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

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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引用次数: 0

Probing in vivo drug release of macrophage-targeting liposomes 巨噬细胞靶向脂质体的体内药物释放探测

IF 4.3 2区医学 Q1 PHARMACOLOGY & PHARMACY

European Journal of Pharmaceutics and Biopharmaceutics

Pub Date : 2026-01-01 Epub Date: 2025-11-25 DOI: 10.1016/j.ejpb.2025.114941

Hongling Xu , Yangxue Su , Hailong Ma , Xin Zeng , Manlin Wang , Weijie Chen , Xingyu Chen , Qing Zhou , Yang Li , Yaxin Zheng

Macrophages can internalize liposomes and disrupt them to facilitate drug release in the body. However, the effect of targeting liposomes to macrophages on in vivo drug release remains unclear. In this study, we compared the in vivo drug release from macrophage-targeting liposomes (modified with 1,2-distearoyl phosphatidylserine, PS) and PEGylated liposomes in 4 T1 breast tumor-bearing mice. The macrophage-targeting capability of PS-modified liposomes was confirmed by their significantly enhanced cellular uptake in macrophages compared to that of PEGylated liposomes. In vivo drug release studies showed that PS-modified liposomes exhibited higher drug release in various tissues than that of PEGylated liposomes, suggesting that macrophages facilitate the release of the drug from liposomes in the body. Despite a higher percentage of drug release in the tumor, the PS-modified liposomes did not improve antitumor activity compared to PEGylated liposomes due to their rapid clearance. These results suggest that targeting liposomes to macrophages can enhance in vivo drug release but fail to increase antitumor activity due to low tumor selectivity. Therefore, selectively targeting liposomes to tumor-associated macrophages is essential for boosting antitumor effects.

巨噬细胞可以内化脂质体并破坏它们以促进药物在体内的释放。然而，脂质体靶向巨噬细胞对体内药物释放的影响尚不清楚。在这项研究中，我们比较了巨噬细胞靶向脂质体（1,2-二硬脂酰磷脂酰丝氨酸，PS修饰）和聚乙二醇化脂质体在4只T1乳腺荷瘤小鼠体内的药物释放情况。与聚乙二醇化脂质体相比，ps修饰脂质体在巨噬细胞中的细胞摄取显著增强，证实了其巨噬细胞靶向能力。体内药物释放研究表明，ps修饰脂质体在各组织中的药物释放均高于聚乙二醇化脂质体，提示巨噬细胞促进了体内脂质体的药物释放。尽管肿瘤中药物释放的百分比更高，但由于ps修饰脂质体的快速清除，与聚乙二醇修饰脂质体相比，其抗肿瘤活性并没有提高。这些结果表明，将脂质体靶向巨噬细胞可以促进体内药物释放，但由于肿瘤选择性低，不能提高抗肿瘤活性。因此，选择性地将脂质体靶向肿瘤相关巨噬细胞对于增强抗肿瘤作用至关重要。

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引用次数: 0

Synergistic co-processing of heat-moisture treated resistant rice starch with HPMC and Eudragit® S100: A novel multifunctional excipient for direct compression and colon-targeted delivery HPMC和Eudragit®S100协同加工耐热湿处理大米淀粉：一种新型多功能赋形剂，用于直接压缩和结肠靶向递送。

IF 4.3 2区医学 Q1 PHARMACOLOGY & PHARMACY

European Journal of Pharmaceutics and Biopharmaceutics

Pub Date : 2026-01-01 Epub Date: 2025-11-04 DOI: 10.1016/j.ejpb.2025.114913

Karnkamol Trisopon , Phennapha Saokham , Nisit Kittipongpatana , Neungreuthai Chomchoei , Ornanong Suwannapakul Kittipongpatana

A novel multifunctional excipient was developed based on co-processed resistant rice starch (RRS) for direct compression (DC) tablet and targeted colonic drug delivery. While rice starch (RS) is biodegradable and exhibits good compressibility for DC, its poor flowability and low resistant starch content limit its applicability in both DC and controlled-release formulations. To address these limitations, RS was modified using heat-moisture treatment (HMT) with optimal process parameters (moisture content, temperature, and treatment time) were determined through a design of experiments (DoE) approach. The optimized HMT conditions successfully increased resistant starch content by approximately fourfold compared with native RS, and enhanced the plastic deformation properties of RRS, improving its compressibility. To achieve targeted colonic release, a pH-sensitive and enzyme-degradable polymer system was incorporated. The optimized RRS was co-processed with high-viscosity HPMC and Eudragit® S100 through wet granulation to obtain a co-processed excipient (CRRS). The resulting CRRS demonstrated enhanced flowability, packing efficiency, and plastic deformation characteristics, meeting all SeDeM expert system criteria for DC suitability. The corrective excipient proportion (CP, %) indicated a high dilution capacity, supporting drug loading of up to 55 %. Tablets containing 30 % w/w 5-aminosalicylic acid (5-ASA) as a model drug, prepared by DC using CRRS, exhibited acceptable uniformity of dosage units, friability, and drug content. In vitro dissolution studies revealed a controlled-release pattern, achieving approximately 80 % cumulative release within 12 h. The dense matrix formed by resistant starch and functional polymers effectively restricted water penetration and enzymatic access, promoting gradual and site-specific release under colonic conditions compared with tablets lacking RRS. Release kinetics followed the Higuchi model, with n values suggesting an anomalous transport mechanism involving both diffusion and erosion. Overall, CRRS represents a promising multifunctional excipient combining excellent DC performance with controlled, site-specific colonic drug delivery potential, supporting the development of advanced oral dosage forms.

以耐药大米淀粉（RRS）为原料，研制了一种用于直接压片和结肠靶向给药的新型多功能赋形剂。虽然大米淀粉具有生物可降解性和良好的DC压缩性，但其流动性差和抗性淀粉含量低限制了其在DC和控释制剂中的适用性。为了解决这些局限性，采用热湿处理（HMT）对RS进行了修改，并通过实验设计（DoE）方法确定了最佳工艺参数（水分含量、温度和处理时间）。优化后的HMT条件成功地使抗性淀粉含量比天然RS提高了约4倍，并增强了RRS的塑性变形性能，提高了其压缩性能。为了实现目标结肠释放，加入了ph敏感和酶降解的聚合物系统。将优化后的RRS与高粘度HPMC和Eudragit®S100进行湿造粒共加工，得到共加工辅料（CRRS）。结果表明，CRRS具有更好的流动性、填充效率和塑性变形特性，符合SeDeM专家系统对直流适用性的所有标准。校正辅料比例（CP, %）显示高稀释能力，支持药物负荷高达55 %。以30 % w/w 5-氨基水杨酸（5-ASA）为模型药物，采用CRRS直流法制备的片剂，其剂量单位、脆性和药物含量均可接受。体外溶出度研究显示出控释模式，在12 h内达到约80 %的累积释放。与缺乏RRS的片剂相比，由抗性淀粉和功能聚合物形成的致密基质有效地限制了水的渗透和酶的进入，促进了结肠条件下逐渐和特定部位的释放。释放动力学遵循Higuchi模型，其中n值表明涉及扩散和侵蚀的异常运输机制。总的来说，CRRS是一种很有前途的多功能赋形剂，结合了优良的DC性能和可控的、特定部位的结肠给药潜力，支持高级口服剂型的开发。

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引用次数: 0

Analysis of discrepancy in SNEDDS performance for a “brick dust” mebendazole between in-vitro and in-vivo estimation “砖粉”甲苯达唑体内、体外SNEDDS性能差异分析。

IF 4.3 2区医学 Q1 PHARMACOLOGY & PHARMACY

European Journal of Pharmaceutics and Biopharmaceutics

Pub Date : 2026-01-01 Epub Date: 2025-11-01 DOI: 10.1016/j.ejpb.2025.114911

Seito Maehara , Saki Nishiyama , Masato Maruyama , Kazutaka Higaki

Oral absorption of mebendazole (MBZ), a brick dust, was successfully improved 10 times by dosing 2% HPMCP-50 SNEDDS of MBZ co-amorphized with (+)-10-camphorsulufonic acid (CSA) (MBZ-CSA), compared with crystal powders in our previous study. However, an in-vitro non-sink dissolution study with pH3.9 acetate buffer or FaSSIF (conventional method) revealed that 2% HPMCP-50 SNEDDS of MBZ-CSA improved the dissolution of MBZ over 440 times compared to the crystal. In the current study, we assessed the reason for the large discrepancy in SNEDDS performance between in-vitro and in-vivo estimations using several novel in-vitro methods. The Sequential Gastro-Intestinal Exposure (SGIE) method, reflecting the transit from the stomach to the small intestine (GI-transit), revealed MBZ precipitation higher than that in the conventional method using FaSSIF. The Egg phosphatidylcholine-Monolayer-CHCl₃ Partition (EMCP) method, reflecting the absorption process, also indicated MBZ precipitation at early time periods greater than the conventional method. The SGIE-EMCP method, reflecting both GI-transit and subsequent absorption processes, indicated the highest precipitation of MBZ and MBZ transfer to the CHCl₃ phase less than the EMCP method. The SGIE-EMCP method also indicated that 2% HPMCP-50 SNEDDS transferred MBZ to the CHCl₃ phase significantly larger than SNEDDS without the polymer, which coincided with the in-vivo tendency.

用2 % HPMCP-50 SNEDDS与(+)-10-樟脑磺酸（CSA）（MBZ-CSA）共晶化，可将砖粉苯并达唑（MBZ）的口服吸收率提高10倍。然而，用pH3.9醋酸缓冲液或FaSSIF（常规方法）进行的体外非沉淀溶出研究表明，与晶体相比，2 % HPMCP-50 SNEDDS使MBZ- csa的溶出率提高了440倍以上。在目前的研究中，我们使用几种新颖的体外方法评估了体内和体外估计SNEDDS性能差异较大的原因。顺序胃肠道暴露（SGIE）方法，反映了从胃到小肠的传输（GI-transit），显示MBZ沉淀高于使用FaSSIF的常规方法。反映吸收过程的鸡蛋磷脂酰胆碱-单层- chcl3分割法（EMCP）也表明MBZ在早期的沉淀量大于常规方法。SGIE-EMCP方法反映了GI-transit和随后的吸收过程，表明MBZ的最大沉淀和MBZ向CHCl3相的转移少于EMCP方法。sgi - emcp方法还表明，2 % HPMCP-50的SNEDDS将MBZ转移到CHCl3相的量明显大于未添加聚合物的SNEDDS，这与体内趋势一致。

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引用次数: 0

Impact of terminal groups on PLGA degradation rate and their role in sustained release of cyproterone acetate 末端基团对PLGA降解速率的影响及其在醋酸环丙孕酮缓释中的作用。

IF 4.3 2区医学 Q1 PHARMACOLOGY & PHARMACY

European Journal of Pharmaceutics and Biopharmaceutics

Pub Date : 2026-01-01 Epub Date: 2025-11-12 DOI: 10.1016/j.ejpb.2025.114914

Qien Zhao , Junhui Yang , Jialin Liu , Shengyu Zhang , Wei Zhao , Wenting Jiang , Yang Zhou , Lei Jiang , Jiantao Zhang

Poly(lactic-co-glycolic acid) (PLGA) is the most commonly used commercially available polymeric pharmaceutical excipient for developing injectable long-acting release products. Its degradation rate is influenced by factors, such as molecular weight, the lactic/glycolic ratio (L/G ratio), and the nature of terminal groups. These variables impose challenges in achieving a precisely controlled release of loaded active compounds from finished PLGA-based formulations. This study investigated the impact of varying PLGA terminal groups on drug loading, encapsulation efficiencies, and drug release profiles in PLGA microspheres. We synthesized PLGA with four distinct terminal groups: carboxyl, n-hexyl, dodecyl, and hexadecyl, while keeping molecular weights and L/G ratios consistent to isolate the effects of the terminal groups on PLGA properties. Also, we examined how terminal groups influence the degradation behavior of PLGA microspheres and found that longer carbon chain lengths in the terminal groups resulted in a slower degradation rate. We have developed a novel method for analyzing terminal groups, enabling us to verify our synthesized products and to compare them against commercially available products. This method enhances the accuracy of our analyses and ensures the integrity of our product verification process. Additionally, we explored the underlying mechanism by which terminal groups affect the PLGA degradation. We then prepared four PLGA microspheres loaded with cyproterone acetate (CYA) through emulsification. The resulting microspheres exhibited consistent morphology, and a volume mean diameter of 9 to 11 µm,a drug loading rate of about 10% and an encapsulation efficiency of approximately 97%. The results of in vitro release experiments showed that CYA release from all microspheres could be sustained for up to two months with a recovery rate reaching 100%. Meanwhile, we investigated the mechanism of loaded drug release from PLGA microspheres with different terminal groups and elucidated how the degradation of PLGA influences the release profile of loaded drugs. The insights gained from this study will enhance the understanding of PLGA degradation and the mechanisms underlying the release of loaded actives from PLGA microspheres. Furthermore, the modification of terminal groups has the potential to support the development of advanced pharmaceutical excipients.

聚乳酸-羟基乙酸（PLGA）是一种最常用的商用高分子药物赋形剂，用于开发可注射的长效释放产品。其降解速率受分子量、乳酸/乙醇比（L/G ratio）、末端基团性质等因素的影响。这些变量对从成品的基于plga的配方中实现负载活性化合物的精确控制释放提出了挑战。本研究考察了不同PLGA末端基团对PLGA微球中载药、包封效率和药物释放谱的影响。我们合成了具有羧基、正己基、十二烷基和十六烷基四个不同末端基的PLGA，同时保持分子量和L/G比一致，以分离末端基对PLGA性能的影响。此外，我们研究了末端基团如何影响PLGA微球的降解行为，发现末端基团的碳链长度越长，降解速度越慢。我们开发了一种分析终端基团的新方法，使我们能够验证我们的合成产品，并将它们与市售产品进行比较。这种方法提高了我们分析的准确性，并确保了我们产品验证过程的完整性。此外，我们还探讨了末端基团影响PLGA降解的潜在机制。然后通过乳化法制备了4个负载醋酸环丙孕酮（CYA）的PLGA微球。所得微球形貌一致，体积平均直径为9 ~ 11 µm，载药率约为10 %，包封效率约为97 %。体外释放实验结果表明，所有微球的CYA释放持续时间可达2个月，回收率达100% %。同时，我们研究了不同末端基团的PLGA微球的载药释放机制，并阐明了PLGA降解对载药释放的影响。从这项研究中获得的见解将加强对PLGA降解和PLGA微球释放负载活性物质的机制的理解。此外，末端基团的修饰具有支持先进药用辅料开发的潜力。

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引用次数: 0

Pharmacomagnetography of floating gastroretentive systems in vivo in different prandial states evaluated by AC biosusceptometry 体内漂浮胃保留系统在不同进食状态下的药磁图。

IF 4.3 2区医学 Q1 PHARMACOLOGY & PHARMACY

European Journal of Pharmaceutics and Biopharmaceutics

Pub Date : 2026-01-01 Epub Date: 2025-11-07 DOI: 10.1016/j.ejpb.2025.114907

Gustavo Serafim Rodrigues , Laís Pereira Buranello , João Miguel Barboza , Michael José Abílio Almeida , Erick Guilherme Stoppa , Priscileila Colerato Ferrari , Guilherme Augusto Soares , José Ricardo de Arruda Miranda

<div><div>In recent decades, the development of effective therapies with minimal adverse effects has become a major challenge in the pharmaceutical field. Despite its popularity, oral administration faces limitations related to the physiological variability of the gastrointestinal tract (GIT), such as gastric emptying time, absorption window, and site of drug release. In this context, modified-release systems—especially gastroretentive drug delivery systems (GRDDS)—have gained prominence. GRDDS aim to prolong gastric retention time (GRT), facilitating controlled and localized drug release, particularly beneficial for drugs with limited absorption windows or instability in alkaline pH. This study evaluated the in vivo performance of a magnetic floating drug delivery system (MFDDS) containing metronidazole using pharmacomagnetography based on alternating current biosusceptometry (ACB) in healthy volunteers (n = 12, aged 19–21 years) under fasted and fed conditions. Results demonstrated that the prandial state significantly influenced MFDDS behavior, with food intake prolonging both the floating lag time (FLT) (105–120 min fed vs. 45–60 min fasted) and gastric retention time (GRT) (<span><math><mrow><mn>165.0</mn><mo>±</mo><mn>32.2</mn></mrow></math></span> min fed vs. <span><math><mrow><mn>118.3</mn><mo>±</mo><mn>35.3</mn></mrow></math></span> min fasted, p < 0.0001). The orocecal transit time (OCTT) was similar between groups (<span><math><mrow><mn>271.7</mn><mo>±</mo><mn>32.0</mn></mrow></math></span> min fed vs. <span><math><mrow><mn>254.2</mn><mo>±</mo><mn>44.9</mn></mrow></math></span> min fasted, p > 0.05), while small intestine transit time (SITT) was shorter in the fed state (<span><math><mrow><mn>111.7</mn><mo>±</mo><mn>22.3</mn></mrow></math></span> min) compared to the fasted state (<span><math><mrow><mn>140.0</mn><mo>±</mo><mn>47.7</mn></mrow></math></span> min), though not statistically significant. Pharmacokinetic parameters showed significant differences, with the fed state resulting in delayed time to maximum concentration (<span><math><mrow><mi>Tmax</mi></mrow></math></span>) (<span><math><mrow><mn>252.0</mn><mo>±</mo><mn>52.9</mn></mrow></math></span> min fed vs. <span><math><mrow><mn>174.0</mn><mo>±</mo><mn>60.0</mn></mrow></math></span> min fasted, p < 0.05) but substantially higher maximum plasma concentrations (Cmax) (<span><math><mrow><mn>11.0</mn><mo>±</mo><mn>5.7</mn></mrow></math></span> µg/mL fed vs. <span><math><mrow><mn>4.7</mn><mo>±</mo><mn>2.2</mn></mrow></math></span> µg/mL fasted, p < 0.05) and area under the curve (AUC360) (<span><math><mrow><mn>2606.1</mn><mo>±</mo><mn>1825.5</mn></mrow></math></span> µg·h/mL fed vs. <span><math><mrow><mn>969.3</mn><mo>±</mo><mn>638.3</mn></mrow></math></span> µg·h/mL fasted, p < 0.05). The time lag before detectable plasma concentration (<span><math><mrow><mi>Tlag</mi></mrow></math></span>) was similar between groups (<span><math><mrow><mn>67.5</mn><mo>±</mo><mn>21

近几十年来，开发副作用最小的有效疗法已成为制药领域的主要挑战。尽管口服给药很受欢迎，但由于胃肠道（GIT）的生理变异性，如胃排空时间、吸收窗口和药物释放部位等，口服给药存在局限性。在这种背景下，修饰释放系统，特别是胃保留性药物传递系统（GRDDS）已经得到了重视。GRDDS旨在延长胃保留时间（GRT），促进药物的控制和局部释放，特别是对吸收窗口有限或碱性ph不稳定的药物有益。本研究利用基于交流电生物敏感性（ACB）的药物磁成像技术，在健康志愿者（n = 12，年龄19-21 岁）的禁食和进食条件下，评估了含有甲硝唑的磁漂浮给药系统（MFDDS）的体内性能。结果表明，进食状态显著影响MFDDS行为，食物摄入延长了漂浮滞后时间（FLT）（105-120 min进食vs 45-60 min禁食）和胃保留时间（GRT）（165.0±32.2 min进食vs 118.3±35.3 min禁食，p  0.05），而小肠转运时间（SITT）在进食状态下（111.7±22.3 min）比在禁食状态下（140.0±47.7 min）更短，但无统计学意义。药代动力学参数差异有统计学意义（p <  0.05），摄食状态导致达到最大浓度的时间延迟（Tmax）（摄食252.0±52.9 min vs禁食174.0±60.0 min）。在喂食状态下，胃内容物的粘度增加，通过在片剂周围形成疏水屏障，限制胃液扩散到聚合物基质中，延迟了片剂的初始浮选。进食状态下胃潴留的延长导致甲硝唑吸收更完全和持续，证实了胃潴留系统在优化药物生物利用度方面的有效性，特别是在餐后给药时。

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引用次数: 0

Naproxen printlets for extemporaneous dispersion: Designing new medicines for drug delivery through the enteral route 临时分散的萘普生小片：设计通过肠内途径给药的新药。

IF 4.3 2区医学 Q1 PHARMACOLOGY & PHARMACY

European Journal of Pharmaceutics and Biopharmaceutics

Pub Date : 2026-01-01 Epub Date: 2025-11-23 DOI: 10.1016/j.ejpb.2025.114939

Nadine Lysyk Funk , Flávia Carvalho Tavaniello , Edilson Valmir Benvenutti , Cesar Liberato Petzhold , Karina Paese , Monique Deon , Ruy Carlos Beck

Off-label use of medicines administered via enteral feeding tubes (EFT) can lead to dose inaccuracies, adverse effects and tube obstruction, compromising therapeutic outcomes. Thus, new manufacturing processes are required to design medicines specifically for EFT administration. In this study, a 3D printing semi-solid extrusion (SSE) technique was employed to produce circular-shaped naproxen printlets (P-NPX) (18 × 18 × 2.6 mm, 30 % infill) for aqueous dispersion prior to EFT administration. Mesoporous silica nanoparticles (MSN) were used as NPX nanocarriers for development of printlets (P-NPX-MSN). Results show that MSN drug encapsulation enabled production of printlets with reproducible NPX content, without organic solvents; while providing better shape retention. Aqueous dispersion times were 806 ± 26 s for P-NPX and 813 ± 20 s for P-NPX-MSN. For both formulations, resulting dispersions were slightly acidic (pH ∼ 5), with viscosity of 1.3 cP and particle size distribution that ensured NPX administration without tube obstruction. Drug recovery was ∼ 100 % for both formulations after tube passage. Re-dispersed printlets had reduced vascular event compared to positive controls in Hen’s Egg Test − Chorioallantoic Membrane (HET-CAM) assay (in vitro alternative model) and were classified as slight irritants. This study provides an innovative route for drugs presenting gastric irritation, advancing SSE 3D printing for personalised EFT medicines.

经肠内喂养管（EFT）给药的超说明书使用可导致剂量不准确、不良反应和管阻塞，影响治疗结果。因此，需要新的制造工艺来设计专门用于EFT管理的药物。在这项研究中，采用3D打印半固体挤压（SSE）技术，在EFT给药之前，生产出圆形的萘普生小块（P-NPX）（18 × 18 × 2.6 mm， 30 %填充）用于水分散。以介孔二氧化硅纳米颗粒（MSN）为NPX纳米载体，制备了P-NPX-MSN微球。结果表明，单分散微球药物包封可以在不使用有机溶剂的情况下制备具有可重复性的NPX含量的小片；同时提供更好的形状保持。P-NPX水溶液分散时间为806 ± 26 s， P-NPX- msn水溶液分散时间为813 ± 20 s。对于这两种配方，得到的分散体都是微酸性的（pH ~ 5），粘度为1.3 cP，粒径分布确保NPX给药不会堵塞管道。两种制剂通过试管后的药物回收率均为 ~ 100% %。在鸡蛋试验-绒毛膜-尿囊膜（et - cam）试验（体外替代模型）中，与阳性对照相比，再分散的小细胞血管事件减少，并被归类为轻微刺激物。这项研究为胃刺激药物提供了一条创新途径，推动了SSE 3D打印个性化EFT药物的发展。

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引用次数: 0

Corrigendum to “Dissolving microneedle-mediated dermal delivery of itraconazole nanocrystals for improved treatment of cutaneous candidiasis”. [Eur. J. Pharm. Biopharm. 154 (2020) 50–61] “溶解微针介导的伊曲康唑纳米晶体皮肤递送用于改善皮肤念珠菌病的治疗”的更正。(欧元。j .制药。生物医学工程学报，2014(5):559 - 561。

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.2025.114929

Andi Dian Permana , Alejandro J. Paredes , Fabiana Volpe-Zanutto , Qonita Kurnia Anjani , Emilia Utomo , Ryan F. Donnelly

引用次数: 0

A novel histidine-acetate buffer for freeze-dried monoclonal antibody formulations 一种用于冻干单克隆抗体制剂的新型组氨酸-醋酸酯缓冲液

IF 4.3 2区医学 Q1 PHARMACOLOGY & PHARMACY

European Journal of Pharmaceutics and Biopharmaceutics

Pub Date : 2026-01-01 Epub Date: 2025-11-25 DOI: 10.1016/j.ejpb.2025.114940

Jia-Yi Lv , Han Gao , Huan-Fang Xie , Meng-Jia Jin , Bin Di , Jin Xu , Wei-Jie Fang

Histidine (His)-hydrochloride (HCl) is widely used in freeze-dried monoclonal antibody (mAb) formulations, but alternative buffers are required when chloride ions are undesirable. This study evaluates His-acetate (Ac) as a substitute and its impact on the stability of two model mAbs with distinct physicochemical properties— infliximab (mAb-1) and a humanized anti-ricin mAb (mAb-2). pH shifts during freeze-drying were compared among His-Ac, His-HCl, and sodium Ac buffers, confirming strong buffering capacity of His-Ac within pH 5.5–6.5. Conformational and colloidal stability assessments revealed that both mAbs displayed higher melting temperatures or favorable diffusion interaction parameters in His-Ac formulations. Moreover, mAb-2 exhibited a higher collapse temperature in His-Ac compared to His-HCl, indicating improved structural integrity or drying efficiency during primary drying. No significant differences were observed in aggregation onset temperature and glass transition temperature. Aggregation and chemical stability under stress conditions were evaluated by micro-flow imaging, size exclusion chromatography, and ion exchange chromatography. No notable changes in subvisible particle counts or monomer content occurred after freeze-drying. Overall, His-Ac demonstrated stability comparable to or better than His-HCl, supporting its use in freeze-dried mAb formulations.

组氨酸(His)-盐酸（HCl）广泛用于冻干单克隆抗体（mAb）制剂，但当不需要氯离子时，需要替代缓冲液。本研究评估了His-acetate （Ac）作为替代品及其对两种具有不同物理化学性质的模型单抗-英夫利昔单抗（mAb-1）和人源抗蓖麻毒素单抗（mAb-2）稳定性的影响。比较了His-Ac、His-HCl和Ac钠缓冲液在冷冻干燥过程中的pH变化，证实了His-Ac缓冲液在pH值5.5-6.5之间具有较强的缓冲能力。构象和胶体稳定性评估表明，这两种单抗在His-Ac配方中具有更高的熔化温度或有利的扩散相互作用参数。此外，与His-HCl相比，mAb-2在His-Ac中表现出更高的坍塌温度，表明初次干燥时结构完整性或干燥效率得到改善。聚合起始温度和玻璃化转变温度无显著差异。通过微流成像、尺寸排除层析和离子交换层析来评价应力条件下的聚集性和化学稳定性。冷冻干燥后，不可见颗粒计数或单体含量无明显变化。总体而言，His-Ac表现出与His-HCl相当或更好的稳定性，支持其在冻干单抗制剂中的应用。

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引用次数: 0