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Drug delivery using gold nanoparticles 利用金纳米颗粒给药
IF 15.2 1区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2024-11-29 DOI: 10.1016/j.addr.2024.115481
Lev Dykman , Boris Khlebtsov , Nikolai Khlebtsov
Modern nanotechnologies provide various possibilities for efficiently delivering drugs to biological targets. This review focuses on using functionalized gold nanoparticles (GNPs) as a drug delivery platform. Owing to their exceptional size and surface characteristics, GNPs are a perfect drug delivery vehicle for targeted and selective distribution. Several in vitro and in vivo tests have shown how simple it is to tailor these particles to administer chemical medications straight to tumors. The GNP surface can also be coated with ligands to modify drug release or improve selectivity. Moreover, the pharmacological activity can be enhanced by using the photothermal characteristics of the particles.
现代纳米技术为有效地将药物输送到生物靶点提供了多种可能性。本文综述了功能化金纳米颗粒(GNPs)作为给药平台的研究进展。由于其特殊的尺寸和表面特性,GNPs是一种完美的靶向和选择性分配药物的载体。几项体外和体内试验表明,定制这些颗粒,将化学药物直接施用于肿瘤是多么简单。GNP表面也可以涂覆配体以修饰药物释放或提高选择性。此外,利用颗粒的光热特性可以增强药理学活性。
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引用次数: 0
Biopharmaceutical drug delivery and phototherapy using protein crystals 利用蛋白质晶体进行生物制药给药和光疗
IF 15.2 1区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2024-11-28 DOI: 10.1016/j.addr.2024.115480
Renbin Zhou , Jinghan Qu , Xuejiao Liu , Fangrui Lin , Tymish Y. Ohulchanskyy , Nuernisha Alifu , Junle Qu , Da-Chuan Yin
Biopharmaceutical drugs, including proteins, peptides, and antibodies, are renowned for their high specificity and efficacy, fundamentally transforming disease treatment paradigms. However, their structural complexity presents challenges for their formulation and delivery. Protein crystals, characterized by high purity, high stability and a porous structure for biopharmaceutical drug encapsulation, providing a potential avenue for formulating and delivering biopharmaceutical drugs. There is increasing interest in engineering protein crystals to delivery biopharmaceutical drugs for biomedical applications. This review summarizes the recent advances in biopharmaceutical drug delivery and phototherapy using protein crystals. First, we evaluate the advantages of using protein crystals for biopharmaceutical drugs delivery. Next, we outline the strategies for in vitro and in vivo crystallization to prepare protein crystals. Importantly, the review highlights the advanced applications of protein crystals in biopharmaceutical drug delivery, tumor phototherapy, and other optical fields. Finally, it provides insights into future perspectives of biopharmaceutical drug delivery using protein crystals. This comprehensive review aims to provide effective insights into design of protein crystals to simplify biopharmaceutical drug delivery and improve disease treatment.
生物制药药物(包括蛋白质、肽和抗体)以其高度特异性和疗效而著称,从根本上改变了疾病治疗模式。然而,其结构的复杂性给药物的配制和输送带来了挑战。蛋白质晶体具有高纯度、高稳定性和多孔结构等特点,可用于生物制药药物的封装,为生物制药药物的配制和输送提供了一条潜在的途径。人们对利用蛋白质晶体工程技术为生物医学应用输送生物制药药物的兴趣与日俱增。本综述总结了利用蛋白质晶体进行生物制药给药和光疗的最新进展。首先,我们评估了使用蛋白质晶体输送生物制药药物的优势。接着,我们概述了体外和体内结晶制备蛋白质晶体的策略。重要的是,这篇综述强调了蛋白质晶体在生物制药给药、肿瘤光疗和其他光学领域的先进应用。最后,综述还对使用蛋白质晶体进行生物制药给药的未来前景进行了展望。这篇全面的综述旨在为简化生物制药给药和改善疾病治疗提供有效的蛋白质晶体设计见解。
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引用次数: 0
3D printing of drug delivery systems enhanced with micro/nano-technology 利用微/纳米技术增强给药系统的 3D 打印技术
IF 15.2 1区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2024-11-26 DOI: 10.1016/j.addr.2024.115479
Hui Zhu , Huijuan Kuang , Xinxin Huang , Xiao Li , Ruosen Zhao , Guojin Shang , Ziyu Wang , Yucheng Liao , Jiankang He , Dichen Li
Drug delivery systems (DDSs) are increasingly important in ensuring drug safety and enhancing therapeutic efficacy. Micro/nano-technology has been utilized to develop DDSs for achieving high stability, bioavailability, and drug efficiency, as well as targeted delivery; meanwhile, 3D printing technology has made it possible to tailor DDSs with diverse components and intricate structures. This review presents the latest research progress integrating 3D printing technology and micro/nano-technology for developing novel DDSs. The technological fundamentals of 3D printing technology supporting the development of DDSs are presented, mainly from the perspective of different 3D printing mechanisms. Distinct types of DDSs leveraging 3D printing and micro/nano-technology are analyzed deeply, featuring micro/nanoscale materials and structures to enrich functionalities and improve effectiveness. Finally, we will discuss the future directions of 3D-printed DDSs integrated with micro/nano-technology, focusing on technological innovation and clinical application. This review will support interdisciplinary research efforts to advance drug delivery technology.
给药系统(DDS)在确保药物安全和提高疗效方面的作用日益重要。微/纳米技术已被用于开发药物递送系统,以实现高稳定性、生物利用度和药物效率,以及靶向递送;同时,三维打印技术已使定制具有不同成分和复杂结构的药物递送系统成为可能。本综述介绍了结合三维打印技术和微米/纳米技术开发新型 DDS 的最新研究进展。主要从不同三维打印机制的角度介绍了支持 DDS 开发的三维打印技术的技术基础。深入分析了利用三维打印和微米/纳米技术开发的不同类型的 DDS,其特点是采用微米/纳米级材料和结构来丰富功能和提高效能。最后,我们将讨论三维打印 DDS 与微/纳米技术结合的未来发展方向,重点关注技术创新和临床应用。本综述将支持跨学科研究工作,推动给药技术的发展。
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引用次数: 0
Integrated pharmacokinetic-pharmacodynamic and agent-based modelling in drug development: Current status and future perspectives 药物开发中的药代动力学-药效学和基于代理的综合建模:现状与未来展望
IF 15.2 1区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2024-11-23 DOI: 10.1016/j.addr.2024.115474
James W.T. Yates
In the past two decades, quantitative mathematical modelling approaches have emerged as a paradigm to improve new drug research productivity, especially the application of pharmacokinetic-pharmacodynamic and quantitative systems pharmacology modelling. These approaches have largely made use of deterministic, differential equation-based models, however there is a growing use of agent-based models. In this review, the current applications and practices of agent-based model development are reviewed via relevant case studies from the literature. Gaps in the implementation of these models are identified and a future perspective on the priorities for further agent-based model development is given.
在过去二十年里,定量数学建模方法已成为提高新药研究效率的一种范式,特别是药代动力学-药效学和定量系统药理学建模的应用。这些方法主要使用确定性的、基于微分方程的模型,但基于代理的模型的使用也越来越多。本综述通过文献中的相关案例研究,对基于代理的模型开发的当前应用和实践进行了回顾。确定了这些模型在实施过程中存在的差距,并对进一步开发基于代理的模型的优先事项提出了未来展望。
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引用次数: 0
Integrated modeling of biomarkers, survival and safety in clinical oncology drug development 临床肿瘤药物开发中的生物标记物、生存和安全性综合建模
IF 15.2 1区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2024-11-20 DOI: 10.1016/j.addr.2024.115476
Han Liu , Eman I.K. Ibrahim , Maddalena Centanni , Céline Sarr , Karthik Venkatakrishnan , Lena E. Friberg
Model-based approaches, including population pharmacokinetic-pharmacodynamic modeling, have become an essential component in the clinical phases of oncology drug development. Over the past two decades, models have evolved to describe the temporal dynamics of biomarkers and tumor size, treatment-related adverse events, and their links to survival. Integrated models, defined here as models that incorporate at least two pharmacodynamic/ outcome variables, are applied to answer drug development questions through simulations, e.g., to support the exploration of alternative dosing strategies and study designs in subgroups of patients or other tumor indications. It is expected that these pharmacometric approaches will be expanded as regulatory authorities place further emphasis on early and individualized dosage optimization and inclusive patient-focused development strategies. This review provides an overview of integrated models in the literature, examples of the considerations that need to be made when applying these advanced pharmacometric approaches, and an outlook on the expected further expansion of model-informed drug development of anticancer drugs.
基于模型的方法,包括群体药代动力学-药效学模型,已成为肿瘤药物临床开发阶段的重要组成部分。在过去二十年中,模型已经发展到可以描述生物标志物和肿瘤大小的时间动态、治疗相关不良事件及其与生存的联系。综合模型在这里被定义为包含至少两个药效学/结果变量的模型,可用于通过模拟回答药物开发问题,例如支持探索亚组患者或其他肿瘤适应症的替代剂量策略和研究设计。随着监管机构进一步强调早期和个体化剂量优化以及以患者为中心的包容性开发战略,预计这些药物计量学方法将得到扩展。本综述概述了文献中的综合模型,举例说明了应用这些先进的药物计量学方法时需要考虑的因素,并展望了以模型为依据的抗癌药物开发有望进一步扩展的前景。
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引用次数: 0
Chaotic (bio)printing in the context of drug delivery systems 药物输送系统中的混沌(生物)印刷
IF 15.2 1区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2024-11-17 DOI: 10.1016/j.addr.2024.115475
Mario Moisés Alvarez , Ariel Cantoral-Sánchez , Grissel Trujillo-de Santiago
Chaotic (bio)printing, an innovative fabrication technique that uses chaotic flows to create highly ordered microstructures within materials, may be transformative for drug delivery systems. This review explores the principles underlying chaotic flows and their application in fabricating complex, multi-material constructs designed for advanced drug delivery and controlled release. Chaotic printing enables the precise layering of different active ingredients—a feature that may greatly facilitate the development of polypills with customizable release profiles. Recently, chaos-assisted fabrication has been extended to produce micro-architected hydrogel spheres in a high-throughput manner, potentially enhancing the versatility and efficiency of drug delivery methods. In addition, chaotic bioprinting enables the creation of evolved tissue models that more accurately emulate physiological systems, providing a more relevant platform for drug testing. This review also highlights the unique advantages of chaotic printing, including the ability to fabricate tissues with organized porosity and pre-vascularized structures, addressing critical challenges in tissue engineering. Despite its promising capabilities, challenges remain, particularly in expanding the range of materials compatible with chaotic printing. Continued research and development in this area are essential to fully realize the potential of chaotic (bio)printing in advancing drug delivery, paving the way for the next generation of smart drug delivery systems and functional tissue models for drug testing.
混沌(生物)打印是一种创新的制造技术,它利用混沌流在材料中制造出高度有序的微结构,可能会改变药物输送系统。本综述探讨了混沌流动的基本原理及其在制造复杂的多材料结构中的应用,这些结构旨在实现先进的药物输送和控释。混沌打印可实现不同活性成分的精确分层--这一特性可能会极大地促进具有可定制释放特征的多丸剂的开发。此外,混沌辅助制造已被扩展到以高通量方式生产微结构水凝胶球,从而有可能提高给药方法的多样性和效率。此外,混沌生物打印技术还能创建进化的组织模型,从而更准确地模拟生理系统,为药物测试提供更相关的平台。本综述强调了混沌打印的独特优势,包括能够制造具有有组织孔隙率和预血管化结构的组织,从而解决组织工程中的关键难题。尽管混沌打印的能力前景广阔,但挑战依然存在,特别是在扩大与混沌打印兼容的材料范围方面。要充分发挥混沌(生物)打印在推进药物输送方面的潜力,为下一代智能药物输送系统和药物测试功能组织模型铺平道路,就必须在这一领域继续进行研究和开发。
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引用次数: 0
A systematic overview of strategies for photosensitizer and light delivery in antibacterial photodynamic therapy for lung infections 肺部感染抗菌光动力疗法中光敏剂和光传输策略的系统性概述
IF 15.2 1区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2024-11-15 DOI: 10.1016/j.addr.2024.115472
Margarita O. Shleeva, Galina R. Demina, Alexander P. Savitsky
Antimicrobial photodynamic therapy (aPDT) emerges as a viable treatment strategy for infections resistant to conventional antibiotics. A complex interplay of factors, including intracellular photosensitizer (PS) accumulation, photochemical reaction type, and oxygen levels, determines the efficacy of aPDT. Recent progress includes the development of modified PSs with enhanced lipophilicity and target-specific strategies to improve bacterial cell wall penetration and targeting. Nanotechnology-based approaches, such as using nanomaterials for targeted PS delivery, have shown promise in enhancing aPDT efficacy. Advancements in light delivery methods for aPDT, such as transillumination of large lesions and local light delivery using fiber optic techniques, are also being explored to optimize treatment efficacy in clinical settings. The limited number of animal models and clinical trials specifically designed to assess the efficacy of aPDT for lung infections highlights the need for further research in this critical area. The potential prospects of aPDT for lung tissue infections originating from antibiotic-resistant bacterial infections are also discussed in this review.
抗菌光动力疗法(aPDT)是治疗对传统抗生素产生抗药性的感染的一种可行方法。细胞内光敏剂(PS)积累、光化学反应类型和氧气水平等因素的复杂相互作用决定了光动力疗法的疗效。最近取得的进展包括开发了亲油性更强的改性 PS,以及改善细菌细胞壁穿透性和靶向性的靶向策略。以纳米技术为基础的方法,如使用纳米材料进行 PS 的靶向递送,已显示出提高 aPDT 疗效的前景。为了优化临床治疗效果,目前还在探索无创局部放电疗法的光传递方法,如对大面积病灶进行透射照明和使用光纤技术进行局部光传递。专门用于评估光动力治疗肺部感染疗效的动物模型和临床试验数量有限,这凸显了在这一关键领域开展进一步研究的必要性。本综述还讨论了 aPDT 治疗抗生素耐药细菌感染引起的肺组织感染的潜在前景。
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引用次数: 0
Delivery and kinetics of immersion optical clearing agents in tissues: Optical imaging from ex vivo to in vivo 浸泡式光学清除剂在组织中的输送和动力学:从体内到体外的光学成像
IF 15.2 1区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2024-10-29 DOI: 10.1016/j.addr.2024.115470
Tingting Yu , Xiang Zhong , Dongyu Li , Jingtan Zhu , Valery V. Tuchin , Dan Zhu
Advanced optical imaging provides a powerful tool for the structural and functional analysis of tissues with high resolution and contrast, but the imaging performance decreases as light propagates deeper into the tissue. Tissue optical clearing technique demonstrates an innovative way to realize deep-tissue imaging and have emerged substantially in the last two decades. Here, we briefly reviewed the basic principles of tissue optical clearing techniques in the view of delivery strategies via either free diffusion or external forces-driven advection, and the commonly-used optical techniques for monitoring kinetics of clearing agents in tissue, as well as their ex vivo to in vivo applications in multiple biomedical research fields. With future efforts on the even distribution of both clearing agents and probes, excavation of more effective clearing agents, and automation of tissue clearing processes, tissue optical clearing should provide more insights into the fundamental questions in biological events clinical diagnostics.
先进的光学成像技术为高分辨率和高对比度的组织结构和功能分析提供了强有力的工具,但成像性能会随着光线传播到组织深处而降低。组织光学清除技术是实现深部组织成像的一种创新方法,在过去二十年中得到了长足发展。在此,我们从自由扩散或外力驱动平流的传递策略角度,简要回顾了组织光学清除技术的基本原理,以及用于监测组织中清除剂动力学的常用光学技术及其在多个生物医学研究领域从体内到体外的应用。未来,随着清除剂和探针的均匀分布、更有效清除剂的挖掘以及组织清除过程的自动化,组织光学清除将为生物事件临床诊断中的基本问题提供更多见解。
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引用次数: 0
Extracellular vesicles versus lipid nanoparticles for the delivery of nucleic acids 细胞外囊泡与脂质纳米颗粒在递送核酸方面的比较
IF 15.2 1区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2024-10-28 DOI: 10.1016/j.addr.2024.115461
Johannes Bader, Finn Brigger, Jean-Christophe Leroux
Extracellular vesicles (EVs) are increasingly investigated for delivering nucleic acid (NA) therapeutics, leveraging their natural role in transporting NA and protein-based cargo in cell-to-cell signaling. Their synthetic counterparts, lipid nanoparticles (LNPs), have been developed over the past decades as NA carriers, culminating in the approval of several marketed formulations such as patisiran/Onpattro® and the mRNA-1273/BNT162 COVID-19 vaccines. The success of LNPs has sparked efforts to develop innovative technologies to target extrahepatic organs, and to deliver novel therapeutic modalities, such as tools for in vivo gene editing. Fueled by the recent advancements in both fields, this review aims to provide a comprehensive overview of the basic characteristics of EV and LNP-based NA delivery systems, from EV biogenesis to structural properties of LNPs. It addresses the primary challenges encountered in utilizing these nanocarriers from a drug formulation and delivery perspective. Additionally, biodistribution profiles, in vitro and in vivo transfection outcomes, as well as their status in clinical trials are compared. Overall, this review provides insights into promising research avenues and potential dead ends for EV and LNP-based NA delivery systems.
细胞外囊泡(EVs)在细胞间信号转导中运输核酸(NA)和基于蛋白质的货物方面发挥着天然作用,因此越来越多的研究将其用于递送核酸(NA)治疗药物。在过去的几十年里,人们开发了脂质纳米颗粒(LNPs)作为核酸载体,并最终批准了几种上市配方,如 patisiran/Onpattro® 和 mRNA-1273/BNT162 COVID-19 疫苗。LNPs 的成功促使人们努力开发针对肝外器官的创新技术,并提供新的治疗方式,如体内基因编辑工具。随着这两个领域的最新进展,本综述旨在从EV的生物发生到LNP的结构特性,全面概述EV和基于LNP的NA递送系统的基本特征。它从药物配制和递送的角度探讨了利用这些纳米载体所遇到的主要挑战。此外,还比较了生物分布特征、体外和体内转染结果以及它们在临床试验中的状况。总之,本综述为基于 EV 和 LNP 的 NA 给药系统提供了有前途的研究途径和潜在的死胡同。
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引用次数: 0
Progress of tumor-resident intracellular bacteria for cancer therapy 将肿瘤驻留细胞内细菌用于癌症治疗的进展
IF 15.2 1区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2024-10-09 DOI: 10.1016/j.addr.2024.115458
Peng Bao, Xian-Zheng Zhang
Emerging studies have disclosed the pivotal role of cancer-associated microbiota in supporting cancer development, progression and dissemination, with the in-depth comprehending of tumor microenvironment. In particular, certain invasive bacteria that hide in various cells within the tumor tissues can render assistance to tumor growth and invasion through intricate mechanisms implicated in multiple branches of cancer biology. Thus, tumor-resident intracellular microbes are anticipated as next-generation targets for oncotherapy. This review is intended to delve into these internalized bacteria-driven cancer-promoting mechanisms and explore diversified antimicrobial therapeutic strategies to counteract the detrimental impact caused by these intruders, thereby improving therapeutic benefit of antineoplastic therapy.
随着对肿瘤微环境的深入了解,新的研究揭示了癌症相关微生物群在支持癌症发展、恶化和扩散方面的关键作用。特别是,隐藏在肿瘤组织内各种细胞中的某些侵袭性细菌可通过与癌症生物学多个分支相关的复杂机制,为肿瘤的生长和侵袭提供帮助。因此,驻留在肿瘤细胞内的微生物有望成为下一代肿瘤治疗的靶点。本综述旨在深入探讨这些内化细菌驱动的促癌机制,并探索多样化的抗微生物治疗策略,以抵消这些入侵者造成的不利影响,从而提高抗肿瘤疗法的治疗效果。
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引用次数: 0
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Advanced drug delivery reviews
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