Advanced drug delivery reviews最新文献

{"title":"Engineering responsive polymeric drug delivery systems via bioorthogonal and click chemistry: From molecular design to function.","authors":"Jaehak Yu, Chenfangfei Shen, Negin Nosrati Asl, Elizabeth R Gillies","doi":"10.1016/j.addr.2026.115961","DOIUrl":"https://doi.org/10.1016/j.addr.2026.115961","url":null,"abstract":"<p><p>Stimuli-responsive polymer systems have been rapidly gaining attention for the targeted release of therapeutics. Such systems often require the construction of complex, multi-functional materials. Advancements in click and bioorthogonal reactions have therefore been increasingly used to prepare these polymeric materials, both through their synthesis in the lab as well as in their assembly in vivo at the target site. Furthermore, such reactions can even be used to trigger therapeutic release. This review will cover the main bioorthogonal and click reactions used for polymeric delivery systems including copper(I)-catalyzed azide-alkyne cycloaddition, strain-promoted cycloadditions, inverse electron demand Diels-Alder reactions, imine and hydrazone formation, and reactions of thiols such as thiol-ene, thiol-yne, thiol-Michael, and disulfide exchange. It will also provide an overview of the most important stimuli used to actuate drug release including changes in pH or redox status, enzymes, and external stimuli such as heat and light. The applications of this chemistry in a range of polymeric systems including polymer-drug conjugates, nanoparticles, polyion complexes, hydrogels, and nanogels will then be discussed. Finally a perspective of the current status of the field, challenges and areas for future exploration will be presented.</p>","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":" ","pages":"115961"},"PeriodicalIF":21.0,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148885898","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}

{"title":"From conventional biologics-device combination products to advanced therapies: current state and future trends in patient-centric delivery.","authors":"Akhilesh Bhambhani, Julie Y Wei, Hairui Zhang, Catherine Shi","doi":"10.1016/j.addr.2026.115958","DOIUrl":"https://doi.org/10.1016/j.addr.2026.115958","url":null,"abstract":"<p><p>Patient-centric Biologics-Device Combination Products (BDCP) improve patient experience and compliance, while enhancing therapeutic outcomes by enabling novel routes of delivery, tackling frequent dosing and large-volume delivery requirements, and/or by simplifying administration in a healthcare setting as well as in out-patient dosing (e.g. self-administration). They also present promising solutions to overcome vaccine immunization challenges, particularly in developing nations. The BDCP opportunities, however, are often tempered by intrinsic properties of biologics (e.g. stability, viscosity etc.) and devices (e.g. design control, human factor engineering etc.) which can be further compounded by regulatory complexity across multiple jurisdictions. This comprehensive review examines the current landscape of combination product spanning across the complexities of modality (e.g. proteins, vaccines, oligonucleotide, mRNA/lipid nanoparticle (LNP) and to a limited extent cell & gene therapy) and delivery (parenteral, oral, ocular etc.) through the lens of business drivers, phase-appropriate technical development, regulatory frameworks, and patient-centric design principles. Selected case studies and commercially approved products for each modality are also presented here. Continued investments in new and improved devices such as prefilled syringes, wearable pumps, pen devices, jet devices and autoinjectors for liquid and lyophilized products highlight the recent paradigm shift for integration of delivery devices from self-administration to personalized medicine. Persistent innovation in the field, for example, has enabled device integration beyond chronic conditions such as diabetes and autoimmune diseases and prophylactic vaccination such as flu to cancer immunotherapy. Furthermore, technical, clinical and regulatory successes in achieving novel routes of delivery (e.g. oral biologics, inhaled insulin, inhaled vaccines, intradermal vaccination etc.), smart delivery systems and digital technologies have further advanced the boundaries of BDCP to not only increase market penetration but create new markets. This not only benefits patients worldwide but also paves the way for precision medicine in the future.</p>","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":" ","pages":"115958"},"PeriodicalIF":21.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148872546","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}

{"title":"Molecular design and delivery of extracellular and membrane protein degradation chimeras","authors":"Shutong Lin,Huiling Zhou,Jiayan Qiu,Yijing Dang,Longfa Kou,Zheying Zhu,Zhiai Xu,Yi Lai,Haijun Yu","doi":"10.1016/j.addr.2026.115959","DOIUrl":"https://doi.org/10.1016/j.addr.2026.115959","url":null,"abstract":"","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":"8 1","pages":"115959"},"PeriodicalIF":16.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148895699","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}

{"title":"Microfluidics in heart-on-a-Chip platforms for cardiovascular drug discovery and cardiotoxicity assessment","authors":"Caner Dikyol,Alaa Alsaafin,David F. Bodenstein,Garrett F. Beeghly,Anna Popovic,Richard Jiang,Milica Radisic","doi":"10.1016/j.addr.2026.115972","DOIUrl":"https://doi.org/10.1016/j.addr.2026.115972","url":null,"abstract":"","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":"7 1","pages":"115972"},"PeriodicalIF":16.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148893862","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}

{"title":"Engineering peptide-drug conjugates for targeted cancer therapy: design principle, theranostic imaging, and translational challenges.","authors":"Amit Kumar, Rajeev Sharma, Awesh K Yadav","doi":"10.1016/j.addr.2026.115960","DOIUrl":"10.1016/j.addr.2026.115960","url":null,"abstract":"<p><p>Peptide-drug conjugates (PDCs) are emerging as a next-generation class of targeted therapeutics designed to overcome key limitations associated with conventional chemotherapy and antibody-drug conjugates (ADCs). By integrating a tumor-homing peptide, a cleavable or stimuli-responsive linker, and a potent cytotoxic payload, PDCs offer enhanced tumor selectivity while maintaining structural simplicity and synthetic flexibility. Compared to bulky monoclonal antibody-based systems, PDCs possess significantly smaller molecular size, enabling improved tumor penetration, rapid tissue diffusion, and reduced immunogenicity. Recent advances in peptide engineering have facilitated the development of ligands targeting integrins, G protein-coupled receptors, and other tumor-overexpressed biomarkers, promoting receptor-mediated internalization and intracellular drug release. Linker chemistry plays a pivotal role in therapeutic performance, with enzyme-sensitive, redox-responsive, and pH-cleavable linkers enabling site-specific drug activation within the tumor microenvironment. Despite their promise, PDCs face challenges including rapid renal clearance, proteolytic degradation, and limited circulation half-life. Strategies such as cyclization, PEGylation, and albumin-binding modification have been explored to enhance stability and pharmacokinetics. Furthermore, emerging theranostic PDC platforms incorporate imaging moieties or radiolabels, enabling real-time visualization of tumor targeting, biodistribution, and treatment response. Such dual-functional systems facilitate biomarker-guided patient stratification and image-guided precision therapy. This review comprehensively discusses the structural design principles, delivery barriers, pharmacokinetic considerations, applications, imaging advancements, and current clinical landscape of PDCs, highlighting their advantages over ADCs and outlining future directions for precision oncology. Collectively, PDCs represent a promising and versatile platform poised to redefine targeted cytotoxic delivery in cancer therapy.</p>","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":" ","pages":"115960"},"PeriodicalIF":21.0,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148863049","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}

{"title":"Bioactive nanomedicines for multidrug-resistant colorectal cancer: Actionable mechanisms, emerging particle classes, and translational barriers.","authors":"Milad Rasouli, Fatemeh Babaei, Nadia Fallahhossein, Adeleh Divsalar","doi":"10.1016/j.addr.2026.115957","DOIUrl":"https://doi.org/10.1016/j.addr.2026.115957","url":null,"abstract":"<p><p>Multidrug resistance (MDR) in colorectal cancer (CRC) arises from interacting tumour-cell, pharmacological and microenvironmental programmes that undermine both drug activity and delivery. Chemotherapy-associated MDR is the principal focus of this review, while resistance to targeted therapy and immunotherapy is considered where it directly affects delivery design or patient selection. Bioactive compounds can modulate several resistance pathways, but their translational value is constrained by poor solubility, instability, rapid metabolism and inadequate exposure at resistant lesions. This review critically examines when nanomedicine can make such mechanistic activity pharmacologically and translationally meaningful. We link resistance biology to delivery functions, evaluate bioactive chemosensitiser candidates against human exposure, compare major nanomedicine design strategies, and assess nano-bio interactions, repeat-dose safety, manufacturing and clinical positioning. Across the evidence, three limitations recur. First, concentrations associated with chemosensitisation for curcumin, resveratrol, epigallocatechin gallate and quercetin generally exceed measured human parent-analyte exposure. Second, many resistance claims rely on parental or poorly characterised models, whereas studies combining defined resistance provenance with functional mechanism and exposure confirmation remain uncommon. Third, human studies demonstrate feasibility, tissue exposure or treatment response, but not mechanism-specific reversal of CRC MDR by a bioactive compound or bioactive nanomedicine. Progress therefore depends less on adding new particle classes than on matching a necessary formulation function to a defined resistance or spatial barrier, quantifying active exposure in the relevant compartment, validating mechanism in appropriate models, and integrating repeat-dose safety, scalable manufacturing and biomarker-guided clinical development.</p>","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":" ","pages":"115957"},"PeriodicalIF":21.0,"publicationDate":"2026-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148757296","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}

{"title":"A toolbox to optimize and scale up microfluidic production of lipid-based nanoparticles","authors":"Amr Abostait, Mahmoud Abdelkarim, Arsalan Nikdoost, Pauline Chavrier, Mourad El Hamri, Karine Andrieux, Khair Alhareth, Hagar I. Labouta","doi":"10.1016/j.addr.2026.115946","DOIUrl":"https://doi.org/10.1016/j.addr.2026.115946","url":null,"abstract":"","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":"20 1","pages":"115946"},"PeriodicalIF":16.1,"publicationDate":"2026-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148754911","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}

{"title":"A toolbox to optimize and scale up microfluidic production of lipid-based nanoparticles.","authors":"Amr Abostait, Mahmoud Abdelkarim, Arsalan Nikdoost, Pauline Chavrier, Mourad El Hamri, Karine Andrieux, Khair Alhareth, Hagar I Labouta","doi":"10.1016/j.addr.2026.115946","DOIUrl":"https://doi.org/10.1016/j.addr.2026.115946","url":null,"abstract":"<p><p>The use of nanoparticles (NPs) for delivery, particularly for nucleic acid-based therapeutics has become a central determinant of therapeutic efficacy. To ensure safety, potency, and manufacturability across drug development stages, the physicochemical properties of NPs need to be precisely controlled. Microfluidic (MF) synthesis enables great control over the NPs formation process and maintains physicochemical properties across different production scales. MF offers economic advantages for high-throughput screening of large formulation libraries, while delivering superior reproducibility and scalability to meet regulatory requirements. In this review, we map the end-to-end workflow of MF based NPs synthesis and present an integrated \"toolbox\" of technologies to optimize this process for successful drug development. We highlight advances in chip fabrication methods and the critical performance tests required to ensure robust NPs production. We then detail the underlying principles of NPs formation in MF systems and highlight emerging computational and simulation approaches to model and predict NPs assembly. Finally, we examine the incorporation of machine learning tools to establish predictive relationships between process parameters and NPs properties. We anticipate that strategic selection of MF chip design, integrated with chip fabrication technologies, simulation-based approaches, and machine learning tools, can greatly boost experimental optimization, process control, and predictability, ultimately accelerating the clinical translation of NPs-based therapies.</p>","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":" ","pages":"115946"},"PeriodicalIF":21.0,"publicationDate":"2026-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148757061","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}

{"title":"Material-centric design of organ-on-a-chip systems: Towards industrial translation and mass manufacturing.","authors":"Javier Alejandro Hernández-Castro, Felix Lussier, Lidija Malic, Matthias Geissler, Tae-Hyeong Kim, Byeong-Ui Moon, Kebin Li, Yufeng Zhao, Liviu Clime, Daniel Brassard, Keith Morton, Teodor Veres","doi":"10.1016/j.addr.2026.115945","DOIUrl":"https://doi.org/10.1016/j.addr.2026.115945","url":null,"abstract":"<p><p>Organs-on-chips (OoCs) are miniaturized devices for culturing and stimulating living cells within microscopic fluidic environments to create minimal organ surrogates. For the last decade, a diverse range of organ models were reconstructed at the micron scale to support the investigation of fundamental biological processes. By more accurately replicating the pathophysiology of human health, OoCs can serve as alternatives to conventional 2D cell culture and animal models for drug testing. However, moving from a research prototype to a commercially viable model system requires consideration of materials and manufacturing methods to simultaneously sustain high biological fidelity of organ mimicries, while enabling fabrication at scale. This review synthesizes recent advancements in that regard: We provide an overview of materials exhibiting relevant functional properties, their associated manufacturing methods, considerations of metrology and biocompatibility, and showcase representative examples of disruptive OoCs technologies currently integrated in the drug development pipeline to accelerate the discovery of safer and more effective therapeutics.</p>","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":" ","pages":"115945"},"PeriodicalIF":21.0,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148711013","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}

{"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 ,&nbsp;Diana van der Ven ,&nbsp;Miguel A. Quetzeri-Santiago ,&nbsp;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}