motility effect in the USP dissolution apparatus to study drug release in the large intestine 在USP溶出仪中模拟肠道运动效应以研究药物在大肠中的释放。

IF 4.3 2区医学 Q1 PHARMACOLOGY & PHARMACY

European Journal of Pharmaceutics and Biopharmaceutics

Pub Date : 2026-02-01 Epub Date: 2025-12-03 DOI: 10.1016/j.ejpb.2025.114951

Oleksandr Zdoryk , Michael Lanz , Georgios Imanidis

An apparatus was designed and constructed to simulate the effect of large intestinal motility on drug release measurement in vitro, the purpose being to evaluate the influence of implementing gut motility on release rate from matrix tablets intended for controlled colonic delivery. The USP 1 dissolution apparatus was modified by replacing the basket with a bag holder and a mesh bag that contained the dosage form and adding polymer beads inside and outside of the bag in the dissolution vessel (Bag-Beads model). The motility index resulting from contractions of the gut wall was calculated from intraluminal pressure data measured in the large intestine of healthy volunteers with the SmartPill® ingestible telemetric capsule. It was possible to reproduce this motility index in the in vitro Bag-Beads model utilizing the SmartPill® by adjusting the number of beads of appropriate size and density and the rotation rate of the shaft holding the bag. Reproducibility of motility index and drug release measurement was established and a correlation between in vitro motility index and drug release rate was found for matrix tablets consisting of xyloglycan. This is a plant polysaccharide used as matrix former that was demonstrated previously to provide controlled colonic release by the action of bacterial enzymes. Drug release rate in the Bag-Beads model replicating the in vivo motility index was higher than release rate measured in the compendial USP 2 apparatus. This was true for different levels of bacterial xyloglucanase activity. It is concluded that this simulation of motility provides an indication of the effect of large intestinal dynamics on drug release. A comparison of the measured release rate with preclinical in vivo results is discussed, additional data is required, however, for an in vitro – in vivo correlation. The study highlights the potential to simulate the effect of contractile large intestinal activity for better in vitro prediction of drug release and the possibility to develop and optimize colonic targeting formulations under improved biorelevant testing conditions.

设计并构建了模拟大肠运动对体外药物释放测量的影响的实验装置，目的是评估肠道运动对用于控制结肠给药的基质片释放率的影响。USP 1溶出仪的改进方法是，用包含剂型的袋架和网袋替换篮，并在溶出容器中在袋内和袋外添加聚合物微球（袋-微球模型）。通过使用SmartPill®可摄取遥测胶囊在健康志愿者的大肠中测量的腔内压力数据，计算由肠壁收缩引起的运动指数。在含有SmartPill®的体外bag - beads模型中，通过调整适当大小和密度的beads的数量以及持袋轴的旋转速率，可以重现该运动指数。建立了木聚糖基质片的体外运动指数和药物释放度测定的重复性，并发现了体外运动指数与药物释放率的相关性。这是一种用作基质前产物的植物多糖，先前已被证明可通过细菌酶的作用提供受控的结肠释放。复制体内运动指数的Bag-Beads模型的药物释放率高于药典usp2仪器的释放率。这对不同水平的细菌木葡聚糖酶活性是正确的。因此，这种运动模拟提供了大肠动力学对药物释放的影响的指示。比较测量的释放率与临床前体内结果进行了讨论，然而，需要额外的数据，体外-体内的相关性。该研究强调了模拟收缩性大肠活动的影响以更好地体外预测药物释放的潜力，以及在改善的生物相关条件下开发和优化结肠靶向制剂的可能性。

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引用次数: 0

Development of spray-dried phage-aztreonam microparticles for inhalation therapy of Pseudomonas aeruginosa lung infections 雾化干燥噬菌体氮曲南微粒吸入治疗铜绿假单胞菌肺部感染的研制。

IF 4.3 2区医学 Q1 PHARMACOLOGY & PHARMACY

European Journal of Pharmaceutics and Biopharmaceutics

Pub Date : 2026-02-01 Epub Date: 2025-12-15 DOI: 10.1016/j.ejpb.2025.114966

Alexandra Hübl , Johannes Most , Christopher Hauß, Viktoria Planz, Maike Windbergs

Despite considerable efforts in antibiotic therapy, pulmonary infections caused by Pseudomonas aeruginosa remain a major challenge, particularly in diseases such as cystic fibrosis. Bacteriophage-antibiotic combinations have recently emerged as a potential alternative due to synergistic effects and the ability to overcome resistance. However, phage instability and sensitivity continue to hinder clinical translation.

In this study, we developed an inhalable spray-dried microparticle formulation co-encapsulating bacteriophages against P. aeruginosa and the β-lactam antibiotic aztreonam using mannitol, leucine, and trehalose as excipients. The particles exhibited favorable aerosol properties for deep lung delivery (geometric diameter: 1.39 ± 0.11 µm, mass median aerodynamic diameter: 2.42 ± 0.14 µm) and a burst release profile enabling immediate antimicrobial activity. Aztreonam was efficiently encapsulated (97.87 ± 0.91 %), while phage viability could be maintained through processing, remaining stable for 28 days at 4 and −20 °C. Therapeutic efficacy was confirmed by treatment of P. aeruginosa biofilms. A reduction in bacterial load by 99.90 % was achieved within 24 h. Microparticle biocompatibility was demonstrated in vitro using human lung epithelial cells.

The spray-dried phage-aztreonam microparticles enabled phage viability and stability in a formulation and highlight the feasibility of phage-antibiotic co-delivery through dry powder inhalation therapy for treating pulmonary P. aeruginosa infections.

尽管在抗生素治疗方面做出了相当大的努力，但铜绿假单胞菌引起的肺部感染仍然是一个主要挑战，特别是在囊性纤维化等疾病中。由于协同效应和克服耐药性的能力，噬菌体-抗生素组合最近成为一种潜在的替代方案。然而，噬菌体的不稳定性和敏感性仍然阻碍着临床转化。在这项研究中，我们开发了一种可吸入的喷雾干燥微粒制剂，以甘露醇、亮氨酸和海藻糖为辅料，将抗P. aeruginosa和β-内酰胺抗生素aztreonam的噬菌体共包封。颗粒表现出良好的气溶胶特性，有利于肺深部输送（几何直径：1.39 ± 0.11 µm，质量中位数气动直径：2.42 ± 0.14 µm）和突发释放特性，能够立即实现抗菌活性。Aztreonam被高效封装（97.87 ± 0.91 %），通过处理可以保持噬菌体活力，在4和-20 °C下保持28 天的稳定。通过对铜绿假单胞菌生物膜的处理，证实了其治疗效果。在24 h内，细菌负荷减少99.90 %。用人肺上皮细胞体外验证了微粒的生物相容性。喷雾干燥的噬菌体-氮曲南微粒使噬菌体在制剂中具有活力和稳定性，并强调了通过干粉吸入治疗肺部铜绿假单胞菌感染的噬菌体-抗生素共递送的可行性。

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引用次数: 0

Corrigendum to “Enhancement in site-specific delivery of carvacrol for potential treatment of infected wounds using infection responsive nanoparticles loaded into dissolving microneedles: A proof of concept study.” [Eur. J. Pharm. Biopharm. 147 (2020) 57–68] “将感染反应性纳米颗粒装载到溶解性微针中，增强对感染伤口潜在治疗的特定部位的卡维罗的递送：概念验证研究”的更正。(欧元。j .制药。生物医学工程学报，2014(5):557 - 568。

IF 4.3 2区医学 Q1 PHARMACOLOGY & PHARMACY

European Journal of Pharmaceutics and Biopharmaceutics

Pub Date : 2026-01-01 Epub Date: 2025-11-17 DOI: 10.1016/j.ejpb.2025.114927

Maria Mir , Andi Dian Permana , Naveed Ahmed , Gul Majid Khan , Asim ur Rehman , Ryan F. Donnelly

引用次数: 0

In vitro two stage one compartment dumping test data and absorption/formulation PBBM modeling to explain a bioequivalence failure of valsartan formulations 体外两阶段一室倾倒试验数据和吸收/配方PBBM模型来解释缬沙坦配方的生物等效性失败。

IF 4.3 2区医学 Q1 PHARMACOLOGY & PHARMACY

European Journal of Pharmaceutics and Biopharmaceutics

Pub Date : 2026-01-01 Epub Date: 2025-11-17 DOI: 10.1016/j.ejpb.2025.114932

Bárbara Sánchez-Dengra, Alejandro Ruiz-Picazo, Isabel Gonzalez-Alvarez, Marta Gonzalez-Alvarez, Marival Bermejo

Background

In recent years, significant efforts have been made to develop new dissolution methods capable of predicting the in vivo behavior of pharmaceutical formulations. This is essential for establishing valid in vitro-in vivo correlations (IVIVCs) and biopredictive models. However, many of these methodologies involve sophisticated, costly, and complex devices designed to replicate human physiology. The objective of this study was to predict in vivo bioequivalence (BE) using a simplified dynamic dissolution methodology and to establish a physiologically based biopharmaceutics model (PBBM).

Methods

An oral fixed-dose combination of valsartan (VALS, BCS Class IV) and hydrochlorothiazide (HCTZ, BCS Class III) was used for the study. The reference product (Co-Diovan® Forte) and two generic formulations were evaluated using a dissolution approach. A two stage one compartment dissolution technique, known as the “dumping test,” was applied to assess drug release profiles. The in vitro dissolution data obtained were incorporated into the PBBM, with two scaling factors—one for time and another for absorption—to enhance predictive accuracy.

Results

The “dumping test” successfully simulated the different dissolution behaviors of the formulations and explained the failure of bioequivalence in certain cases. The established IVIVC demonstrated both validity and biopredictive capability. The percentage prediction errors (% PEs) for the PBBM, after incorporating in vitro data and the scaling factors, remained within acceptable regulatory limits.

Conclusions

The study demonstrated that a simple dynamic dissolution methodology can effectively predict in vivo bioequivalence and formulation performance. The application of the “dumping test” provided valuable insights into the dissolution characteristics of different formulations, highlighting its potential as a cost-effective and practical tool for biopredictive studies.

背景：近年来，人们在开发能够预测药物制剂体内行为的新的溶出度方法方面做出了重大努力。这对于建立有效的体内外相关性（IVIVCs）和生物预测模型至关重要。然而，许多这些方法涉及复杂、昂贵和复杂的设备，旨在复制人体生理学。本研究的目的是使用简化的动态溶出度方法预测体内生物等效性（BE），并建立一个基于生理学的生物制药模型（PBBM）。方法：采用缬沙坦（VALS， BCS IV类）和氢氯噻嗪（HCTZ， BCS III类）口服固定剂量联合用药进行研究。采用溶出度法对参比制剂（Co-Diovan®Forte）和两种仿制制剂进行评价。一种被称为“倾倒试验”的两阶段一室溶出技术被用于评估药物释放概况。将获得的体外溶出度数据纳入PBBM，并使用两个比例因子-一个是时间因子，另一个是吸收因子-以提高预测准确性。结果：“倾倒试验”成功地模拟了制剂的不同溶出行为，并解释了某些情况下生物等效性的失败。所建立的IVIVC具有良好的有效性和生物预测能力。在结合体外数据和比例因子后，PBBM的预测误差百分比（% PEs）仍在可接受的监管范围内。结论：简单的动态溶出度方法可有效预测制剂的体内生物等效性和制剂性能。“倾倒试验”的应用为了解不同制剂的溶出特性提供了有价值的见解，突出了其作为生物预测研究的成本效益和实用工具的潜力。

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引用次数: 0

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 : 2026-01-01 Epub 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 piperine/HPβCD-loaded PVA-coated iron oxide nanoparticles in in situ gel for enhanced retinal delivery and anti-VEGF activity 胡椒碱/ hpβ cd负载pva包被氧化铁纳米颗粒原位凝胶增强视网膜传递和抗vegf活性的开发。

IF 4.3 2区医学 Q1 PHARMACOLOGY & PHARMACY

European Journal of Pharmaceutics and Biopharmaceutics

Pub Date : 2026-01-01 Epub Date: 2025-11-08 DOI: 10.1016/j.ejpb.2025.114931

Phatsawee Jansook , Hay Man Saung Hnin Soe , Theingi Tun , Hay Marn Hnin , Supakarn Chamni , Rathapon Asasutjarit , Sarawut Lapmanee , Narumol Bhummaphan , Charoenchai Puttipanyalears , Sakkarin Bhubhanil , Anjaree Inchan , Natthawut Charoenphon , Yi Lu , Wei Wu

Piperine (PIP) is a potential therapeutic agent for retinal diseases; however, its poor aqueous solubility limits its ocular bioavailability. To overcome this limitation, a novel nanocarrier system was fabricated through the adsorption of PIP/hydroxypropyl-β-cyclodextrin (HPβCD) inclusion complexes onto the surface of polymer-stabilized iron oxide nanoparticles (IONs), which were then incorporated into an in situ gelling formulation. Three hydrophilic polymers, i.e., polyethylene glycol, poloxamer 407, and polyvinyl alcohol (PVA) were used as surface coatings. Among these, PIP/HPβCD/PVA-IONs exhibited the highest percent entrapment efficiency (77.38 ± 2.17 %) and superior mucoadhesive properties. Ocular safety was evaluated using the hen’s egg test on chorioallantoic membrane (HET-CAM), which indicated no irritation. To further enhance ocular retention and retinal delivery, the PIP/HPβCD/PVA-IONs were incorporated into an in situ gel. Upon contact with simulated tear fluid, the formulation underwent a sol-to-gel transition with excellent gelling capacity and improved ex vivo permeation across excised porcine cornea (0.85 ± 0.07 × 10^-6 cm⋅s⁻¹) and sclera (3.16 ± 0.29 × 10^-6 cm⋅s⁻¹). In vitro studies on ARPE-19 retinal cells demonstrated the formulation was non-toxic at concentrations up to 50 µg/mL (>70 % cell viability). Furthermore, in vitro and in vivo evaluations revealed that the formulation effectively suppressed vascular endothelial growth factor A at both the protein and mRNA levels. It also exhibited significant anti-inflammatory and anti-angiogenic effects. These findings suggest that the PIP/HPβCD-loaded IONs incorporated in in situ gel system offers a promising nanocarrier platform for targeted ocular drug delivery in the treatment of retinal diseases.

胡椒碱（PIP）是一种潜在的视网膜疾病治疗剂；然而，其水溶性差限制了其眼内生物利用度。为了克服这一限制，通过将PIP/羟丙基-β-环糊精（HPβCD）包合物吸附到聚合物稳定的氧化铁纳米颗粒（离子）表面，制备了一种新型纳米载体体系，然后将其掺入原位胶凝配方中。三种亲水性聚合物，即聚乙二醇，poloxam407和聚乙烯醇（PVA）被用作表面涂层。其中，PIP/ hp - β cd /PVA-IONs的包封率最高（77.38 ± 2.17 %），具有较好的粘接性能。采用绒毛膜-尿囊膜（HET-CAM）鸡蛋试验评价其眼部安全性，无刺激反应。为了进一步增强眼潴留和视网膜传递，将PIP/HPβCD/ pva -离子掺入原位凝胶中。与模拟眼泪液接触后，该配方发生了溶胶-凝胶转变，具有优异的凝胶能力，并改善了切除的猪角膜（0.85 ± 0.07 × 10-6 cm⋅s-1）和巩膜（3.16 ± 0.29 × 10-6 cm⋅s-1）的体外渗透。ARPE-19视网膜细胞的体外研究表明，该制剂在浓度高达50 µg/mL （bbb70 %细胞存活率）时无毒。此外，体外和体内评估显示，该配方在蛋白质和mRNA水平上都能有效抑制血管内皮生长因子A。它还具有显著的抗炎和抗血管生成作用。这些发现表明，将PIP/ hp β cd负载离子结合到原位凝胶系统中，为治疗视网膜疾病的靶向眼部药物递送提供了一个有前景的纳米载体平台。

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引用次数: 0

Review of design strategies for active targeted drug delivery systems for pancreatic cancer 胰腺癌活性靶向给药系统设计策略综述。

IF 4.3 2区医学 Q1 PHARMACOLOGY & PHARMACY

European Journal of Pharmaceutics and Biopharmaceutics

Pub Date : 2026-01-01 Epub Date: 2025-11-09 DOI: 10.1016/j.ejpb.2025.114915

Aysha Rahmatulla , Xiaoling Bi , Ping Wang , Xueni Wang , Shuangshuang Li , Xinran Zhang , Xiaofang Qiao , Yuzhou Chen

Pancreatic cancer (PC) is frequently referred to as the “king of cancers” due to its high mortality rate and poor prognosis. Chemotherapy drugs of a traditional nature are confronted with a multitude of challenges, including poor water solubility, low bioavailability, significant toxic side effects, and poor patient tolerance. This article provides a comprehensive review of the epidemiological and pathophysiological features of PC. The review also highlights the key antigens and receptors that are overexpressed in PC cells, including antigens such as TROP2, MSLN, MUC, and CA19-9. Furthermore, the article covers receptors like EGFR, TfR, integrins, GPCRs, IGF, GPC1, TF, and MET. The text introduces current pancreatic cancer treatment drugs, including gemcitabine, tegafur, and albumin-bound paclitaxel. The text also discusses targeted drug delivery carriers for PC, including liposomes, carbon nanotubes, exosome, polymer micelles, nanoparticles, nanocrystals, and hydrogel-encapsulated nanoparticles. The review offers a concise overview of the antibodies and ligands employed in active targeted drug delivery systems for PC, including hRS7, αTROP2, MF-T, TAB004, HzMUC1, as well as ligands such as EGF, GE11 peptide, Tf, tTR14, XQ-2d, cNGQ, α5β1-targeted peptide, IGF1, and SDC1. The therapeutic effects and prospects of combining active targeting strategies with photothermal therapy, immunotherapy, and gene editing technology are discussed in this paper.

胰腺癌因其高死亡率和预后差，常被称为“癌症之王”。传统性质的化疗药物面临着水溶性差、生物利用度低、毒副作用大、患者耐受性差等诸多挑战。本文就PC的流行病学和病理生理特点作一综述。本综述还强调了在PC细胞中过度表达的关键抗原和受体，包括TROP2、MSLN、MUC和CA19-9等抗原。此外，本文还涵盖了EGFR、TfR、整合素、gpcr、IGF、GPC1、TF和MET等受体。本文介绍了目前的胰腺癌治疗药物，包括吉西他滨，替加福和白蛋白结合紫杉醇。文中还讨论了针对PC的药物递送载体，包括脂质体，碳纳米管，外泌体，聚合物胶束，纳米颗粒，纳米晶体和水凝胶封装的纳米颗粒。本文简要介绍了用于PC活性靶向药物传递系统的抗体和配体，包括hRS7、αTROP2、MF-T、TAB004、HzMUC1，以及配体如EGF、GE11肽、Tf、tTR14、XQ-2d、cNGQ、α5β1靶向肽、IGF1和SDC1。本文就主动靶向策略与光热疗法、免疫疗法、基因编辑技术相结合的治疗效果及前景进行了综述。

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