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

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 : 2025-09-27 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

Nanocarrier-based immunotherapy for viral diseases 基于纳米载体的病毒性疾病免疫治疗

IF 6.4 2区医学 Q1 PHARMACOLOGY & PHARMACY

International Journal of Pharmaceutics: X

Pub Date : 2025-09-26 DOI: 10.1016/j.ijpx.2025.100408

Dan Liu , Te Zhao , Yi Li , Lin Huang , Junwei Che , Pengfei Zou , Wenjie Yang , Junjie Ding , Pinghui Wu , Xiang Gao , Yuhua Ran , Hua Sun , Zhiping Li , Jing Gao , Chunsheng Gao

The global morbidity and mortality associated with viral diseases pose a major threat to public health security and cause significant economic losses worldwide. Developing novel prophylactic and therapeutic interventions remains an urgent priority in contemporary virology research. Immunotherapy, initially developed for cancer treatment, has shown satisfactory efficacy in the management of viral infections. However, the clinical application of immunotherapy is still constrained by its inherent limitations, including poor stability, inadequate targeting ability, and systemic toxicity. Nanocarriers have emerged as a promising platform to address these challenges, with features such as protecting active substances from enzymatic degradation, delivering active substances specifically to the site of infection via ligand modification, and controlling the release behavior of active substances so as to maintain their controlled and therapeutic concentrations. Therefore, the combination of immunotherapy and nanocarriers is expected to overcome the shortcomings of immunotherapy and significantly improve their therapeutic efficacy. In this review, the classification, application, and combination of immunotherapy with nanocarriers in viral diseases are summarized. The challenges and the future prospects of this combination are also discussed.

与病毒性疾病相关的全球发病率和死亡率对公共卫生安全构成重大威胁，并在世界范围内造成重大经济损失。开发新的预防和治疗干预措施仍然是当代病毒学研究的当务之急。免疫疗法最初是为癌症治疗而开发的，在治疗病毒感染方面显示出令人满意的疗效。然而，免疫疗法的临床应用仍然受到其固有局限性的制约，包括稳定性差、靶向能力不足以及全身毒性。纳米载体已经成为解决这些挑战的一个有希望的平台，其特点包括保护活性物质免受酶降解，通过配体修饰将活性物质特异性地递送到感染部位，以及控制活性物质的释放行为以保持其控制和治疗浓度。因此，免疫治疗与纳米载体的结合有望克服免疫治疗的不足，显著提高其治疗效果。本文就纳米载体免疫治疗在病毒性疾病中的分类、应用及联合应用作一综述。并对该组合面临的挑战和未来前景进行了讨论。

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引用次数: 0

Colistin and Oxyclozanide co-loaded PLGA nano-microspheres to reverse colistin resistance can effectively treat colistin-resistant Escherichia coli infections 粘菌素与羟氯胺共载PLGA纳米微球逆转粘菌素耐药，可有效治疗耐粘菌素大肠杆菌感染

IF 6.4 2区医学 Q1 PHARMACOLOGY & PHARMACY

International Journal of Pharmaceutics: X

Pub Date : 2025-09-25 DOI: 10.1016/j.ijpx.2025.100402

Shuai-hua Li , Meng-jing Feng , Hao-tian Shao , Jian-hua Liu, Hua Wu, Li Yuan, Xiao-yuan Ma, Gong-zheng Hu

Colistin (COL) is widely recognized as the last line of defense for treating MDR-negative bacterial infections, but currently, bacteria have a very serious resistance to COL. The combination of antibacterial drugs and adjuvant drugs can reverse drug resistance, enhance antibacterial activity, and improve therapeutic effects. It is currently regarded as a new safe and effective strategy for controlling drug resistance. In this study, we found that the combination of Oxyclozanide (OXY) and colistin can effectively reverse colistin resistance. For multiple colistin resistant Escherichia coli (E. coli) strains, COL-OXY-PLGA @MS significantly reduced the MIC of COL monotherapy (8 < MIC<64) by 40–160 times. The prepared COL-OXY-PLGA@MS had particle sizes of 140–160 nm, PDI of 0.03–0.2, COL loading of 5.14 % and OXY loading of 2.93 %. The release rate of COL in COL-OXY-PLGA@MS at 72 h was 39.31 %, and there was no burst release. Cytotoxicity assay, hemolysis test and long-term injection tests in mice have proved that COL-OXY-PLGA@MS has good safety and biocompatibility. It was clearly observed by SEM that the COL-OXY-PLGA@MS group disrupted E. coli 58 cells under 1 h of action with obvious exudation of contents, and large number of cells ruptured at 4 h and 12 h. COL-OXY-PLGA@MS significantly reduced mortality rate after E. coli infection in mice. This study successfully prepared COL-OXY-PLGA@MS with high safety and strong antibacterial effect, which has great potential in the treatment of infections caused by color-resistant Gram-negative bacteria and provides a new and important strategy for the clinical application of colistin.

粘菌素（COL）被广泛认为是治疗耐多药阴性细菌感染的最后一道防线，但目前细菌对COL的耐药非常严重，抗菌药物与辅助药物联合使用可以逆转耐药，增强抗菌活性，提高治疗效果。目前被认为是一种安全有效的控制耐药新策略。本研究发现氧氯胺（Oxyclozanide， OXY）与粘菌素联合用药可有效逆转粘菌素耐药性。对于多重粘菌素耐药的大肠杆菌（E. coli）菌株，COL- oxy - plga @MS显著降低COL单药治疗的MIC (8 < MIC<64) 40-160倍。制备的COL-OXY-PLGA@MS粒径为140 ~ 160 nm， PDI为0.03 ~ 0.2，冷负荷为5.14%，氧负荷为2.93%。COL-OXY-PLGA@MS中COL在72 h的释放率为39.31%，无爆发性释放。细胞毒性试验、溶血试验和小鼠长期注射试验证明COL-OXY-PLGA@MS具有良好的安全性和生物相容性。扫描电镜清楚地观察到COL-OXY-PLGA@MS组在作用1 h时破坏了大肠杆菌58个细胞，内容物明显渗出，在4 h和12 h时大量细胞破裂COL-OXY-PLGA@MS显著降低了小鼠感染大肠杆菌后的死亡率。本研究成功制备出安全性高、抗菌效果强的COL-OXY-PLGA@MS，在治疗耐色革兰氏阴性菌感染方面具有很大潜力，为粘菌素的临床应用提供了新的重要策略。

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引用次数: 0

Chondroitin sulfate-decorated cupper-benzene dicarboxylate framework as an efficient passive and active targeting nanomedicine for anticancer methotrexate delivery 硫酸软骨素修饰铜-二羧酸苯框架作为一种高效的抗甲氨蝶呤靶向纳米药物

IF 6.4 2区医学 Q1 PHARMACOLOGY & PHARMACY

International Journal of Pharmaceutics: X

Pub Date : 2025-09-25 DOI: 10.1016/j.ijpx.2025.100403

Siamak Javanbakht, Reza Mohammadi

In this research, an advanced drug delivery system was developed by decorating the copper-benzene dicarboxylate framework (Cu(BDC)) with the multifunctional chondroitin sulfate (ChS), termed Cu(BDC)/ChS. This novel system is designed for both active and passive targeting, featuring a pH-sensitive release mechanism that enhances drug effectiveness. Different characterization techniques confirmed the successful synthesis of the Cu(BDC)/ChS nanocomposite. In-vitro experiments evaluating the loading and release of methotrexate (MTX) showed that the release rate was significantly higher at pH 4.5, releasing 70 % over 92 h at 41 °C, in contrast to less than 20 % at pH 7.4 at 37 °C. This pH responsiveness of the Cu(BDC)/ChS promotes drug release in environments alike to tumor tissues. Additionally, cytotoxicity tests revealed that MTX-loaded Cu(BDC)/ChS exhibited considerable cytotoxic effects on MCF-7 cancer cells, with IC50 value of ∼250 μg/mL after 48 h, accompanied by an increase in apoptosis rates. Remarkably, the overexpression of CD44 receptors on cancer cell surfaces underscores the significance of ChS-functionalized systems in promoting selective cancer cell apoptosis, while exhibiting minimal cytotoxicity toward normal HUVEC cells. Overall, the findings indicate that the combination of Cu(BDC) and ChS holds promise for developing effective platforms for anticancer drug delivery.

本研究利用多功能硫酸软骨素（ChS）（Cu(BDC) /ChS）修饰铜-苯二羧酸盐框架（Cu(BDC)），构建了一种新型给药系统。这种新型系统设计用于主动和被动靶向，具有ph敏感释放机制，提高药物有效性。不同的表征技术证实了Cu(BDC)/ChS纳米复合材料的成功合成。体外实验评估了甲氨蝶呤（MTX）的负载和释放，结果表明，在pH为4.5时，释出率显著提高，在41°C下，92 h内释出率为70%，而在pH为7.4时，37°C下释出率低于20%。Cu(BDC)/ChS的这种pH响应性促进药物在类似于肿瘤组织的环境中释放。此外，细胞毒性试验显示，mtx负载Cu(BDC)/ChS对MCF-7癌细胞具有相当大的细胞毒性作用，48 h后IC50值为~ 250 μg/mL，并伴有凋亡率增加。值得注意的是，CD44受体在癌细胞表面的过度表达强调了chs功能化系统在促进选择性癌细胞凋亡中的重要性，同时对正常HUVEC细胞表现出最小的细胞毒性。总的来说，研究结果表明，Cu（BDC）和ChS的结合有望开发有效的抗癌药物传递平台。

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引用次数: 0

Foamable pluroleosomes system loaded with amlodipine as a repurposed antibacterial topical formulation against MRSA-induced infection; optimization, in-vitro, ex-vivo, and in-vivo studies 负载氨氯地平的泡沫多聚体系统作为抗mrsa诱导感染的重新用途抗菌外用制剂优化，体外，离体和体内研究

IF 6.4 2区医学 Q1 PHARMACOLOGY & PHARMACY

International Journal of Pharmaceutics: X

Pub Date : 2025-09-24 DOI: 10.1016/j.ijpx.2025.100406

Alaa S. Eita , Amna M.A. Makky , Asem Anter , Islam A. Khalil

Amlodipine besylate (AML) is a renowned antihypertensive drug currently acknowledged for having antibacterial activity. AML repositioning can be helpful in the defeat of microbial-resistant strains. Loading amlodipine in the pluroleosomes (PLOs) foam system is desired to approach innovative remedies with a convenient application capable of targeting deep infections. The mixture design was employed to generate different pluroleosomes formulations consisting of various ratios of Pluronic F-127, oleic acid, and soya lecithin loaded with amlodipine. Based on the desirability function, the selected optimized formula (AML-PLOs), consisting of 4.875 for lecithin, one for oleic acid, and 1.125 for pluronic, exhibits a particle size of 320.56 ± 15.5 nm, a polydispersity index of 0.4461 ± 0.03, a surface charge of 15.261 ± 0.62 mV, and AML entrapment of 71.25 ± 3.52 %. The morphological image displayed a uniform spherical shape at the nanoscale. In addition, thermal analysis and infrared spectroscopy (IR) proved the suitability of AML-pluroleosome vesicles. Tween 20, the selected nonionic surfactant in foam preparation, achieved the demand values of foam parameters and showed adequate stability upon storage for up to 90 days. The selected AML-PLO foam showed complete AML release after 48 h in a controlled manner, and the cumulative amount permeated after 24 h was about 45 %. Efficient penetration through dermal strata was affirmed by utilizing a confocal microscope. In vitro microbiological assay, besides the in vivo microbiological and histopathological studies employing a wound healing model, validated the antibacterial efficacy of amlodipine. Those outcomes demonstrated that the prepared pluroleosome foam system of AML is a competent candidate for combating topical bacterial infection.

苯磺酸氨氯地平（AML）是一种著名的抗高血压药物，目前公认具有抗菌活性。AML重新定位可能有助于击败微生物耐药菌株。在多聚体（PLOs）泡沫系统中加载氨氯地平是一种创新的疗法，具有方便的应用能力，能够靶向深度感染。采用混合设计制备了由不同比例的Pluronic F-127、油酸和大豆卵磷脂负载氨氯地平组成的多聚体配方。优选出的优化配方（AML- plos）为卵磷脂（4.875）、油酸(1)、pluronic(1.125)，粒径为320.56±15.5 nm，多分散性指数为0.4461±0.03，表面电荷为15.261±0.62 mV， AML包载率为71.25±3.52%。形态学图像在纳米尺度上呈现均匀的球形。此外，热分析和红外光谱（IR）证实了aml -多聚体囊泡的适用性。泡沫制备中选用的非离子表面活性剂Tween - 20达到了泡沫参数的要求值，并在长达90天的储存中表现出足够的稳定性。所选择的AML- plo泡沫在48 h后可控制地完全释放AML， 24 h后的累积渗透量约为45%。利用共聚焦显微镜确认有效穿透真皮层。体外微生物学分析以及采用伤口愈合模型的体内微生物学和组织病理学研究验证了氨氯地平的抗菌效果。这些结果表明，制备的AML多聚体泡沫体系是对抗局部细菌感染的有效候选物。

{"title":"Foamable pluroleosomes system loaded with amlodipine as a repurposed antibacterial topical formulation against MRSA-induced infection; optimization, in-vitro, ex-vivo, and in-vivo studies","authors":"Alaa S. Eita , Amna M.A. Makky , Asem Anter , Islam A. Khalil","doi":"10.1016/j.ijpx.2025.100406","DOIUrl":"10.1016/j.ijpx.2025.100406","url":null,"abstract":"<div><div>Amlodipine besylate (AML) is a renowned antihypertensive drug currently acknowledged for having antibacterial activity. AML repositioning can be helpful in the defeat of microbial-resistant strains. Loading amlodipine in the pluroleosomes (PLOs) foam system is desired to approach innovative remedies with a convenient application capable of targeting deep infections. The mixture design was employed to generate different pluroleosomes formulations consisting of various ratios of Pluronic F-127, oleic acid, and soya lecithin loaded with amlodipine. Based on the desirability function, the selected optimized formula (AML-PLOs), consisting of 4.875 for lecithin, one for oleic acid, and 1.125 for pluronic, exhibits a particle size of 320.56 ± 15.5 nm, a polydispersity index of 0.4461 ± 0.03, a surface charge of 15.261 ± 0.62 mV, and AML entrapment of 71.25 ± 3.52 %. The morphological image displayed a uniform spherical shape at the nanoscale. In addition, thermal analysis and infrared spectroscopy (IR) proved the suitability of AML-pluroleosome vesicles. Tween 20, the selected nonionic surfactant in foam preparation, achieved the demand values of foam parameters and showed adequate stability upon storage for up to 90 days. The selected AML-PLO foam showed complete AML release after 48 h in a controlled manner, and the cumulative amount permeated after 24 h was about 45 %. Efficient penetration through dermal strata was affirmed by utilizing a confocal microscope. <em>In vitro</em> microbiological assay, besides the <em>in vivo</em> microbiological and histopathological studies employing a wound healing model, validated the antibacterial efficacy of amlodipine. Those outcomes demonstrated that the prepared pluroleosome foam system of AML is a competent candidate for combating topical bacterial infection.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"10 ","pages":"Article 100406"},"PeriodicalIF":6.4,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145216956","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A self-delivery albumin nanomedicine amplified photodynamic therapy against esophageal cancer through COX-2/PGE2 interruption and regulation of mitochondrial respiratory 自释白蛋白纳米药物通过阻断COX-2/PGE2和调节线粒体呼吸增强光动力治疗食管癌

IF 6.4 2区医学 Q1 PHARMACOLOGY & PHARMACY

International Journal of Pharmaceutics: X

Pub Date : 2025-09-24 DOI: 10.1016/j.ijpx.2025.100407

Shiying Xu , Lina Wu , Boxin Chen , Xiaoliang Deng , Zhihui Zheng , Fei Wu , Lingjun Zeng , Changqing Zheng , Xiaomu Hu , Aiwen Huang , Xin Zhou , Xianquan Feng , Zhihong Liu

Photodynamic therapy (PDT) has emerged as a promising non-invasive cancer treatment due to its selective tumor ablation and excellent safety characteristics. However, its efficacy is limited by tumor hypoxia and excessive inflammation. In this study, we fabricated human serum albumin-based nanoparticles (CAI NPs) encapsulating celecoxib (CXB), atovaquone (ATO), and IR820 via sonication. The CAI NPs exhibited favorable physicochemical properties, including a uniform size distribution (<200 nm), high encapsulation efficiency and excellent colloidal stability. Initially, ATO acts as a mitochondrial complex III inhibitor, suppressing oxidative phosphorylation to ameliorate tumor hypoxia. This hypoxia alleviation potentiates PDT efficacy by enhancing tumor cell ROS generation. Furthermore, concomitant COX-2/PGE2 inhibition by CXB attenuates the excessive inflammatory cascade triggered during PDT, resulting in enhanced therapeutic outcomes through microenvironment modulation. Eventually, the dual-enhanced CAI NPs demonstrate potent antitumor activity in both in vivo and ex vivo models, while maintaining excellent biocompatibility under physiological conditions. In summary, the integrated three-drug regimen conclusively enhances photodynamic therapeutic outcomes through multimodal mechanisms, establishing a viable treatment approach for esophageal cancer.

光动力疗法（PDT）因其选择性消融肿瘤和良好的安全性而成为一种很有前途的非侵入性癌症治疗方法。但其疗效受肿瘤缺氧和过度炎症的限制。在这项研究中，我们通过超声制备了基于人血清白蛋白的纳米颗粒（CAI NPs），该纳米颗粒包被塞来昔布（CXB）、阿托伐醌（ATO）和IR820。CAI纳米粒子具有良好的物理化学性质，包括粒径分布均匀（约200 nm）、包封效率高和胶体稳定性好。最初，ATO作为线粒体复合物III抑制剂，抑制氧化磷酸化以改善肿瘤缺氧。这种缺氧缓解通过增强肿瘤细胞ROS的产生来增强PDT的疗效。此外，CXB同时抑制COX-2/PGE2可减轻PDT期间引发的过度炎症级联反应，通过微环境调节提高治疗效果。最终，双增强CAI NPs在体内和离体模型中都显示出强大的抗肿瘤活性，同时在生理条件下保持良好的生物相容性。综上所述，三药联合方案通过多模式机制提高了光动力治疗效果，为食管癌的治疗建立了可行的方法。

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引用次数: 0

Investigation of differences in mechanisms of die filling between a compaction simulator and a rotary press 压实模拟器和轮转压力机充模机制差异的研究

IF 6.4 2区医学 Q1 PHARMACOLOGY & PHARMACY

International Journal of Pharmaceutics: X

Pub Date : 2025-09-23 DOI: 10.1016/j.ijpx.2025.100405

Ben Kohlhaas , Jan Henrik Finke

Die Filling is the critical process step in tableting as it determines the tablet weight and its variability as well as impacting tablet strength and defect propensity. Several studies have focused on modeling die filling on rotary presses, however none have investigated the matter on a compaction simulator. Therefore, the aim of this study is to characterize the die filling behavior on a compaction simulator and compare it to a laboratory scale rotary press. Special attention is paid to the complex interplay of process parameters, machine geometry and material properties. Experimental results are supported by a newly introduced physics-based calculation of the course of the exerted differential pressure as a main driver of die filling. On the compaction simulator, suction filling is shown to be more intense due to its geometry and elevated lower punch velocities, rendering paddle speed of the feed frame less crucial. On the rotary press, paddle rotation is necessary to ensure sufficient powder flow into the dies, especially at high production speed, due to a shorter filling time. An alternative fill cam geometry, where the punch is already pulled down to a certain extent before entering the feed frame, reduces the exerted suction pressure in the filling zone, giving generally lower filling yield for materials of limited flowability. The study offers a solid understanding of die filling on a compaction simulator and the underlying mechanisms. Together with the comparative experiments, the foundation for a model for rational scale transfer towards rotary presses is established.

充模是压片的关键工艺步骤，因为它决定了片剂的重量及其变化，并影响片剂的强度和缺陷倾向。有几项研究集中在旋转压力机的模具填充建模上，但是没有人在压实模拟器上调查此事。因此，本研究的目的是在压实模拟器上表征模具填充行为，并将其与实验室规模的旋转压力机进行比较。特别注意的是复杂的相互作用的工艺参数，机器的几何形状和材料的性质。实验结果得到了新引入的基于物理的压差过程计算的支持，压差是模具填充的主要驱动因素。在压实模拟器上，由于其几何形状和提高的低冲孔速度，吸气填充显示出更强的强度，使得进料框的桨速不那么重要。在轮转印刷机上，由于填充时间较短，桨叶旋转是必要的，以确保足够的粉末流入模具，特别是在高生产速度下。另一种填充凸轮几何形状，即冲头在进入料框之前已经向下拉到一定程度，减少了填充区施加的吸入压力，对于流动性有限的材料，通常会产生较低的填充率。该研究提供了一个坚实的理解压实模拟器上的模具填充和潜在的机制。结合对比实验，建立了旋压机合理尺度传递模型的基础。

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引用次数: 0

Cell membrane-camouflaged nanomedicines for enhanced thrombolysis and blood-brain barrier penetration in ischemic stroke therapy 在缺血性脑卒中治疗中增强溶栓和血脑屏障穿透的细胞膜伪装纳米药物

IF 6.4 2区医学 Q1 PHARMACOLOGY & PHARMACY

International Journal of Pharmaceutics: X

Pub Date : 2025-09-20 DOI: 10.1016/j.ijpx.2025.100404

Xiachan Chen , Yiming Liu , Jing Zou , Hao Chen , Hengrui Zhang , Yan Guo , Xingjie Zan

Thrombus-induced ischemic stroke (IS) remains a serious threat a serious health threat with limited therapeutic efficacy due to the dual challenges of precise thrombus targeting and restricted blood-brain barrier (BBB) penetration. While conventional nanocarriers, such as liposomes, micelles, and polymeric nanoparticles (NPs), demonstrate clinical potential due to their mature preparation protocols, their application is limited by poor targeting accuracy, inadequate biocompatibility, and rapid systemic clearance. In response, microenvironment-responsive biomimetic drug delivery systems based on cell membrane-camouflaged nanomedicines (CM-NMs) have emerged as a promising strategy, leveraging the pathological features of ischemic lesions for enhanced targeting and treatment. CM-NMs stand out by utilizing cell membranes to preserve innate targeting and/or BBB penetration capabilities. This approach also ensures high biocompatibility and minimizes the risk of immune clearance. This review highlights recent advances in CM-NMs for IS treatment, critically discussing three key approaches: (1) platelet membrane-camouflaged nanomedicines (PLM-NMs), which mimic platelet adhesion for thrombus-specific accumulation, (2) immune cell membrane NMs and stem cell membrane NMs, which leverage inflammatory tropism or homing mechanisms for enhanced BBB penetration, and (3) hybrid membrane NMs, which enable multi-targeting capabilities. Furthermore, we discuss ongoing challenges and clinical translation potential of CM-NMs to provide guidance for next-generation CM-NMs.

血栓诱导的缺血性卒中（IS）仍然是一个严重的健康威胁，由于血栓精确靶向和血脑屏障（BBB）穿透受限的双重挑战，治疗效果有限。虽然传统的纳米载体，如脂质体、胶束和聚合物纳米颗粒（NPs），由于其成熟的制备方案而显示出临床潜力，但它们的应用受到靶向准确性差、生物相容性不足和快速全身清除的限制。因此，基于细胞膜伪装纳米药物（CM-NMs）的微环境响应仿生药物递送系统已经成为一种有前途的策略，利用缺血性病变的病理特征来增强靶向和治疗。CM-NMs通过利用细胞膜来保持固有的靶向和/或血脑屏障穿透能力而脱颖而出。这种方法还确保了高生物相容性，并将免疫清除的风险降至最低。本文综述了CM-NMs治疗IS的最新进展，并重点讨论了三种关键方法：(1)血小板膜伪装纳米药物（PLM-NMs），它模拟血小板粘附形成血栓特异性积累；(2)免疫细胞膜NMs和干细胞膜NMs，利用炎症趋向性或归巢机制增强血脑屏障渗透；(3)混合膜NMs，它具有多靶向能力。此外，我们讨论了CM-NMs正在面临的挑战和临床转化潜力，为下一代CM-NMs提供指导。

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引用次数: 0

Retraction notice to "Corrigendum to "Impact of polymer chemistry on critical quality attributes of selective laser sintering 3D printed solid oral dosage forms" [International Journal of Pharmaceutics:X Volume 6 (2023) 100203] [International Journal of Pharmaceutics: X 9 (2025) 100319]. 对“聚合物化学对选择性激光烧结3D打印固体口服剂型的关键质量属性的影响”的更正的撤回通知[International Journal of Pharmaceutics:X Volume 6 (2023) 100203] [International Journal of Pharmaceutics:X 9(2025) 100319]。

IF 6.4 2区医学 Q1 PHARMACOLOGY & PHARMACY

International Journal of Pharmaceutics: X

Pub Date : 2025-09-19 eCollection Date: 2025-12-01 DOI: 10.1016/j.ijpx.2025.100388

Evgenii Tikhomirov, Valerie Levine, Michelle Åhlén, Nicole Di Gallo, Maria Strømme, Thomas Kipping, Julian Quodbach, Jonas Lindh

[This retracts the article DOI: 10.1016/j.ijpx.2025.100319.][This retracts the article DOI: 10.1016/j.ijpx.2023.100203.].

[这更正了文章DOI: 10.1016/j.ijpx.2025.100319。][更正文章DOI: 10.1016/j.ijpx.2023.100203.]

引用次数: 0

Electrospinning of animal-free derived collagen-like protein: Development and characterization of VECOLLAN®- nanofibers for biomedical applications 静电纺丝无动物源类胶原蛋白：VECOLLAN®-生物医学应用纳米纤维的开发和表征

IF 6.4 2区医学 Q1 PHARMACOLOGY & PHARMACY

International Journal of Pharmaceutics: X

Pub Date : 2025-09-19 DOI: 10.1016/j.ijpx.2025.100398

Christoph Krauss , Maria Montero Mirabet , Jian-Feng Zhang , Karsten Mäder

This study investigates the potential of VECOLLAN®, a recombinant, novel, non-animal-derived collagen-like protein, for use in electrospinning applications relevant to biomedical and drug delivery sectors. Given the limitations of animal-derived collagens, including immunogenicity and variability, VECOLLAN® offers a promising alternative due to its biotechnological production and non-immunogenic, non-allergenic, and non-inflammatory properties. We optimized the electrospinning parameters for VECOLLAN® and examined the effects of a novel coaxial crosslinking approach on the dissolution and disintegration behaviors of the resultant fibers. Our results demonstrate that VECOLLAN®-based fibers can achieve varying degrees of water insolubility, influenced by crosslinker concentration and type of crosslinker. Additionally, the fibers exhibit distinct swelling behaviors. With the addition of hyaluronic acid, the water absorption capacity could be increased. We investigated the distribution of silver nanoparticles within the fibers, confirming the homogeneity of the coaxial electrospinning process. Mechanical tests revealed that increased crosslinker concentrations lead to greater stability and rigidity, while elastin incorporation improved elongation properties. This study lays the groundwork for developing electrospun fibers made from a non-animal-derived collagen-like protein, highlighting the potential for applications in drug delivery and tissue engineering. Future research should focus on assessing the biocompatibility of these fibers further to explore their utility as drug carriers or cell scaffolds. Overall, our findings underscore the promising properties of VECOLLAN®-based fibers in advancing innovative solutions in the biomedical and drug delivery sectors.

VECOLLAN是一种重组的、新型的、非动物来源的胶原样蛋白，该蛋白可用于生物医学和药物输送领域的静电纺丝应用。考虑到动物源性胶原蛋白的局限性，包括免疫原性和可变性，VECOLLAN®由于其生物技术生产和非免疫原性、非过敏性和非炎症性，提供了一个有希望的替代方案。我们优化了VECOLLAN®的静电纺丝参数，并研究了一种新型同轴交联方法对所得纤维溶解和解体行为的影响。我们的研究结果表明，基于VECOLLAN®的纤维可以实现不同程度的不水溶性，受交联剂浓度和交联剂类型的影响。此外，纤维表现出明显的膨胀行为。透明质酸的加入可提高其吸水能力。我们研究了银纳米粒子在纤维中的分布，证实了同轴静电纺丝过程的均匀性。力学试验表明，增加交联剂浓度可提高稳定性和刚性，而弹性蛋白掺入可提高延伸性能。这项研究为开发由非动物源性胶原样蛋白制成的电纺丝纤维奠定了基础，突出了在药物输送和组织工程中的应用潜力。未来的研究应侧重于进一步评估这些纤维的生物相容性，以探索其作为药物载体或细胞支架的用途。总的来说，我们的研究结果强调了基于VECOLLAN®的纤维在推进生物医学和药物输送领域的创新解决方案方面的前景。

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