International Journal of Pharmaceutics: X最新文献_第10页

Biomimetic nanotherapy for P. gingivalis-infected oral squamous cell carcinoma: Photothermal therapy and immunoactivation via precise intracellular bacterial elimination 仿生纳米疗法治疗牙龈卟啉卟啉感染的口腔鳞状细胞癌：光热疗法和通过精确的细胞内细菌消除的免疫激活

IF 6.4 2区医学 Q1 PHARMACOLOGY & PHARMACY

International Journal of Pharmaceutics: X

Pub Date : 2025-12-01 Epub Date: 2025-11-12 DOI: 10.1016/j.ijpx.2025.100438

Zihan Dai , Qiaoxin Li , Longxuan Guo , Kaijing Zhong , Jing Cheng , Xiuhong Weng , Bo Cheng

Porphyromonas gingivalis (P. gingivalis) infection in oral squamous cell carcinoma (OSCC) undermines patient responses to standard therapies by driving chemoresistance, tumor progression, and immune suppression. Mounting research evidence—including our staining of clinical OSCC biopsies—confirms intratumoral P. gingivalis colonization and CXCL2 overexpression as risk factors for poor prognosis. Therefore, precisely eliminating tumor-promoting microorganisms and alleviating immune suppression are crucial for improving the treatment efficacy. Inspired by validated observations, we have developed a unique clinically oriented nanoparticle platform (MC-MM@MPDA) that integrated precise intracellular antibiotic delivery, photothermal tumor ablation, photothermal bactericidal and immune activation. Despite growing interest in OSCC photothermal ablation, this platform is the first to utilize the dual anti-tumor and antibacterial functions of photothermal therapy aiming to achieve targeted therapy tailored to P. gingivalis-infected OSCC. Minocycline (MC) was loaded into mesoporous polydopamine (MPDA) nanoparticles and encapsulated with macrophage membranes, enabling selective homing to infected tumor sites and efficient uptake by cancer cells. Subsequently, the nanoplatform utilized photothermal effects to ablate tumor tissue, eliminate intracellular bacteria and induce immunogenic cell death (ICD). pH-triggered antibiotic release eradicated residual bacteria and unleashed bacterial tumor associated antigens. Alongside damage-associated molecular patterns (DAMPs) generated by ICD, these signals reprogrammed the immunosuppressive microenvironment and established a synergistic antitumor network. In P. gingivalis infected OSCC xenograft models, this platform dramatically suppressed tumor growth, cleared pathogen burden, and overcame bacteria-mediated therapy resistance. By leveraging membrane-mimetic targeting, and synergistic photothermal-immunotherapy, MC-MM@MPDA offered a scalable, biocompatible, and readily translatable strategy to address pathogen-driven barriers in OSCC therapy.

口腔鳞状细胞癌（OSCC）中的牙龈卟啉单胞菌（P. gingivalis）感染通过驱动化疗耐药、肿瘤进展和免疫抑制来破坏患者对标准治疗的反应。越来越多的研究证据——包括我们的临床OSCC活检染色——证实了瘤内牙龈假单胞菌定植和CXCL2过表达是预后不良的危险因素。因此，准确清除促瘤微生物，减轻免疫抑制是提高治疗效果的关键。受验证观察的启发，我们开发了一种独特的临床导向纳米颗粒平台（MC-MM@MPDA），该平台集成了精确的细胞内抗生素递送，光热肿瘤消融，光热杀菌和免疫激活。尽管人们对OSCC光热消融越来越感兴趣，但该平台是第一个利用光热治疗的双重抗肿瘤和抗菌功能，旨在实现针对牙龈假单胞菌感染的OSCC的靶向治疗。米诺环素（MC）被装载到介孔聚多巴胺（MPDA）纳米颗粒中，并被巨噬细胞膜包裹，使其能够选择性地归巢到感染的肿瘤部位，并被癌细胞有效吸收。随后，纳米平台利用光热效应消融肿瘤组织，消除细胞内细菌并诱导免疫原性细胞死亡（ICD）。ph触发的抗生素释放可根除残留细菌并释放细菌肿瘤相关抗原。与ICD产生的损伤相关分子模式（DAMPs）一起，这些信号重新编程了免疫抑制微环境，并建立了协同抗肿瘤网络。在牙龈假单胞菌感染的OSCC异种移植模型中，该平台显著抑制肿瘤生长，清除病原体负担，克服细菌介导的治疗耐药性。通过利用膜模拟靶向和协同光热免疫疗法，MC-MM@MPDA提供了一种可扩展、生物相容性和易于翻译的策略，以解决OSCC治疗中病原体驱动的障碍。

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引用次数: 0

CD276-directed supramolecular nanoplatform with pH-triggered gemcitabine release for potent tumor stromal and vascular suppression cd276导向的超分子纳米平台，ph触发吉西他滨释放，有效抑制肿瘤基质和血管

IF 6.4 2区医学 Q1 PHARMACOLOGY & PHARMACY

International Journal of Pharmaceutics: X

Pub Date : 2025-12-01 Epub Date: 2025-11-19 DOI: 10.1016/j.ijpx.2025.100452

Jiayi Li , Hao Liu , Zhijun Li , Zhihuan Zheng , Lanzhu Luo , Liqing Lin , Jizhen Lin , Gang Liu , Xinhua Lin , Bing Chen

Gemcitabine (Gem) remains a cornerstone chemotherapy for pancreatic ductal adenocarcinoma, but its clinical efficacy is limited by poor pharmacokinetics, dense fibrotic stroma, and hypovascularization. While pH-responsive liposomes can enhance circulation and targeted drug release, their clinical application is hindered by low drug loading capacity and premature leakage of hydrophilic drugs. To address these challenges, we exploited the high and specific expression of CD276 on pancreatic cancer cells, tumor vasculature, and fibroblasts. We engineered a high-specificity and high-affinity anti-CD276 scFv, and developed a novel nanoplatform (Gem@CPL) that integrates pH-responsive and supramolecular assembly strategies with Gem, achieving 4-fold higher drug loading, improved stability, and tumor-specific release. Cellular and animal studies confirmed that Gem@CPL facilitates tumor-specific accumulation and CD276-mediated internalization, resulting in improved intracellular delivery and therapeutic efficacy. Pharmacokinetic analysis revealed a 2.26-fold prolongation of half-life (t₁/₂) and a significant reduction in volume of distribution (Vd) to 0.11-fold compared to free Gem, indicating superior systemic exposure and minimized off-target distribution. Gem@CPL increased anti-tumor activity by 1.77-fold, demonstrating its enhanced efficacy via sustained circulation and targeted delivery. By specifically targeting CD276, this platform minimizes systemic toxicity and potentially improving patient tolerability, offering promising prospects for clinical translation and better outcomes in pancreatic cancer treatment.

吉西他滨（Gem）仍然是胰腺导管腺癌的基础化疗，但其临床疗效受到药代动力学差、纤维化间质致密和血管不足的限制。虽然ph响应性脂质体可以促进循环和靶向药物释放，但由于载药能力低和亲水药物过早渗漏，阻碍了其临床应用。为了解决这些挑战，我们利用了CD276在胰腺癌细胞、肿瘤血管和成纤维细胞中的高特异性表达。我们设计了一种高特异性和高亲和力的抗cd276 scFv，并开发了一种新的纳米平台（Gem@CPL），该平台将ph响应和超分子组装策略与Gem结合在一起，实现了4倍高的药物载量，提高了稳定性和肿瘤特异性释放。细胞和动物研究证实Gem@CPL促进肿瘤特异性积累和cd276介导的内化，从而改善细胞内递送和治疗效果。药代动力学分析显示，与游离Gem相比，半衰期（t₁/ 2）延长2.26倍，分布体积（Vd）显着减少至0.11倍，表明更好的全身暴露和最小的脱靶分布。Gem@CPL抗肿瘤活性增加了1.77倍，表明其通过持续循环和靶向给药增强了疗效。通过特异性靶向CD276，该平台最大限度地降低了全身毒性，并有可能提高患者的耐受性，为胰腺癌治疗提供了良好的临床转化前景和更好的结果。

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引用次数: 0

Plant-derived extracellular vesicles as a natural drug delivery platform for glioblastoma therapy: A dual role in preserving endothelial integrity while modulating the tumor microenvironment 植物源性细胞外囊泡作为胶质母细胞瘤治疗的天然药物传递平台：在调节肿瘤微环境的同时保持内皮完整性的双重作用

IF 5.2 2区医学 Q1 PHARMACOLOGY & PHARMACY

International Journal of Pharmaceutics: X

Pub Date : 2025-12-01 Epub Date: 2025-06-24 DOI: 10.1016/j.ijpx.2025.100349

Lishan Cui , Giordano Perini , Antonio Minopoli , Valentina Palmieri , Marco De Spirito , Massimiliano Papi

Glioblastoma (GBM) is the most aggressive primary brain tumor, with limited treatment options due to the restrictive blood-brain barrier (BBB) and the heterogeneity of the blood-tumor barrier (BTB). Temozolomide (TMZ), the standard chemotherapy, suffers from poor BBB permeability, rapid degradation, and systemic toxicity. Plant-derived extracellular vesicles (PDEVs) have emerged as promising natural nanocarriers, offering biocompatibility, stability, and the ability to cross biological barriers. This study investigates the use of extracellular vesicles from Citrus limon L. (LDEs) to encapsulate and deliver TMZ (EVs@TMZ) for GBM treatment.

LDEs were isolated, characterized, and loaded with TMZ via ultrasonication. Encapsulation efficiency, stability, and physicochemical properties were assessed using UV–Vis and FTIR spectroscopy. A 3D BTB model was developed using bioprinted U87 glioblastoma cells in Matrigel, co-cultured with hCMEC/D3 endothelial cells to replicate the tumor microenvironment. Barrier integrity was evaluated through TEER and FITC-dextran assays. Uptake, cytotoxicity, and tumor invasion were assessed in this model, along with oxidative stress and VEGF-A secretion.

LDEs effectively encapsulated TMZ, enhancing drug stability under physiological conditions. EVs@TMZ crossed the endothelial barrier while preserving barrier integrity and reducing TMZ-induced ROS production. In the 3D glioblastoma model, EVs@TMZ showed strong cytotoxic effects on tumor cells while minimizing endothelial toxicity and oxidative stress. Moreover, VEGF-A secretion was suppressed, disrupting pro-tumorigenic pathways.

These findings highlight Citrus-derived EVs as biocompatible, efficient carriers for TMZ delivery, offering a promising approach to overcome current challenges in GBM therapy and supporting further development of PDEVs for brain tumor treatment.

胶质母细胞瘤（GBM）是最具侵袭性的原发性脑肿瘤，由于限制性血脑屏障（BBB）和血肿瘤屏障（BTB）的异质性，治疗选择有限。替莫唑胺（TMZ）是标准的化疗药物，具有血脑屏障渗透性差、降解快和全身毒性。植物源性细胞外囊泡（PDEVs）已成为一种很有前途的天然纳米载体，具有生物相容性、稳定性和跨越生物屏障的能力。本研究探讨了利用柑橘柠檬（LDEs）细胞外囊泡包封和递送TMZ （EVs@TMZ）治疗GBM的方法。通过超声分离、表征并加载TMZ。采用紫外可见光谱和红外光谱对其包封效率、稳定性和理化性质进行了评价。利用生物打印的U87胶质母细胞瘤细胞在Matrigel中与hCMEC/D3内皮细胞共培养，复制肿瘤微环境，建立3D BTB模型。通过TEER和fitc -葡聚糖检测评估屏障完整性。在该模型中评估了摄取、细胞毒性和肿瘤侵袭，以及氧化应激和VEGF-A分泌。LDEs有效封装TMZ，提高了药物在生理条件下的稳定性。EVs@TMZ穿过内皮屏障，同时保持屏障完整性并减少tmz诱导的ROS产生。在3D胶质母细胞瘤模型中，EVs@TMZ对肿瘤细胞表现出很强的细胞毒作用，同时最小化内皮毒性和氧化应激。此外，VEGF-A的分泌被抑制，破坏了促肿瘤的途径。这些发现突出了柑橘衍生的ev作为TMZ的生物相容性高效载体，为克服当前GBM治疗中的挑战提供了一种有希望的方法，并支持pdev用于脑肿瘤治疗的进一步开发。

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引用次数: 0

A novel EGFR-targeted photosensitizer for the theranostics of skin cancer 一种用于治疗皮肤癌的新型egfr靶向光敏剂

IF 6.4 2区医学 Q1 PHARMACOLOGY & PHARMACY

International Journal of Pharmaceutics: X

Pub Date : 2025-12-01 Epub Date: 2025-10-09 DOI: 10.1016/j.ijpx.2025.100413

Huijuan Li , Huijun Li , Shuang Qi , Xiaohui Tang , Shiqi Zhao , Xin Bian , Baoqing Tian , Hua Zhang , Yuchun Wei , Dianlong Jia , Xinyue Han , Qing Fan

The epidermal growth factor receptor (EGFR) is a critical therapeutic target implicated in the pathogenesis and progression of skin cancer, holding significant promise for enhancing precision diagnosis and treatment efficacy. In this study, we developed ICG-Z_EGFR, a novel EGFR-targeting agent engineered through conjugation of the photosensitizer indocyanine green (ICG) to an EGFR-targeted dimeric affibody (Z_EGFR) for the theranostics of EGFR-positive skin cancer. In vitro, ICG-Z_EGFR-mediated photothermal therapy (PTT) induced significant cell death in EGFR-positive A431 cells, while exhibiting minimal effects on EGFR-negative MLE-12 cells. Compared to free ICG, ICG-Z_EGFR enhanced tumor retention, and significantly improved tumor-targeting capability, making it advantageous for identifying EGFR-positive tumor tissues. Furthermore, ICG-Z_EGFR also exhibited excellent photothermal conversion performance in vivo, and effectively suppressed the growth of A431 tumors through thermal ablation. Importantly, ICG-Z_EGFR demonstrated favorable short-term safety profiles during the in vivo treatment assay. In conclusion, the successfully developed ICG-Z_EGFR in this study, as a novel tumor-targeted photosensitizer, innovatively breaks through the limitations of traditional single-modal treatment. This study would open up new perspectives and pathways for integrated clinical diagnosis and treatment of EGFR-positive skin cancer.

表皮生长因子受体（epidermal growth factor receptor， EGFR）是参与皮肤癌发病和进展的重要治疗靶点，在提高精准诊断和治疗效果方面具有重要前景。在这项研究中，我们开发了ICG-ZEGFR，这是一种新型的egfr靶向药物，通过将光敏剂吲哚青绿（ICG）与egfr靶向二聚体粘附体（ZEGFR）偶联而设计，用于治疗egfr阳性皮肤癌。在体外，icg - zegfr介导的光热疗法（PTT）在egfr阳性的A431细胞中诱导了显著的细胞死亡，而对egfr阴性的MLE-12细胞的影响微乎其微。与游离ICG相比，ICG- zegfr增强了肿瘤滞留，显著提高了肿瘤靶向能力，有利于识别egfr阳性肿瘤组织。此外，ICG-ZEGFR在体内也表现出优异的光热转化性能，通过热消融有效抑制A431肿瘤的生长。重要的是，在体内治疗试验中，ICG-ZEGFR显示出良好的短期安全性。综上所述，本研究成功开发的ICG-ZEGFR作为一种新型肿瘤靶向光敏剂，创新性地突破了传统单模态治疗的局限性。本研究将为egfr阳性皮肤癌的临床综合诊断和治疗开辟新的视角和途径。

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引用次数: 0

Does the appearance of the Magenstrasse depend on the amount of water consumed? Magenstrasse的外观是否取决于消耗的水量？

IF 5.2 2区医学 Q1 PHARMACOLOGY & PHARMACY

International Journal of Pharmaceutics: X

Pub Date : 2025-12-01 Epub Date: 2025-07-23 DOI: 10.1016/j.ijpx.2025.100365

Linus Großmann , Johanna Cyrus , Stefan Senekowitsch , Toni Wildgrube , Theodora Tzakri , Marie-Luise Kromrey , Werner Weitschies , Michael Grimm

The Magenstrasse (stomach road) is a phenomenon describing the rapid evacuation of water drunken after a solid meal from the stomach. So far, its existence has been demonstrated for water volumes of 150 mL or more. The aim of this three-arm, randomised, cross-over, 12-subject study was to investigate whether the Magenstrasse is also present for smaller water volumes. For this purpose, gastric emptying of 50, 100 or 150 mL of water that was administered after a light meal was determined using MR imaging. With each dose of water, a fast-dissolving compression coated tablet containing caffeine and iron oxide as well as a hard capsule containing stable isotope labelled caffeine and medium-chain triglycerides were administered. This made it possible to determine the initial localization of the respective forms in the stomach on MR images as a function of the amount of water drunk, and also to determine the emptying rates of the two caffeine variants using saliva samples that were obtained in the study and quantified using LC-MS/MS. Gastric emptying of the ingested water was rapid and usually completed after approximately 20 min, regardless of the applied volume. In contrast to the consumed water, gastric emptying of natural caffeine and stable isotope labelled caffeine was delayed. The capsule usually floated on liquid and chyme, whereas the compression coated tablet was often embedded in chyme.

胃路（Magenstrasse）是一种现象，描述了在吃完固体食物后，胃里的水会迅速排出。到目前为止，它的存在已经证明水量为150毫升或更多。这项三臂、随机、交叉、12个受试者的研究的目的是调查Magenstrasse是否也存在于较小的水量中。为此目的，使用磁共振成像确定在清淡餐后给予50,100或150ml水的胃排空。在每一剂水的同时，服用含有咖啡因和氧化铁的速溶压缩包衣片剂，以及含有稳定同位素标记的咖啡因和中链甘油三酯的硬胶囊。这使得在MR图像上确定各自形式在胃中的初始定位成为可能，作为饮水量的函数，并且还可以使用研究中获得的唾液样本确定两种咖啡因变体的排空率，并使用LC-MS/MS进行量化。胃排空摄入的水是迅速的，通常在大约20分钟后完成，无论应用的体积。与消耗的水相比，天然咖啡因和稳定同位素标记的咖啡因的胃排空被延迟。胶囊通常漂浮在液体和食糜上，而压缩包衣片通常嵌入食糜中。

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引用次数: 0

Transformative roles of digital twins from drug discovery to continuous manufacturing: pharmaceutical and biopharmaceutical perspectives 数字双胞胎从药物发现到持续生产的变革作用：制药和生物制药的观点

IF 6.4 2区医学 Q1 PHARMACOLOGY & PHARMACY

International Journal of Pharmaceutics: X

Pub Date : 2025-12-01 Epub Date: 2025-09-27 DOI: 10.1016/j.ijpx.2025.100409

Ravi Maharjan , Nam Ah Kim , Ki Hyun Kim , Seong Hoon Jeong

Digital Twins (DTs) represent a groundbreaking development tool in the pharmaceutical and biopharmaceutical industries, providing virtual representations of physical entities, processes, or systems. This review investigates the transformative roles of DTs by examining their applications throughout the entire drug development lifecycle, from discovery to continuous manufacturing. By facilitating real-time monitoring and predictive analytics, DTs enhance operational efficiency, reduce costs, and improve product quality. Integration with advanced technologies, such as artificial intelligence and machine learning, further amplifies their capabilities, enabling sophisticated data analysis for preventive maintenance and manufacturing optimization. Despite these advantages, the implementation of DTs faces significant challenges, including data integration, model accuracy, and regulatory complexity. This review discusses these barriers while highlighting opportunities for innovation and automation through emerging technologies, including blockchain, nanotechnology, and dark factory. It also explores the potential of DTs to support personalized medicine through individualized treatments based on patient-specific data. Overall, this review highlights the current state, key challenges, and future perspectives of DT applications in pharmaceutical systems, emphasizing their potential to improve efficiency, quality, and patient outcomes.

数字孪生（DTs）代表了制药和生物制药行业突破性的开发工具，提供物理实体、过程或系统的虚拟表示。本文通过检查其在整个药物开发生命周期（从发现到连续生产）中的应用，调查了dt的变革作用。通过促进实时监控和预测分析，dt提高了运营效率，降低了成本，提高了产品质量。与人工智能和机器学习等先进技术的集成，进一步增强了它们的能力，为预防性维护和制造优化提供了复杂的数据分析。尽管有这些优势，但DTs的实施面临着重大挑战，包括数据集成、模型准确性和监管复杂性。本文讨论了这些障碍，同时强调了通过新兴技术（包括区块链、纳米技术和黑暗工厂）实现创新和自动化的机会。它还探讨了直接诊断技术通过基于患者特定数据的个性化治疗来支持个性化医疗的潜力。总的来说，这篇综述强调了DT在制药系统中应用的现状、主要挑战和未来前景，强调了它们在提高效率、质量和患者预后方面的潜力。

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引用次数: 0

Co-assembling de novo designed peptide with high-payload drug protein for noninvasive treatment of corneal neovascularization 新设计肽与高负荷药物蛋白的共组装用于角膜新生血管的无创治疗

IF 6.4 2区医学 Q1 PHARMACOLOGY & PHARMACY

International Journal of Pharmaceutics: X

Pub Date : 2025-12-01 Epub Date: 2025-09-28 DOI: 10.1016/j.ijpx.2025.100410

Yuhua Tong , Sijie Zhou , Yongjie Guo , Xiaoli Jin , Meiting Yu , Chunyun Feng , Hao Chen , Xingjie Zan , Jinyang Li

The specificity and low toxicity of protein drugs are significant for disease treatment but are strongly limited by their weak tissue penetrative capacity. Although formulating proteins with nanoparticle is an alternative strategy, the low encapsulation efficiency (EE) and loading capacity (LC) of protein drugs and their potential for protein inactivation remain significant challenges. Herein, the de novo designed peptide (Arg-His-Cys-Arg-His-Cys-Arg-His-Cys) (RHC)₃, zinc ions (Zn²⁺), and the anti-neovascular protein drug Bevacizumab (Beva) were co-assembled to form PZA@Beva (peptide and Zn²⁺ assemblies encaspsulated Beva) nanomedicine, aiming to overcome the challenges associated with corneal neovascularization (CNV) model. The optimized size of PZA@Beva is approximately 162.5 nm, with EE% and LC% of Beva 92.7 % and 55.8 %, respectively. The bioactivity of encapsulated Beva was preserved, protecting it from proteolytic degradation, and the release of Beva from PZA@Beva exhibited pH-dependent kinetics. In vitro, PZA@Beva demonstrated effective penetration across the ocular barrier via both the paracellular pathway (by opening corneal tight junctions) and the transcellular pathway (through rapid cellular endocytosis). Additionally, PZA@Beva exhibited no cytotoxicity in vitro or in vivo, coupled with prolonged ocular retention, collectively yielding promising results for the treatment of CNV. This study contributes to non-invasive protein delivery across ocular bio-barriers for the treatment of diseases in the anterior segment.

蛋白质药物的特异性和低毒性对疾病治疗具有重要意义，但其组织渗透能力弱，受到强烈限制。虽然用纳米颗粒配制蛋白质是一种替代策略，但蛋白质药物的低封装效率（EE）和负载能力（LC）及其潜在的蛋白质失活仍然是一个重大挑战。本文将从头设计的肽（Arg-His-Cys-Arg-His-Cys-Arg-His-Cys - arg - his - cys）（RHC）3、锌离子（Zn2+）和抗新生血管蛋白药物贝伐单抗（Beva）共组装形成PZA@Beva（肽和Zn2+组装包被Beva）纳米药物，旨在克服与角膜新生血管（CNV）模型相关的挑战。优化后的PZA@Beva尺寸约为162.5 nm， Beva的EE%和LC%分别为92.7%和55.8%。包裹的Beva的生物活性被保留，保护其免受蛋白水解降解，并且从PZA@Beva中释放Beva表现出ph依赖的动力学。在体外，PZA@Beva通过细胞旁通路（通过打开角膜紧密连接）和细胞外通路（通过快速细胞内吞作用）有效穿透眼屏障。此外，PZA@Beva在体外或体内均未表现出细胞毒性，并伴有长时间的眼潴留，这些都为治疗CNV提供了有希望的结果。该研究有助于通过眼生物屏障非侵入性蛋白递送治疗前段疾病。

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引用次数: 0

An overview of advanced nanocarrier systems for Ibrutinib delivery: overcoming pharmacokinetic barriers and enabling targeted cancer therapy 伊鲁替尼递送的先进纳米载体系统概述：克服药代动力学障碍和实现靶向癌症治疗

IF 6.4 2区医学 Q1 PHARMACOLOGY & PHARMACY

International Journal of Pharmaceutics: X

Pub Date : 2025-12-01 Epub Date: 2025-10-11 DOI: 10.1016/j.ijpx.2025.100417

Akshay Shetty, Mahesha Keerikkadu, Pragathi Devanand Bangera, Vamshi Krishna Tippavajhala, Mahalaxmi Rathnanand

Ibrutinib (IBR), a covalent inhibitor of Bruton's tyrosine kinase (BTK), has transformed the treatment of B-cell malignancies like chronic lymphocytic leukemia, mantle cell lymphoma, and Waldenström's macroglobulinemia. With its clinical success, IBR is faced with enormous challenges like low aqueous solubility, low oral bioavailability, extensive first-pass metabolism, off-target toxicities, and resistance development. Nanotechnology-based drug delivery systems have been reported to be effective solutions for these issues. This review offers a comprehensive and critical examination of new trends in IBR-loaded nanocarriers, including PEGylated liposomes, polymeric nanoparticles, dendrimers, solid lipid nanoparticles, nanostructured lipid carriers, and hybrid nanoplatforms. These nanocarriers showed improved drug solubility, prolonged circulation, controlled release, cancer-specific targeting, and reduced systemic toxicity. Emphasis on advanced approaches such as ligand-mediated targeting, stimuli-sensitive release, and co-delivery systems designed to optimize therapeutic effects and avoid resistance mechanisms. Preclinical models demonstrated improved bioavailability, improved tumor accumulation, and improved safety profiles of the IBR nanocarriers. This review covers the translational hurdles, regulatory aspects, and commercial tractability of nanocarrier-mediated inhibition of BTK. In summary, nanotechnology provides a revolutionary pathway for maximizing IBR therapy that could facilitate more efficient, safer, and targeted care for patients with hematologic cancers.

Ibrutinib （IBR）是布鲁顿酪氨酸激酶（BTK）的共价抑制剂，已经改变了b细胞恶性肿瘤如慢性淋巴细胞白血病、套细胞淋巴瘤和Waldenström巨球蛋白血症的治疗。随着临床的成功，IBR面临着巨大的挑战，如低水溶性、低口服生物利用度、广泛的首过代谢、脱靶毒性和耐药性的发展。据报道，基于纳米技术的给药系统是解决这些问题的有效方法。本文综述了装载ibr的纳米载体的新趋势，包括聚乙二醇化脂质体、聚合纳米颗粒、树状大分子、固体脂质纳米颗粒、纳米结构脂质载体和混合纳米平台。这些纳米载体具有改善药物溶解度、延长循环、控制释放、癌症特异性靶向和降低全身毒性的特点。强调先进的方法，如配体介导的靶向，刺激敏感释放和共同递送系统，旨在优化治疗效果和避免耐药机制。临床前模型显示IBR纳米载体提高了生物利用度，改善了肿瘤积累，提高了安全性。本文综述了纳米载体介导的BTK抑制的翻译障碍、调控方面和商业可追溯性。总之，纳米技术为最大化IBR治疗提供了一条革命性的途径，可以促进对血液学癌症患者更有效、更安全、更有针对性的治疗。

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引用次数: 0

Boosting buccal drug absorption: Mechanistic insights into bilosome-mediated delivery 促进口腔药物吸收：生物体介导的给药机制

IF 6.4 2区医学 Q1 PHARMACOLOGY & PHARMACY

International Journal of Pharmaceutics: X

Pub Date : 2025-12-01 Epub Date: 2025-11-11 DOI: 10.1016/j.ijpx.2025.100444

Eleftheria Pantazoglou , Scarlett Zeiringer , Matteo Tollemeto , Nazanin Zanjanizadeh Ezazi , Zhongyang Zhang , Leticia Hosta-Rigau , Jette Jacobsen , Ramona Jeitler , Eva Roblegg , Line Hagner Nielsen

Effective buccal drug delivery is limited by the barrier properties of the mucosa, necessitating innovative systems to enhance permeability without compromising tissue integrity. In this study, bilosomes composed of sodium glycodeoxycholate and phosphatidylcholine were evaluated as a nanoparticulate platform for buccal drug delivery. Their in vitro uptake was investigated using the TR146 buccal cell line. The bilosomes demonstrated stable physicochemical properties and no aggregation. Functional assays indicated that they transiently opened cell-cell junctions, promoting transport across the mucosal barrier while minimizing toxicity. Quartz crystal microbalance with dissipation monitoring confirmed specific interactions with barrier components, supported by observed modulation of desmosomal junctions and cellular uptake. Ex vivo studies using porcine buccal mucosa further showed concentration-dependent distribution. Collectively, these results suggest that bilosomes are a safe and effective platform for enhancing buccal drug absorption.

有效的口腔药物递送受到粘膜屏障特性的限制，需要创新的系统来增强通透性而不损害组织完整性。在这项研究中，由糖脱氧胆酸钠和磷脂酰胆碱组成的胆囊体被评估为口腔药物递送的纳米颗粒平台。用TR146口腔细胞系研究了它们的体外摄取。其物理化学性质稳定，无聚集现象。功能分析表明，它们能瞬间打开细胞-细胞连接，促进通过粘膜屏障的运输，同时将毒性降到最低。带有耗散监测的石英晶体微天平证实了与屏障成分的特定相互作用，这得到了观察到的桥粒连接和细胞摄取调节的支持。利用猪口腔粘膜进行的离体研究进一步显示出浓度依赖性分布。综上所述，这些结果表明，胆囊体是一个安全有效的促进口腔药物吸收的平台。

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引用次数: 0

A blood-brain barrier-penetrating nanoreactor for tumor microenvironment modulation, precise MR imaging and synergistic therapy of glioma 一种用于肿瘤微环境调节、精确磁共振成像和胶质瘤协同治疗的血脑屏障穿透纳米反应器

IF 6.4 2区医学 Q1 PHARMACOLOGY & PHARMACY

International Journal of Pharmaceutics: X

Pub Date : 2025-12-01 Epub Date: 2025-11-17 DOI: 10.1016/j.ijpx.2025.100448

Peipei Dou , Liang Chen , Yiyang Xie , Wenbei Xu , Xinran Zhang , Xiaomei Deng , Haiqing Xu , Jingran Li , Vincent Kawuribi , Shaohui Zheng , Kai Xu , Jing Zhang

Nanomaterials-based theranostic strategy have emerged as innovative techniques for gliomas treatment. However, the existence of blood-brain barrier (BBB) hinders efficient drug delivery to glioma, and the hypoxic condition of tumor microenvironment (TME) significantly reduces therapeutic efficacy. Thus, in this study, we developed a novel reactive oxygen species (ROS)-generating nanoplatform responsive to the TME. This platform utilized mesoporous PtNi nanoparticles (NPs) as carriers, loaded with chelated gadolinium porphyrin (Gd-HMME), to enable combined sonodynamic and chemodynamic therapy under magnetic resonance imaging (MRI) guidance. Employing a transferrin (Tf)-mediated trans-BBB strategy, Tf-PtNi@Gd-HMME-PEG (TPGP) precisely targeted and penetrated glioma tissues, facilitating T1-weighted enhanced imaging of tumor regions. The MRI enhancement signal achieved was 1.64-fold of the control group. Concurrently, the intrinsic acoustic sensitivity and enzyme-like catalytic activity of TPGP produce substantial ROS under ultrasound stimulation. These ROS interact with hydrogen peroxide in the TME to generate toxic free radicals, collectively acting on tumor cells to deliver a dual assault via sonodynamic and chemodynamic mechanisms to effectively inhibit tumor growth and ameliorate the tumor microenvironment. This study underscores the potential of TPGP as a multifunctional nanoplatform for targeted glioma therapy, combining diagnostic imaging with synergistic therapy to overcome the BBB and hypoxic TME.

基于纳米材料的治疗策略已成为胶质瘤治疗的创新技术。然而，血脑屏障（BBB）的存在阻碍了药物对胶质瘤的有效递送，肿瘤微环境（TME）的缺氧状态显著降低了治疗效果。因此，在这项研究中，我们开发了一种新的活性氧（ROS）产生纳米平台响应TME。该平台利用介孔PtNi纳米颗粒（NPs）作为载体，装载螯合钆卟啉（Gd-HMME），在磁共振成像（MRI）指导下实现声动力和化学动力联合治疗。Tf-PtNi@Gd-HMME-PEG （TPGP）采用转铁蛋白（Tf）介导的转血脑屏障策略，精确靶向并穿透胶质瘤组织，促进肿瘤区域的t1加权增强成像。获得的MRI增强信号是对照组的1.64倍。同时，TPGP固有的声敏感性和酶样催化活性在超声刺激下产生大量ROS。这些ROS与TME中的过氧化氢相互作用产生有毒自由基，共同作用于肿瘤细胞，通过声动力和化学动力机制提供双重攻击，有效抑制肿瘤生长，改善肿瘤微环境。这项研究强调了TPGP作为靶向胶质瘤治疗的多功能纳米平台的潜力，将诊断成像与协同治疗相结合，以克服血脑屏障和缺氧TME。

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