European Journal of Pharmaceutics and Biopharmaceutics最新文献_第10页

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 : 2025-12-01 Epub 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

Towards the development of a standard toolbox for compatibility testing of pediatric drug products with common dosing vehicles − Fruit juice, apple sauce, yogurt, and pudding 开发儿童药品与常用给药工具（果汁、苹果酱、酸奶和布丁）相容性测试的标准工具箱。

IF 4.3 2区医学 Q1 PHARMACOLOGY & PHARMACY

European Journal of Pharmaceutics and Biopharmaceutics

Pub Date : 2025-12-01 Epub Date: 2025-09-15 DOI: 10.1016/j.ejpb.2025.114868

Carolin Eckert , Cordula Stillhart , Leonie Wagner , Emmanuel Scheubel , Isabelle Prevot , Marc Lindenberg , Sandra Klein

Co-administration of oral drug products with dosing vehicles is common practice in pediatric drug administration. The present work focused on the development of a set of standard vehicles that reflects the key characteristics of four different vehicle types commonly used in the administration of pediatric drug formulations. The aim was to rationalize and standardize the compatibility assessment of pediatric dosage forms with individual vehicle types and thereby contribute to a better risk assessment regarding this route of administration. In order to develop the standard vehicles, a comprehensive number of fruit juices, apple sauces, yogurts, and puddings were characterized with regard to their physicochemical properties. The characterization results served as target values for a set of standard vehicles which was successfully developed and followed a design of experiments approach. These standard vehicles represent the first and central components of a standardized vehicle toolbox designed for global use. Their use will enable pharmaceutical developers and regulatory authorities to gain insight into the compatibility of pediatric medicines with these dosing vehicles. Pending validation through comparative studies with the original vehicles, for which data are forthcoming, the toolbox is expected to serve as a valuable resource for assessing the safety and feasibility of combining pediatric formulations with liquid or semi-solid vehicles, thereby supporting more informed decision-making in drug development.

口服药物与给药载体共同给药是儿科给药的常见做法。目前的工作重点是一套标准车辆的发展，反映了四种不同的车辆类型通常用于儿科药物配方管理的关键特点。目的是使儿童剂型与单个载体类型的相容性评估合理化和标准化，从而有助于更好地评估这种给药途径的风险。为了制定标准车辆，对果汁、苹果酱、酸奶和布丁的理化性质进行了全面的表征。表征结果作为一组标准车辆的目标值，该标准车辆已成功开发并遵循实验方法设计。这些标准车辆代表了为全球使用而设计的标准化车辆工具箱的第一个和核心组件。它们的使用将使制药开发商和监管当局能够深入了解儿科药物与这些给药工具的兼容性。在通过与原始载体的比较研究验证之前，该工具箱有望成为评估儿科配方与液体或半固体载体结合的安全性和可行性的宝贵资源，从而支持药物开发中更明智的决策。

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引用次数: 0

About the impact of hydrophilic organic solvents on the emulsifying properties of self-emulsifying drug delivery systems (SEDDS) 研究了亲水有机溶剂对自乳化给药系统乳化性能的影响。

IF 4.3 2区医学 Q1 PHARMACOLOGY & PHARMACY

European Journal of Pharmaceutics and Biopharmaceutics

Pub Date : 2025-12-01 Epub Date: 2025-09-29 DOI: 10.1016/j.ejpb.2025.114877

Ahmad Saleh , Khush Bakhat Afzal , Florina Veider , Soheil Haddadzadegan , Andreas Bernkop-Schnürch

This study presents the first comprehensive evidence that hydrophilic organic solvents markedly accelerate SEDDS emulsification under biorelevant conditions, while maintaining both stability and safety. These findings establish their critical role as functional excipients in the development of advanced oral lipid-based drug delivery systems. Three different hydrophilic organic solvents benzyl alcohol, ethanol and propylene glycol were incorporated into self-emulsifying drug delivery systems (SEDDS). The emulsification time of SEDDS, with and without these solvents, was evaluated in various media, including demineralized water and HEPES buffer pH 5 and 7.5. Additionally, the stability of the formed oily droplets in the presence of bile salts was assessed based on their size distribution, polydispersity index (PDI), and zeta potential. Furthermore, membrane toxicity of the formulations was tested on human red blood cells (RBCs). Due to the incorporation of 30% benzyl alcohol, ethanol and propylene glycol, emulsification time was 12-fold, 8.2-fold and 5.6-fold accellerated, respectively. Furthermore, SEDDS containing the hydrophilic organic solvents benzyl alcohol and ethanol exhibited no significant change in size distribution, PDI and zeta potential when exposed to bile salts. SEDDS containing benzyl alcohol showed the lowest membrane damaging effect of all tested hydrophilic organic solvents. According to these results, the emulsifying properties of SEDDS can be significantly accellerated by the addition of hydrophilic organic solvents, with benzyl alcohol emerging as the most promising option.

本研究首次提供了全面的证据，证明亲水有机溶剂在生物相关条件下显著加速了SEDDS的乳化，同时保持了稳定性和安全性。这些发现确立了它们作为功能性赋形剂在开发先进的口服脂质给药系统中的关键作用。将三种不同的亲水性有机溶剂苯甲醇、乙醇和丙二醇加入到自乳化给药系统中。在各种介质中，包括脱盐水和pH为5和7.5的HEPES缓冲液，评估了有和没有这些溶剂的SEDDS的乳化时间。此外，根据它们的大小分布、多分散指数（PDI）和zeta电位，评估了在胆汁盐存在下形成的油滴的稳定性。此外，还测试了制剂对人体红细胞（rbc）的膜毒性。加入30%的苯甲醇、乙醇和丙二醇，乳化时间分别加快了12倍、8.2倍和5.6倍。此外，含有亲水性有机溶剂苯甲醇和乙醇的SEDDS在暴露于胆盐时，其尺寸分布、PDI和zeta电位没有显著变化。在所有亲水有机溶剂中，含苯甲醇的SEDDS对膜的破坏作用最低。综上所述，添加亲水有机溶剂可以显著加快SEDDS的乳化性能，其中苯甲醇是最有希望的选择。

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引用次数: 0

Degradable glycyrrhetinic acid functionalized mesoporous silica nanoparticles enhanced liver cancer therapy 可降解甘草次酸功能化介孔二氧化硅纳米颗粒增强肝癌治疗。

IF 4.3 2区医学 Q1 PHARMACOLOGY & PHARMACY

European Journal of Pharmaceutics and Biopharmaceutics

Pub Date : 2025-12-01 Epub Date: 2025-09-30 DOI: 10.1016/j.ejpb.2025.114880

Zhenhua Li , Junjie Zhang , Chuanyong Fan , Kaifang Wu , Jiaping Liu , Yaru Zhang , Zehao Dong , Fang Dong , Lu Xu

The study aimed to design a drug delivery system (DDS) with smart responsiveness in the tumor microenvironment (TME). Herein, manganese-doped mesoporous silica nanoparticles with glycyrrhetinic acid (GA) on their surface (MMSN-GA) were constructed to form a liver-targeted nanocarrier system, which achieved pH/GSH responsive drug release in TME and killed liver cancer cells through the combination of chemotherapy and chemodynamic therapy. The nanocarriers had the advantages of uniform particle size, considerable drug loading efficiency (26.26%), and superior pH/GSH dependency. MMSN-GA exhibited cytocompatibility with HepG-2 cells and high cellular uptake according to MTT and confocal laser scanning microscopy (CLSM) results. Moreover, MMSN-GA@DOX demonstrated excellent antitumor therapeutic effects, and the tumor inhibition rate was 92.32% in tumor-bearing mice. Overall, the MMSN-GA@DOX represents a promising approach for tumor-targeted therapy.

该研究旨在设计一种在肿瘤微环境（TME）中具有智能响应性的药物传递系统（DDS）。本文构建表面带有甘草酸（GA）的锰掺杂介孔二氧化硅纳米颗粒（MMSN-GA），形成肝脏靶向纳米载体体系，在TME中实现pH和GSH响应性药物释放，并通过化疗和化疗动力学联合治疗杀死肝癌细胞。该纳米载体具有粒径均匀、载药效率高（26.26%）、pH/GSH依赖性强等优点。根据MTT和共聚焦激光扫描显微镜（CLSM）结果，MMSN-GA表现出与HepG-2细胞的细胞相容性和高细胞摄取。此外，MMSN-GA@DOX具有良好的抗肿瘤治疗作用，对荷瘤小鼠的肿瘤抑制率为92.32%。总的来说，MMSN-GA@DOX代表了一种很有希望的肿瘤靶向治疗方法。

引用次数: 0

Poly(vinyl alcohol) cryogels: Effect size of polymer concentration, number of cycles and thawing rate on material properties and dermal drug delivery 聚乙烯醇低温冰箱：聚合物浓度、循环次数和解冻速率对材料性能和皮肤给药的影响大小。

IF 4.3 2区医学 Q1 PHARMACOLOGY & PHARMACY

European Journal of Pharmaceutics and Biopharmaceutics

Pub Date : 2025-12-01 Epub Date: 2025-09-28 DOI: 10.1016/j.ejpb.2025.114876

Y. Wiedemann , T. Schmitt , S. Kim , K. Dirnberger , S. Ludwigs , D.J. Lunter

Poly(vinyl alcohol) (PVA) can be physically cross-linked by repeated freeze–thaw (F-T) cycles, resulting in a cryogel. Despite the growing prevalence of the cryogelation process in the scientific literature, its multivariable nature, particularly the individual and synergistic impact of process variables on material properties, remains under-explored. The present work is the first systematic analysis quantifying the effect sizes associated with the influence of the key process parameters polymer concentration, number of cycles and thawing rates within F-T-cycles on the material properties of PVA cryogels as a drug delivery system for dermal applications. The variables analysed showed both positive and negative correlations with Young’s modulus, gel strength and calculated mesh sizes of the polymer network to varying degrees. Moreover, it uniquely demonstrates the synergistic combination effects between individual process parameters, revealing mutual influences, that had not been characterized systematically before. The excellent suitability as a dermal drug delivery system was also demonstrated by both comparative drug release and drug permeation through the skin using diclofenac sodium as a model drug. Overall, this study provides the first systematic understanding of the impact of cryogelation process parameters on material properties and introduces a new and simple approach to individual selection of specific cryogelation conditions.

聚乙烯醇（PVA）可以通过反复的冻融（F-T）循环进行物理交联，从而形成冷冻凝胶。尽管冷冻过程在科学文献中越来越普遍，但其多变量性质，特别是工艺变量对材料特性的单个和协同影响，仍未得到充分探索。本研究首次系统分析了关键工艺参数聚合物浓度、循环次数和f - t循环内的解冻速率对PVA冷冻箱材料性能的影响。PVA冷冻箱是一种用于皮肤的给药系统。分析的变量与杨氏模量、凝胶强度和计算出的聚合物网络的网状尺寸有不同程度的正相关和负相关。此外，它独特地展示了单个工艺参数之间的协同组合效应，揭示了相互影响，这是以前没有系统表征的。以双氯芬酸钠为模型药物，通过比较药物释放和药物通过皮肤的渗透也证明了双氯芬酸钠作为皮肤给药系统的优异适用性。总的来说，这项研究首次系统地了解了冷冻工艺参数对材料性能的影响，并引入了一种新的简单方法来单独选择特定的冷冻条件。

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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 : 2025-12-01 Epub 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

Polystyrene beads for efficient temperature control and drug nanoparticle production in wet stirred media milling 聚苯乙烯珠有效的温度控制和药物纳米颗粒生产在湿搅拌介质研磨。

IF 4.3 2区医学 Q1 PHARMACOLOGY & PHARMACY

European Journal of Pharmaceutics and Biopharmaceutics

Pub Date : 2025-12-01 Epub Date: 2025-09-30 DOI: 10.1016/j.ejpb.2025.114879

Hamidreza Heidari , Wren McAleer , Gulenay Guner , Donald J. Clancy , Ecevit Bilgili

This study explores the effects of stirrer speed, bead loading, and bead size on the evolution of mill outlet temperature during the wet stirred media milling (WSMM) of fenofibrate suspensions using crosslinked polystyrene (CPS) beads. Key parameters, including mill outlet temperature, particle size, suspension viscosity, and power consumption, were systematically measured. Power-law correlations were established to link the normalized temperature rise and power consumption with process parameters, revealing that stirrer speed exerts the greatest influence on both metrics, followed by bead loading and size. Notably, all milling runs, even under the highest power density conditions, were completed in a single cycle, eliminating the need for intermittent milling. The maximum temperature rise observed was 25 °C. Moreover, a microhydrodynamic (MHD) model was developed to investigate the influence of process parameters on MHD metrics, establishing correlations between median particle size, dimensionless temperature, and MHD parameters. The results demonstrated that an increased average frequency of particle compression is directly associated with higher temperature rise and finer particle sizes, underscoring the role of MHD parameters in governing thermal behavior and particle size reduction. Furthermore, comparison with yttrium-stabilized zirconia (YSZ) beads showed that CPS beads generated significantly lower heat while achieving comparable particle size reductions, making them particularly advantageous for milling thermally labile drugs. This study highlights the suitability of CPS beads for efficient and controlled WSMM, providing a promising alternative to YSZ beads for applications requiring stringent temperature control.

本研究探讨了使用交联聚苯乙烯（CPS）微球进行非诺贝特混悬液湿搅拌（WSMM）过程中，搅拌速度、微球载荷和微球大小对磨机出口温度变化的影响。系统地测量了磨机出口温度、粒度、悬浮液粘度和功耗等关键参数。建立了将归一化温升和功耗与工艺参数联系起来的幂律相关性，表明搅拌速度对这两个指标的影响最大，其次是头载荷和尺寸。值得注意的是，即使在最高功率密度条件下，所有磨铣都可以在一个周期内完成，从而消除了间歇性磨铣的需要。观测到的最高温升为25 °C。此外，建立了微流体动力学（MHD）模型来研究工艺参数对MHD指标的影响，建立了中位粒径、无因次温度和MHD参数之间的相关性。结果表明，颗粒压缩平均频率的增加与更高的温升和更细的颗粒尺寸直接相关，强调了MHD参数在控制热行为和颗粒尺寸减小方面的作用。此外，与钇稳定氧化锆（YSZ）珠粒的比较表明，CPS珠粒产生的热量明显更低，同时实现了类似的颗粒尺寸减小，这使得它们特别有利于研磨热不稳定的药物。该研究强调了CPS珠用于高效可控WSMM的适用性，为需要严格温度控制的应用提供了YSZ珠的有希望的替代品。

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引用次数: 0

Design of peptide functionalized nitrogen doped graphene quantum dots for theranostic application in breast cancer 肽功能化氮掺杂石墨烯量子点在乳腺癌治疗中的应用设计

IF 4.3 2区医学 Q1 PHARMACOLOGY & PHARMACY

European Journal of Pharmaceutics and Biopharmaceutics

Pub Date : 2025-11-01 Epub Date: 2025-08-26 DOI: 10.1016/j.ejpb.2025.114842

Vrushti Kansara, Mitali Patel

The nitrogen doped graphene quantum dots (N-GQDs) were functionalized for active targeting of epidermal growth factor receptor (EGFR) overexpressed breast cancer cells for the delivery of palbociclib (PLB). The N-GQDs were covalently conjugated with a dodecapeptide, GE11 (YHWYGYTPQNVI), a ligand with high affinity for EGFR and then loaded with PLB. The resulting PLB loaded N-GQDs (PLB-N-GQDs) and GE11-N-GQDs (GE11-PLB-N-GQDs) exhibited particle size of 85.25 ± 1.65 nm and 115.1 ± 2.47 nm, respectively. The surface functionalization of GE11 was confirmed by amide bond formation. The high-resolution transmission electron microscopy study revealed structural distortion in the GE11-PLB-N-GQDs due to functionalization and drug loading. The formulations were hemocompatible and hence were suitable for direct administration. The GE11-PLB-N-GQDs showed significantly higher release at pH 5.5 than pH 6.8 and pH 7.4. The confocal microscopy displayed the use of inherent fluorescence of the N-GQDs and GE11-N-GQDs across MCF-7 cells indicating their potential for bioimaging. The increased cellular uptake of the GE11-N-GQDs demonstrated effective EGFR targeting which increased cytotoxicity by the GE11-PLB-N-GQDs as compared to the PLB-N-GQDs. The GE11-PLB-N-GQDs induced G1 phase cell cycle arrest and apoptosis. This study demonstrates the potential of GE11-N-GQDs as a versatile theranostic nanocarrier for targeted delivery to breast cancer cells overexpressing EGFR.

氮掺杂石墨烯量子点（N-GQDs）被功能化，用于活性靶向表皮生长因子受体（EGFR）过表达的乳腺癌细胞，以递送帕博西尼（PLB）。N-GQDs与EGFR高亲和力配体十二肽GE11 （YHWYGYTPQNVI）共价偶联，然后装载PLB。结果表明，负载PLB的N-GQDs （PLB-N-GQDs）和GE11-N-GQDs （GE11-PLB-N-GQDs）的粒径分别为85.25±1.65 nm和115.1±2.47 nm。通过酰胺键的形成证实了GE11的表面功能化。高分辨率透射电镜研究显示，由于功能化和药物负载，GE11-PLB-N-GQDs存在结构畸变。该制剂具有血液相容性，适合直接给药。GE11-PLB-N-GQDs在pH 5.5下的释放量显著高于pH 6.8和pH 7.4。共聚焦显微镜显示了N-GQDs和GE11-N-GQDs在MCF-7细胞上的固有荧光，表明它们具有生物成像的潜力。与PLB-N-GQDs相比，GE11-PLB-N-GQDs的细胞摄取增加表明EGFR靶向性有效，从而增加了GE11-PLB-N-GQDs的细胞毒性。GE11-PLB-N-GQDs诱导G1期细胞周期阻滞和凋亡。这项研究证明了GE11-N-GQDs作为靶向递送到过表达EGFR的乳腺癌细胞的多功能治疗纳米载体的潜力。

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引用次数: 0

Effect of the combination of ion-pairs strategies and permeation enhancers on iguratimod transdermal patch against rheumatoid arthritis 离子对策略联合渗透促进剂对类风湿关节炎iguratimod透皮贴剂的作用。

IF 4.3 2区医学 Q1 PHARMACOLOGY & PHARMACY

European Journal of Pharmaceutics and Biopharmaceutics

Pub Date : 2025-11-01 Epub Date: 2025-09-05 DOI: 10.1016/j.ejpb.2025.114863

Yuyi Xu , Ting Fang , Sen Mu , Ji Li , Hongwei Li , Dongkai Wang

Iguratimod (IGU) is a novel anti-rheumatic drug that has anti-inflammatory effects, inhibits bone destruction, and promotes bone formation. However, the gastrointestinal side effects caused by oral tablets of IGU pose a challenge. This study aimed to develop an IGU transdermal patch for Rheumatoid Arthritis (RA) through ion-pair and chemical penetrant strategies to improve the therapeutic efficacy. The IGU patch was prepared using IGU-HERP (ion-pair), POCC (permeation promoter), DT 87-4098 (pressure-sensitive adhesive (PSA)), Backings 9720 (backing layer), with component ratios optimized through BBD experiments. The resulting formulations increase the IGU loading and skin penetration of the patch. Then the mechanism of permeation promotion of POCC was investigated in terms of the drug and skin. The molecular interactions between POCC and IGU ion-pairs were investigated by ex vitro artificial membranes, FT-IR, ¹³C NMR, and molecular simulation experiments. The interaction between POCC and skin stratum corneum was investigated using saturated drug solution permeation assay, exfoliation of stratum corneum assay, ATR-FTIR assay, SEM assay, and molecular simulation experiment. The results showed that hydrogen bonding between IGU-HEPR and POCC promoted drug release, while POCC would disrupt the dense structure of the stratum corneum and enhance drug penetration. When IGU-HEPR transdermal patches were applied to the rat model, IGU-HEPR transdermal patches exhibited good analgesic and anti-inflammatory effects. In conclusion, this study successfully developed an IGU patch for local administration against RA, providing a reference for improving the penetration of transdermal patches by using an ion-pair strategy.

Iguratimod （IGU）是一种新型抗风湿药物，具有抗炎作用，抑制骨破坏，促进骨形成。然而，口服IGU片剂引起的胃肠道副作用是一个挑战。本研究旨在通过离子对和化学渗透策略开发IGU类风湿性关节炎（RA）透皮贴剂，以提高其治疗效果。采用IGU- herp（离子对）、POCC（渗透促进剂）、DT 87-4098（压敏胶）、Backings 9720（衬底层）制备IGU贴片，并通过BBD实验优化组分配比。由此产生的配方增加了IGU负荷和贴片的皮肤穿透性。然后从药物和皮肤两方面探讨了POCC促进细胞渗透的机制。通过体外人工膜、FT-IR、13C NMR和分子模拟实验研究了POCC和IGU离子对之间的分子相互作用。采用饱和药物溶液渗透法、角质层脱落法、ATR-FTIR法、SEM法和分子模拟实验研究POCC与皮肤角质层的相互作用。结果表明，IGU-HEPR与POCC之间的氢键作用促进了药物的释放，而POCC会破坏角质层的致密结构，增强药物的渗透能力。小鼠模型经IGU-HEPR透皮贴敷后，IGU-HEPR透皮具有良好的镇痛、抗炎作用。综上所述，本研究成功研制出抗RA的IGU贴片，为利用离子对策略提高透皮贴片的透透性提供了参考。

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引用次数: 0

Thermosensitive chitosan-oxidized dextran-β-glycerophosphate sodium injectable hydrogel for enhanced solubility and prolonged release of ethinylestradiol: a novel long-acting contraceptive platform 热敏壳聚糖氧化葡聚糖-β-甘油磷酸钠注射水凝胶增强溶解度和延长释放乙炔雌二醇：一个新的长效避孕平台。

IF 4.3 2区医学 Q1 PHARMACOLOGY & PHARMACY

European Journal of Pharmaceutics and Biopharmaceutics

Pub Date : 2025-11-01 Epub Date: 2025-09-22 DOI: 10.1016/j.ejpb.2025.114872

Xuena Zhang , Fengqiang Zhang , Chongwei Yin , Juan Xu , Ting Wang

Ethinylestradiol (EE) is a clinically used estrogen with antifertility effects that is poorly water soluble, limiting bioavailability and preventing long-term release when administered orally. This study addresses these challenges through the development of a novel injectable thermosensitive hydrogel that both improves hydrophobic EE dispersion and enables sustained in vivo release, presenting significant potential for long-term contraception. Carboxymethyl-β-cyclodextrin (CM-β-CD) was synthesized to encapsulate EE, thereby enhancing its solubility and distribution in the hydrogel matrix. We found that hydrogels prepared by adding 0.5% (w/v) oxidized dextran (ODex) to the chitosan/sodium β-glycerophosphate (CS/ODex/β-GP) system exhibited mechanical strength favorable for cell growth compared to conventional CS/β-GP, resolved the problems of poor stability and mechanical strength of CS/β-GP hydrogels, and ensured effective retention and delivery in vivo. A 240h drug release study demonstrated the hydrogel’s ability to sustain release, highlighting its potential to prolong contraceptive efficacy. Biocompatibility testing showed cell viability in excess of 85%. FTIR and SEM characterization further confirmed the functional structure and morphology of the hydrogel. This thermosensitive injection system provides a promising platform for the long-term release of hydrophobic drugs such as EE, providing an innovative approach to extended contraceptive delivery.

炔雌醇（EE）是临床上使用的雌激素，具有抗生育作用，水溶性差，限制生物利用度，口服时不能长期释放。本研究通过开发一种新型可注射热敏水凝胶来解决这些挑战，这种水凝胶既能改善疏水EE的分散，又能在体内持续释放，具有长期避孕的巨大潜力。合成羧甲基-β-环糊精（CM-β-CD）包封EE，提高其在水凝胶基质中的溶解度和分布。结果表明，在壳聚糖/β-甘油磷酸钠（CS/ODex/β-GP）体系中添加0.5% （w/v）氧化右旋糖酐（ODex）制备的水凝胶与常规CS/β-GP相比，具有有利于细胞生长的机械强度，解决了CS/β-GP水凝胶稳定性差、机械强度差的问题，并保证了水凝胶在体内的有效保留和递送。一项240小时的药物释放研究表明，水凝胶具有持续释放的能力，突出了其延长避孕效果的潜力。生物相容性试验表明，细胞存活率在85%以上。FTIR和SEM表征进一步证实了水凝胶的功能结构和形态。这种热敏注射系统为疏水药物（如EE）的长期释放提供了一个有前景的平台，为延长避孕药的递送提供了一种创新的方法。

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引用次数: 0