Advanced drug delivery reviews最新文献

Microfluidics meets organoids: Kidney and bladder-on-Chip models for preclinical drug delivery assessment. 微流体与类器官：用于临床前给药评估的肾脏和膀胱芯片模型。

IF 17.6 1区医学

Advanced drug delivery reviews Pub Date : 2026-05-05 DOI: 10.1016/j.addr.2026.115887

C Ma, D Koh, T Nishimura, Y Takata, Y Kameda, R Negoro, N Ishiguro, M Shibuta, I Namatame, K Tetsuka, T Araoka, M Takasato, J Jang, J Yoon, R Yokokawa

{"title":"Microfluidics meets organoids: Kidney and bladder-on-Chip models for preclinical drug delivery assessment.","authors":"C Ma, D Koh, T Nishimura, Y Takata, Y Kameda, R Negoro, N Ishiguro, M Shibuta, I Namatame, K Tetsuka, T Araoka, M Takasato, J Jang, J Yoon, R Yokokawa","doi":"10.1016/j.addr.2026.115887","DOIUrl":"https://doi.org/10.1016/j.addr.2026.115887","url":null,"abstract":"<p><p>High clinical attrition rates in drug development are frequently driven by unforeseen drug-induced nephrotoxicity, a challenge exacerbated by the profound interspecies differences and limited predictivity of conventional animal models. This translational gap is further compounded by the difficulty of recapitulating the complex, multilineage architecture of the human kidney and the stratified urothelial barrier of the bladder using traditional static cultures. Human induced pluripotent stem cell (hiPSC)-derived organoids integrated into microphysiological systems (MPS) offer a transformative opportunity to overcome these hurdles by merging human-specific biological complexity with precisely controlled engineering niches. In this review, we evaluate the evolution of kidney and bladder models from foundational platforms utilizing immortalized or primary cells to hiPSC-derived organoid-integrated chips, focusing on their quantitative capability to predict renal drug disposition and intravesical delivery. We detail the strategic integration of these human-relevant parameters into industrial physiologically based pharmacokinetic (PBPK) modeling and regulatory workflows. Furthermore, we highlight emerging synergies with multi-omics, computational \"Digital Twins,\" and multidisciplinary engineering advances, including vascularization, real-time biosensing, and 3D bioprinting technologies with AI-guided automation for scalable, reproducible production. These platforms promise to transform preclinical assessment by delivering mechanistically precise, human-relevant data for de-risking therapeutics.</p>","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":" ","pages":"115887"},"PeriodicalIF":17.6,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147832191","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Corrigendum to “Role of integrated cancer nanomedicine in overcoming drug resistance” [Adv. Drug Deliv. Rev. 65 (2013) 1784–1802] “综合癌症纳米医学在克服耐药性中的作用”的勘误表[Adv. drug delivery .]Rev. 65 (2013) 1784-1802]

IF 16.1 1区医学

Advanced drug delivery reviews Pub Date : 2026-04-04 DOI: 10.1016/j.addr.2026.115860

Arun K. Iyer, Amit Singh, Srinivas Ganta, Mansoor M. Amiji

引用次数: 0

A strategic guide of techniques for biomedical and tissue engineering applications to measure mechanical properties of soft matter, eye and skin 生物医学和组织工程应用技术的战略指南，以测量软物质，眼睛和皮肤的机械特性

IF 17.6 1区医学

Advanced drug delivery reviews Pub Date : 2026-04-01 Epub Date: 2026-01-31 DOI: 10.1016/j.addr.2026.115792

Claudia Muñoz Villaescusa , Diana van der Ven , Miguel A. Quetzeri-Santiago , David Fernandez Rivas

{"title":"A strategic guide of techniques for biomedical and tissue engineering applications to measure mechanical properties of soft matter, eye and skin","authors":"Claudia Muñoz Villaescusa , Diana van der Ven , Miguel A. Quetzeri-Santiago , David Fernandez Rivas","doi":"10.1016/j.addr.2026.115792","DOIUrl":"10.1016/j.addr.2026.115792","url":null,"abstract":"<div><div>A comprehensive understanding of tissue mechanics at the microscale is critical for advancing personalised therapies, controlled drug release, and tissue engineering. Characterising the mechanical properties of complex, soft biological materials—particularly multilayered and anisotropic organs such as the skin and eye—remains a significant challenge due to their variable water content and scale-dependent behaviour. Traditional continuum models and linear material responses often fail to capture the dynamic and nonlinear nature of these tissues under physiologically relevant conditions.</div><div>This review provides a strategic overview of state-of-the-art techniques for probing the mechanical properties of soft biological tissues, with a focus on skin and ocular systems. Our focus on the skin and eye reflects their favourable barrier properties for topical drug delivery. We examine visualisation methods including optical imaging, interferometry, digital image correlation, optical coherence microscopy, and acoustic imaging. In parallel, we assess actuation mechanisms such as indentation, cavitation rheology, and flow elastography, highlighting their suitability for <em>in vivo</em> applications. Each technique is benchmarked against key operational parameters—spatial resolution, acquisition rate, invasiveness, and strain rate—relevant to drug delivery and therapeutic engineering.</div><div>By mapping the landscape of mechanical characterisation tools, this work offers a valuable resource for researchers in biomedical engineering and beyond, including fields such as physics and chemistry, where accurate dynamic analysis of soft complex materials is essential.</div></div>","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":"231 ","pages":"Article 115792"},"PeriodicalIF":17.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146095684","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Rational modification of PROTACs for tumor-selective protein degradation 合理修饰PROTACs用于肿瘤选择性蛋白降解

IF 17.6 1区医学

Advanced drug delivery reviews Pub Date : 2026-03-01 Epub Date: 2026-01-09 DOI: 10.1016/j.addr.2026.115775

Zhongliang Fu , Meichen Pan , Chunrong Yang , Hongwei Hou , Jinghong Li

{"title":"Rational modification of PROTACs for tumor-selective protein degradation","authors":"Zhongliang Fu , Meichen Pan , Chunrong Yang , Hongwei Hou , Jinghong Li","doi":"10.1016/j.addr.2026.115775","DOIUrl":"10.1016/j.addr.2026.115775","url":null,"abstract":"<div><div>Proteolysis-targeting chimeras (PROTACs) are heterobifunctional molecules that hijack the ubiquitin-proteasome system to catalytically degrade pathogenic proteins. With the ability to target “undruggable” proteins and exert sustained pharmacological effects, PROTACs hold considerable promise for cancer therapy. However, achieving tumor-selective protein degradation remains a central challenge. This review outlines the application of PROTACs in cancer treatment and systematically summarizes emerging strategies to enhance tumor specificity. These approaches leverage hallmark features of tumors, distinctive surface biomarkers and a unique tumor microenvironment (TME), and are broadly categorized into two classes: active targeting, which employs tumor-selective ligands to enrich PROTACs in malignant cells; and conditionally activated strategies, where TME cues either selectively trigger PROTAC prodrugs or induce structural transformations in nanocarriers to enhance drug accumulation at the tumor site. By elucidating these mechanisms, we aim to bridge medicinal chemistry and intelligent nanomedicine, underpinning the tumor-selective protein degradation strategies and offering perspectives on future research directions to improve the biodistribution, safety, and therapeutic efficacy of next-generation PROTACs.</div></div>","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":"230 ","pages":"Article 115775"},"PeriodicalIF":17.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145949886","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Biologics-device combinations: Enabling prolonged therapies in the posterior segment ocular disease 生物制剂-器械组合：延长后段眼病的治疗时间

IF 17.6 1区医学

Advanced drug delivery reviews Pub Date : 2026-03-01 Epub Date: 2026-01-09 DOI: 10.1016/j.addr.2026.115773

Shuqian Zhu , Jianjun Zhang , Xuling Jiang , Cheng Peng , Huiqin Liu , Feng Qian

{"title":"Biologics-device combinations: Enabling prolonged therapies in the posterior segment ocular disease","authors":"Shuqian Zhu , Jianjun Zhang , Xuling Jiang , Cheng Peng , Huiqin Liu , Feng Qian","doi":"10.1016/j.addr.2026.115773","DOIUrl":"10.1016/j.addr.2026.115773","url":null,"abstract":"<div><div>Posterior segment ocular diseases (e.g., age-related macular degeneration and diabetic retinopathy, etc.) often necessitate frequent intravitreal (IVT) injections of biologics, due to the rapid drug clearance and formidable ocular barriers. While molecular engineering strategies and high-concentration protein formulations could extend the administration intervals to a certain extent, they are confronted with critical challenges, protein aggregation, high viscosity, and limited duration. This has spurred the development of innovative biologics-device combination products, which represent a paradigm shift towards prolonged therapy. This comprehensive review examines the latest advancements of these combination platforms, including refillable implants (e.g., SUSVIMO®), encapsulated cell technology (e.g., ENCELTO™), and recombinant adeno-associated virus (rAAV) vectors (e.g., LUXTURNA®). The progress in biologics - device combination technologies has significantly reduced the frequency of ocular injections. However, substantial hurdles, such as instability caused by material-biologics interactions, potential risks during the sterilization and manufacturing processes, safety risks, and the evolving regulatory landscape, still need to be addressed. Achieving a balance between the stability of biologics and advanced device design, enhancing long-term safety, and developing responsive smart systems with real-time monitoring and feedback capabilities remain crucial for the advancement of next-generation ophthalmic therapies.</div></div>","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":"230 ","pages":"Article 115773"},"PeriodicalIF":17.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145920277","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Bioconjugates for improved delivery of oligonucleotide therapeutics to the central nervous system 用于改善向中枢神经系统递送寡核苷酸疗法的生物偶联物

IF 17.6 1区医学

Advanced drug delivery reviews Pub Date : 2026-03-01 Epub Date: 2026-01-15 DOI: 10.1016/j.addr.2026.115778

Hye Jin Lee , Yunxuan Xie , Colin F. Greineder , Peter M. Tessier

{"title":"Bioconjugates for improved delivery of oligonucleotide therapeutics to the central nervous system","authors":"Hye Jin Lee , Yunxuan Xie , Colin F. Greineder , Peter M. Tessier","doi":"10.1016/j.addr.2026.115778","DOIUrl":"10.1016/j.addr.2026.115778","url":null,"abstract":"<div><div>Oligonucleotide therapeutics, including antisense oligonucleotides (ASOs) and small interfering RNAs (siRNAs), have gained increasing attention as a novel modality for gene-targeted interventions for central nervous system (CNS) disorders, particularly in the context of rare and inherited neurological conditions. By correcting pathogenic abnormalities in gene splicing or expression, oligonucleotide therapeutics offer a combination of extreme specificity and disease-modifying or even curative effects. However, achieving robust delivery to the CNS after systemic administration remains a significant challenge due to the presence of the blood-brain barrier and the intrinsic physicochemical limitations of oligonucleotide therapeutics, such as their large molecular size, high charge, and susceptibility to enzymatic degradation. Peptide-, antibody-, and lipid-based conjugates have emerged as versatile strategies for CNS oligonucleotide delivery, offering distinct advantages in molecular recognition, tunability, biocompatibility, and structural uniformity. Here, we review emerging design principles for engineering peptide, antibody, and lipid conjugates to enhance binding affinity, target selectivity, pharmacokinetics, and pharmacodynamics of oligonucleotide therapeutics for CNS applications. We also discuss how engineered delivery platforms have the potential to improve therapeutic efficacy across a spectrum of neurological disorders, from rare hereditary syndromes to highly prevalent neurodegenerative diseases.</div></div>","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":"230 ","pages":"Article 115778"},"PeriodicalIF":17.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145993315","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Harnessing targeted protein degradation to potentiate cancer immunotherapy: from molecular mechanisms to delivery strategies 利用靶向蛋白降解增强癌症免疫治疗：从分子机制到递送策略

IF 17.6 1区医学

Advanced drug delivery reviews Pub Date : 2026-03-01 Epub Date: 2026-01-10 DOI: 10.1016/j.addr.2026.115776

Ye Liu , Ihsan Ullah , Youyong Yuan , Jun Wang

{"title":"Harnessing targeted protein degradation to potentiate cancer immunotherapy: from molecular mechanisms to delivery strategies","authors":"Ye Liu , Ihsan Ullah , Youyong Yuan , Jun Wang","doi":"10.1016/j.addr.2026.115776","DOIUrl":"10.1016/j.addr.2026.115776","url":null,"abstract":"<div><div>Cancer immunotherapy is limited by immune escape, which is driven by overexpression of immunosuppressive proteins in the tumor microenvironment (TME). Targeted Protein Degradation (TPD) technology, utilizing cellular machinery to eliminate specific proteins, offers a powerful strategy to overcome this resistance. However, the clinical translation of TPD degraders is critically hindered by formidable delivery challenges. Their inherent physicochemical properties result in poor oral bioavailability, difficulty crossing biological barriers, rapid metabolism, and insufficient tumor accumulation, preventing effective target engagement. This review focuses on the potential of TPD technology in combination with advanced drug delivery systems (DDS) to enhance cancer immunotherapy. We elaborate on how TPD reshapes the TME by degrading key immunomodulatory targets. Critically, this review provides an in-depth analysis of the major delivery bottlenecks currently limiting the efficacy of TPD degraders. Furthermore, it introduces advanced delivery strategies designed to overcome these obstacles, including nanocarriers, hydrogels, microneedles, and various stimuli-responsive delivery systems. Successfully overcoming these delivery obstacles is vital to unlocking the full therapeutic efficacy of TPD. Such progress holds promises for reprogramming immunosuppressive TME, overcoming resistance to existing immunotherapies, broadening the population of patients responsive to treatment, and ultimately delivering durable clinical benefits to more cancer patients.</div></div>","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":"230 ","pages":"Article 115776"},"PeriodicalIF":17.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145949869","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Medicinal gases for treating central nervous system injuries 用于治疗中枢神经系统损伤的医用气体

IF 17.6 1区医学

Advanced drug delivery reviews Pub Date : 2026-03-01 Epub Date: 2026-01-22 DOI: 10.1016/j.addr.2026.115782

Rebecca I. Sienel , Nikolaus Plesnila

引用次数: 0

Editorial: Novel ultrasound-based strategies for precision therapeutics and visualization 编辑：新的基于超声的精确治疗和可视化策略。

IF 17.6 1区医学

Advanced drug delivery reviews Pub Date : 2026-03-01 Epub Date: 2025-12-16 DOI: 10.1016/j.addr.2025.115763

Xinwu Cui , Xiaoyuan Chen

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Covalent chemistry in targeted protein degradation 靶向蛋白降解中的共价化学

IF 17.6 1区医学

Advanced drug delivery reviews Pub Date : 2026-03-01 Epub Date: 2026-01-12 DOI: 10.1016/j.addr.2026.115777

Jing Tan , Yuxin Liang , Shiqun Shao , Youqing Shen

{"title":"Covalent chemistry in targeted protein degradation","authors":"Jing Tan , Yuxin Liang , Shiqun Shao , Youqing Shen","doi":"10.1016/j.addr.2026.115777","DOIUrl":"10.1016/j.addr.2026.115777","url":null,"abstract":"<div><div>Targeted protein degradation (TPD) has revolutionized drug discovery by enabling the selective removal of specific proteins within and outside cells through the cell’s natural degradation pathways. While various TPD modalities have demonstrated immense promise, the integration of covalent chemistry is rapidly emerging as a crucial approach to enhance target engagement, improve selectivity, and overcome limitations associated with non-covalent interactions. This review provides a comprehensive overview of the current landscape of covalent TPD and systematically explores how covalent chemistry advances the field of TPD. We first detail the diverse covalent modification strategies, reactive amino acid residues, and electrophilic warheads employed in the design of covalent ligands. Next, we discuss methodologies for covalent ligand discovery, including ligand-first and electrophile-first approaches. Finally, we highlight specific examples of covalent degraders across different TPD modalities, emphasizing their mechanisms of action and therapeutic potential. By integrating current knowledge and future directions, this review aims to provide insights for the rational design of next-generation covalent degraders and underscore their implications for the future of drug discovery.</div></div>","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":"230 ","pages":"Article 115777"},"PeriodicalIF":17.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145956799","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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