Advanced drug delivery reviews最新文献_第4页

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

Advanced drug delivery reviews

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

Advanced drug delivery reviews

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

Advanced drug delivery reviews

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

Advanced drug delivery reviews

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。

引用次数: 0

Current status and challenges of model-informed drug discovery and development in China 中国基于模型的药物研发现状与挑战

IF 15.2 1区医学 Q1 PHARMACOLOGY & PHARMACY

Advanced drug delivery reviews

Pub Date : 2024-10-09 DOI: 10.1016/j.addr.2024.115459

Yuzhu Wang , Jia Ji , Ye Yao , Jing Nie , Fengbo Xie , Yehua Xie , Gailing Li

In the past decade, biopharmaceutical research and development in China has been notably boosted by government policies, regulatory initiatives and increasing investments in life sciences. With regulatory agency acting as a strong driver, model-informed drug development (MIDD) is transitioning rapidly from an academic pursuit to a critical component of innovative drug discovery and development within the country. In this article, we provided a cross-sectional summary on the current status of MIDD implementations across early and late-stage drug development in China, illustrated by case examples. We also shared insights into regulatory policy development and decision-making. Various modeling and simulation approaches were presented across a range of applications. Furthermore, the challenges and opportunities of MIDD in China were discussed and compared with other regions where these practices have a more established history. Through this analysis, we highlighted the potential of MIDD to enhance drug development efficiency and effectiveness in China’s evolving pharmaceutical landscape.

在过去的十年中，政府政策、监管措施以及对生命科学投资的不断增加显著推动了中国的生物制药研发。在监管机构的大力推动下，模型信息药物开发（MIDD）正从学术研究迅速转变为国内创新药物研发的重要组成部分。在这篇文章中，我们通过案例对中国药物研发早期和晚期阶段的 MIDD 实施现状进行了横向总结。我们还分享了对监管政策制定和决策的见解。我们还介绍了各种应用领域的建模和模拟方法。此外，我们还讨论了 MIDD 在中国面临的挑战和机遇，并将其与其他地区进行了比较。通过这些分析，我们强调了 MIDD 在中国不断变化的制药环境中提高药物开发效率和有效性的潜力。

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引用次数: 0

Recent applications of three-dimensional bioprinting in drug discovery and development 三维生物打印在药物研发中的最新应用。

IF 15.2 1区医学 Q1 PHARMACOLOGY & PHARMACY

Advanced drug delivery reviews

Pub Date : 2024-09-19 DOI: 10.1016/j.addr.2024.115456

Kaixing Yang , Lingxin Wang , Sanjairaj Vijayavenkataraman , Yunong Yuan , Edwin C.K. Tan , Lifeng Kang

The ability of three-dimensional (3D) bioprinting to fabricate biomimetic organ and disease models has been recognised to be promising for drug discovery and development as 3D bioprinted models can better mimic human physiology compared to two-dimensional (2D) cultures and animal models. This is useful for target selection where disease models can be studied to understand disease pathophysiology and identify disease-linked compounds. Lead identification and preclinical studies also benefit from 3D bioprinting as 3D bioprinted models can be utilised in high-throughput screening (HTS) systems and to produce efficacy and safety data that closely resembles clinical observations. Although no published applications of 3D bioprinting in clinical trials were found, there are two clinical trials planning to evaluate the predictive ability of 3D bioprinted models by comparing human and model responses to the same chemotherapy. Overall, this review provides a comprehensive summary of the latest applications of 3D bioprinting in drug discovery and development.

与二维培养物和动物模型相比，三维生物打印模型能更好地模拟人体生理学，因此三维生物打印技术制造生物仿真器官和疾病模型的能力已被公认为有望用于药物发现和开发。这对靶点选择非常有用，通过研究疾病模型可以了解疾病的病理生理学，并确定与疾病相关的化合物。由于三维生物打印模型可用于高通量筛选（HTS）系统，并能产生与临床观察结果非常相似的药效和安全性数据，因此先导鉴定和临床前研究也能从三维生物打印技术中获益。虽然没有发现三维生物打印在临床试验中的公开应用，但有两项临床试验计划通过比较人体和模型对相同化疗的反应来评估三维生物打印模型的预测能力。总之，本综述全面总结了三维生物打印在药物发现和开发中的最新应用。

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引用次数: 0

RNA-loaded nanoparticles for the treatment of hematological cancers 用于治疗血液肿瘤的 RNA 载体纳米粒子

IF 15.2 1区医学 Q1 PHARMACOLOGY & PHARMACY

Advanced drug delivery reviews

Pub Date : 2024-09-18 DOI: 10.1016/j.addr.2024.115448

Elisa Garbayo , Souhaila H. El Moukhtari , Carlos Rodríguez-Nogales , Xabier Agirre , Juan R. Rodriguez-Madoz , Paula Rodriguez-Marquez , Felipe Prósper , Patrick Couvreur , María J. Blanco-Prieto

Hematological cancers encompass a diverse group of malignancies affecting the blood, bone marrow, lymph nodes, and spleen. These disorders present unique challenges due to their complex etiology and varied clinical manifestations. Despite significant advancements in understanding and treating hematological malignancies, innovative therapeutic approaches are continually sought to enhance patient outcomes.

This review highlights the application of RNA nanoparticles (RNA-NPs) in the treatment of hematological cancers. We delve into detailed discussions on in vitro and preclinical studies involving RNA-NPs for adult patients, as well as the application of RNA-NPs in pediatric hematological cancer. The review also addresses ongoing clinical trials involving RNA-NPs and explores the emerging field of CAR-T therapy engineered by RNA-NPs. Finally, we discuss the challenges still faced in translating RNA-NP research to clinics.

血液肿瘤包括影响血液、骨髓、淋巴结和脾脏的各种恶性肿瘤。由于病因复杂、临床表现各异，这些疾病带来了独特的挑战。尽管在了解和治疗血液恶性肿瘤方面取得了重大进展，但人们仍在不断寻求创新的治疗方法来改善患者的预后。本综述重点介绍了 RNA 纳米粒子（RNA-NPs）在血液癌症治疗中的应用。我们详细讨论了针对成人患者的 RNA-NPs 体外和临床前研究，以及 RNA-NPs 在儿童血液肿瘤中的应用。综述还讨论了正在进行的涉及 RNA-NPs 的临床试验，并探讨了由 RNA-NPs 改造的 CAR-T 疗法这一新兴领域。最后，我们讨论了在将 RNA-NP 研究成果转化为临床治疗方面仍然面临的挑战。

{"title":"RNA-loaded nanoparticles for the treatment of hematological cancers","authors":"Elisa Garbayo , Souhaila H. El Moukhtari , Carlos Rodríguez-Nogales , Xabier Agirre , Juan R. Rodriguez-Madoz , Paula Rodriguez-Marquez , Felipe Prósper , Patrick Couvreur , María J. Blanco-Prieto","doi":"10.1016/j.addr.2024.115448","DOIUrl":"10.1016/j.addr.2024.115448","url":null,"abstract":"<div><p>Hematological cancers encompass a diverse group of malignancies affecting the blood, bone marrow, lymph nodes, and spleen. These disorders present unique challenges due to their complex etiology and varied clinical manifestations. Despite significant advancements in understanding and treating hematological malignancies, innovative therapeutic approaches are continually sought to enhance patient outcomes.</p><p>This review highlights the application of RNA nanoparticles (RNA-NPs) in the treatment of hematological cancers. We delve into detailed discussions on <em>in vitro</em> and preclinical studies involving RNA-NPs for adult patients, as well as the application of RNA-NPs in pediatric hematological cancer. The review also addresses ongoing clinical trials involving RNA-NPs and explores the emerging field of CAR-T therapy engineered by RNA-NPs. Finally, we discuss the challenges still faced in translating RNA-NP research to clinics.</p></div>","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":"214 ","pages":"Article 115448"},"PeriodicalIF":15.2,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0169409X24002709/pdfft?md5=394e09e402e81b0f66099b1b06ffb9f2&pid=1-s2.0-S0169409X24002709-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142271869","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Breaking the final barrier: Evolution of cationic and ionizable lipid structure in lipid nanoparticles to escape the endosome 打破最后的障碍：脂质纳米颗粒中阳离子和可电离脂质结构的演变，以逃离内质体。

IF 15.2 1区医学 Q1 PHARMACOLOGY & PHARMACY

Advanced drug delivery reviews

Pub Date : 2024-09-16 DOI: 10.1016/j.addr.2024.115446

Kaitlin Mrksich , Marshall S. Padilla , Michael J. Mitchell

In the past decade, nucleic acid therapies have seen a boon in development and clinical translation largely due to advances in nanotechnology that have enabled their safe and targeted delivery. Nanoparticles can protect nucleic acids from degradation by serum enzymes and can facilitate entry into cells. Still, achieving endosomal escape to allow nucleic acids to enter the cytoplasm has remained a significant barrier, where less than 5% of nanoparticles within the endo-lysosomal pathway are able to transfer their cargo to the cytosol. Lipid-based drug delivery vehicles, particularly lipid nanoparticles (LNPs), have been optimized to achieve potent endosomal escape, and thus have been the vector of choice in the clinic as demonstrated by their utilization in the COVID-19 mRNA vaccines. The success of LNPs is in large part due to the rational design of lipids that can specifically overcome endosomal barriers. In this review, we chart the evolution of lipid structure from cationic lipids to ionizable lipids, focusing on structure–function relationships, with a focus on how they relate to endosomal escape. Additionally, we examine recent advancements in ionizable lipid structure as well as discuss the future of lipid design.

在过去的十年中，核酸疗法在开发和临床转化方面取得了长足的进步，这主要归功于纳米技术的进步，它使核酸的安全和靶向运输成为可能。纳米颗粒可以保护核酸不被血清酶降解，并能促进核酸进入细胞。不过，实现内溶酶体逸出以允许核酸进入细胞质仍然是一个重大障碍，只有不到 5%的内溶酶体途径颗粒能够将其货物转移到细胞质中。基于脂质的药物递送载体，尤其是脂质纳米颗粒（LNPs），已经过优化，可以实现有效的内溶酶体逃逸，因此成为临床上的首选载体，COVID-19 mRNA 疫苗中的使用就证明了这一点。LNPs 的成功在很大程度上归功于能特异性突破内体屏障的脂质的合理设计。在这篇综述中，我们描绘了从阳离子脂质到可电离脂质的脂质结构演变过程，重点介绍了结构与功能的关系，尤其是与内质体逃逸的关系。此外，我们还研究了可电离脂质结构的最新进展，并讨论了脂质设计的未来。

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引用次数: 0

Application of MIDD to accelerate the development of anti-infectives: Current status and future perspectives 应用 MIDD 加速抗感染药物的开发：现状与未来展望

IF 15.2 1区医学 Q1 PHARMACOLOGY & PHARMACY

Advanced drug delivery reviews

Pub Date : 2024-09-12 DOI: 10.1016/j.addr.2024.115447

Wen Yao Mak , Qingfeng He , Wenyu Yang , Nuo Xu , Aole Zheng , Min Chen , Jiaying Lin , Yufei Shi , Xiaoqiang Xiang , Xiao Zhu

This review examines the role of model-informed drug development (MIDD) in advancing antibacterial and antiviral drug development, with an emphasis on the inclusion of host system dynamics into modeling efforts. Amidst the growing challenges of multidrug resistance and diminishing market returns, innovative methodologies are crucial for continuous drug discovery and development. The MIDD approach, with its robust capacity to integrate diverse data types, offers a promising solution. In particular, the utilization of appropriate modeling and simulation techniques for better characterization and early assessment of drug resistance are discussed. The evolution of MIDD practices across different infectious disease fields is also summarized, and compared to advancements achieved in oncology. Moving forward, the application of MIDD should expand into host system dynamics as these considerations are critical for the development of “live drugs” (e.g. chimeric antigen receptor T cells or bacteriophages) to address issues like antibiotic resistance or latent viral infections.

这篇综述探讨了模型信息药物开发（MIDD）在推进抗菌和抗病毒药物开发中的作用，重点是将宿主系统动力学纳入建模工作。在多重耐药性和市场回报日益减少的挑战下，创新方法对持续的药物发现和开发至关重要。MIDD 方法具有整合各种数据类型的强大能力，是一种很有前景的解决方案。本文特别讨论了如何利用适当的建模和模拟技术来更好地表征和早期评估耐药性。此外，还总结了 MIDD 在不同传染病领域的实践演变，并与肿瘤学领域取得的进展进行了比较。展望未来，MIDD 的应用应扩展到宿主系统动力学，因为这些考虑因素对于开发 "活药物"（如嵌合抗原受体 T 细胞或噬菌体）以解决抗生素耐药性或潜伏病毒感染等问题至关重要。

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引用次数: 0

Effects of nanoparticle deformability on multiscale biotransport 纳米粒子变形性对多尺度生物传输的影响

IF 15.2 1区医学 Q1 PHARMACOLOGY & PHARMACY

Advanced drug delivery reviews

Pub Date : 2024-08-31 DOI: 10.1016/j.addr.2024.115445

Hytham H. Gadalla , Zhongyue Yuan , Ziang Chen , Faisal Alsuwayyid , Subham Das , Harsa Mitra , Arezoo M. Ardekani , Ryan Wagner , Yoon Yeo

Deformability is one of the critical attributes of nanoparticle (NP) drug carriers, along with size, shape, and surface properties. It affects various aspects of NP biotransport, ranging from circulation and biodistribution to interactions with biological barriers and target cells. Recent studies report additional roles of NP deformability in biotransport processes, including protein corona formation, intracellular trafficking, and organelle distribution. This review focuses on the literature published in the past five years to update our understanding of NP deformability and its effect on NP biotransport. We introduce different methods of modulating and evaluating NP deformability and showcase recent studies that compare a series of NPs in their performance in biotransport events at all levels, highlighting the consensus and disagreement of the findings. It concludes with a perspective on the intricacy of systematic investigation of NP deformability and future opportunities to advance its control toward optimal drug delivery.

与尺寸、形状和表面特性一样，可变形性也是纳米粒子药物载体的关键属性之一。它影响着 NP 生物转运的各个方面，从循环和生物分布到与生物屏障和靶细胞的相互作用。最近的研究报告指出了 NP 变形性在生物转运过程中的其他作用，包括蛋白质日冕的形成、细胞内转运和细胞器分布。本综述侧重于过去五年中发表的文献，以更新我们对NP变形性及其对NP生物转运影响的认识。我们介绍了调节和评估 NP 变形性的不同方法，并展示了最近的一些研究，这些研究比较了一系列 NP 在各级生物转运事件中的表现，强调了研究结果的共识和分歧。最后，本研究透视了对 NP 变形性进行系统研究的复杂性，以及推进其控制以实现最佳药物输送的未来机遇。

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引用次数: 0