Advanced drug delivery reviews最新文献

{"title":"Implications of genetic and epigenetic aberrations to the tumorigenicity of human pluripotent stem cells","authors":"Gal Keshet ,&nbsp;Ivana Barbaric ,&nbsp;Nissim Benvenisty","doi":"10.1016/j.addr.2025.115743","DOIUrl":"10.1016/j.addr.2025.115743","url":null,"abstract":"<div><div>Human pluripotent stem cells (hPSCs) hold immense promise for cell replacement therapies due to their capacity to give rise to derivatives of the three embryonic germ layers and their ability to divide indefinitely in culture. Since their first derivation less than 30 years ago, multiple hPSC-derived cell products are already in clinical trials for a range of pathologies. Nevertheless, hPSCs also possess an intrinsic tumorigenic potential and have been shown to acquire recurrent genetic and epigenetic aberrations strongly associated with cancer initiation and progression. These properties cast doubt on the safety of hPSCs and raise concerns regarding their use for transplantation. In this review, we summarize the different kinds of genetic and epigenetic abnormalities repeatedly observed in hPSCs, how they emerge, and their potential implications for the tumorigenicity of hPSC-based products. We also discuss shared and unique abnormalities found in hPSCs derived from different sources. Finally, we suggest possible methods for reducing the occurrence of these aberrations and managing their effects once they arise.</div></div>","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":"228 ","pages":"Article 115743"},"PeriodicalIF":17.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145613732","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":"Advances in hydrogen delivery strategies for therapeutic applications","authors":"Lam-Duc-Huy Nguyen ,&nbsp;Sheng-Yao Peng ,&nbsp;Cam-Hoa Mac ,&nbsp;Nhien Nguyen ,&nbsp;Shih-Kai Lo ,&nbsp;Po-Hsi Lin ,&nbsp;Ninh-Son Pham ,&nbsp;Hsiao-Huang Chang ,&nbsp;Yu-Jung Lin ,&nbsp;Hsing-Wen Sung","doi":"10.1016/j.addr.2025.115734","DOIUrl":"10.1016/j.addr.2025.115734","url":null,"abstract":"<div><div>Molecular hydrogen (H₂) has emerged as a promising therapeutic agent owing to its selective antioxidant and anti-inflammatory properties, as well as its ability to modulate cellular signaling, metabolism, and immune responses. Beyond mitigating oxidative stress and inflammation, H₂ shows anticancer potential by altering the tumor microenvironment and inducing apoptosis. Despite encouraging findings from preclinical and clinical studies, conventional delivery routes—such as inhalation, oral intake of H₂-rich water, or injection of H₂-rich saline—face critical limitations in stability, bioavailability, and targeted delivery, impeding clinical translation. This review first outlines the therapeutic mechanisms of H₂, including redox regulation, inflammatory modulation, and tumor suppression. It then discusses current delivery approaches, their therapeutic outcomes, and inherent challenges. To overcome these barriers, a variety of advanced H₂-delivering systems have been developed, including H₂-containing carriers and <em>in situ</em> H₂-generating materials based on water-, acid-, and electrochemical reactions. Externally stimulated platforms, such as photo-, sono-, and electro-catalysis-based systems, enable spatiotemporally controlled H₂ release in response to disease-specific cues. Additionally, microbiota-targeted approaches involving probiotics and prebiotics offer indirect yet sustained H₂ delivery <em>via</em> gut fermentation. The review concludes by addressing key challenges—such as material scalability, biosafety, and integration with existing therapies—and highlights future directions for optimizing H₂ delivery through interdisciplinary innovation in materials science and medicine.</div></div>","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":"228 ","pages":"Article 115734"},"PeriodicalIF":17.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145484676","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":"Polymer-based nanomedicines: Supporting multimodal approaches to glioblastoma multiforme treatment","authors":"Amina Benaicha-Fernández ,&nbsp;Stuart P. Atkinson ,&nbsp;Inmaculada Conejos-Sánchez ,&nbsp;Maria Medel ,&nbsp;María J. Vicent","doi":"10.1016/j.addr.2025.115735","DOIUrl":"10.1016/j.addr.2025.115735","url":null,"abstract":"<div><div>Glioblastoma multiforme (GBM) remains one of the most aggressive and lethal cancers affecting the central nervous system (CNS), with significant obstacles precluding effective diagnosis, treatment, and monitoring including the presence of the blood-brain barrier, tumor heterogeneity, and an immunosuppressive tumor microenvironment. Polymer-based nanomedicines have emerged as a promising approach to overcome these barriers, offering innovative targeted diagnostic and therapeutic strategies for GBM patients. This review provides an overview of why GBM remains a diagnostic and therapeutic challenge and provides a summary of recent high-impact studies that explored how polymers and polypeptides can be employed to promote blood-brain barrier penetration and tumor accumulation and provide positive therapeutic outcomes. We also discuss the use of polymers/polypeptides in the development of multimodal therapies for GBM, including the combination of chemotherapeutic and molecularly targeted drugs/treatments, explore how they support the combination of distinct therapeutic modalities (such as phototherapy and immunotherapy) in a single platform, and describe how they apply to the development of novel GBM theranostic strategies. We then discuss the preclinical validation of polymer-based therapeutic approaches to GBM by exploring recent advances in complex in vitro and in vivo models. Finally, we look to the future of GBM treatment with nanomedicines, describing emerging therapeutic strategies for GBM and how we may boost the clinical translation of often complex polymer-based nanomedicines. Overall, this review provides robust evidence for the relevance of polymer-based nanomedicines in GBM treatment.</div></div>","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":"228 ","pages":"Article 115735"},"PeriodicalIF":17.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145546235","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":"The complex and intricate relationship between incremental science, innovation and recognition","authors":"Charlotte A. Birkmanis ,&nbsp;David W. Grainger ,&nbsp;Dietmar W. Hutmacher","doi":"10.1016/j.addr.2025.115721","DOIUrl":"10.1016/j.addr.2025.115721","url":null,"abstract":"<div><div>Science, technology, and innovation are related but distinct, leading to different research incentives. Incremental science, such as refining methods and validating findings, ensures robust results and understanding, laying the groundwork for breakthroughs. Due to pressures for ongoing innovation, fundamental research is frequently seen as an obstacle hindering scientific progress instead of an investment. The time fundamental research requires to bear fruit can detract from its immediate relevance, and impatience surrounding the urgency for rapid innovation further devalues the relatively slow, methodical approach of basic science. But this emphasis can be misleading, as many crucial advances arise from incremental improvements or refinements rather than radical breakthroughs. Insisting on scientific novelty devalues the work that lays the essential groundwork for reliable scientific progress and endorses a culture where only the most sensational achievements are celebrated, marginalising the essential contributions of those engaged in less glamorous, yet equally important, foundational research. We argue that instead of focusing on celebrating novelty and its often-unrealised societal impacts, science and technology should better value more vital basic, incremental, and knowledge-based contributions necessary for sustaining innovation and ensuring its diverse, positive impacts.</div></div>","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":"227 ","pages":"Article 115721"},"PeriodicalIF":17.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145314731","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":"Opportunities for machine learning and artificial intelligence in physiologically-based pharmacokinetic (PBPK) modeling","authors":"Anne M. Talkington ,&nbsp;Yanguang Cao ,&nbsp;Anthony J. Kearsley ,&nbsp;Samuel K. Lai","doi":"10.1016/j.addr.2025.115716","DOIUrl":"10.1016/j.addr.2025.115716","url":null,"abstract":"<div><div>Physiologically-based pharmacokinetic (PBPK) modeling is a powerful tool for quantitating and understanding the fate of drug and drug carriers in complex living systems. It is particularly valuable in situations where data are difficult to obtain due to cost, time, or ethical constraints. Recent advances in PBPK modeling have greatly improved their accuracy in modeling <em>in vivo</em> and clinical data, especially in special populations (e.g., pediatric and geriatric subjects), which consequently enhanced their utility in drug development. Nevertheless, current PBPK models remain limited by our ability to ascertain complex biological mechanisms and/or physiological processes, often resulting in many critical but unknown parameters or parameters with large uncertainty. Machine learning (ML) and applications of broader artificial intelligence (AI) tools that facilitate parameter estimation, model learning, database mining, and uncertainty quantification not only offer the potential to address the shortcomings of PBPK modeling, but also introduce opportunities for enabling earlier use of PBPK modeling in the drug development process. Here, we summarize ML-influenced advances in PBPK modeling and discuss our expectations of the likely avenues for future ML/AI contributions to PBPK modeling.</div></div>","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":"227 ","pages":"Article 115716"},"PeriodicalIF":17.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145283442","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":"Paediatric formulation challenges for enteral feeding tube administration – Current understanding and future directions","authors":"Sifan Hu ,&nbsp;Noelia Nieto González ,&nbsp;Jennifer Walsh ,&nbsp;Esmerald Hermans ,&nbsp;Giovanna Rassu ,&nbsp;Smita Salunke","doi":"10.1016/j.addr.2025.115714","DOIUrl":"10.1016/j.addr.2025.115714","url":null,"abstract":"<div><div>Enteral administration of oral dosage forms is a highly desirable treatment approach for children having impaired swallowing ability or limited gastro-intestinal access. However, the complex interplay between drug formulation and enteral feeding tube risk factors, along with the inherent anatomical and physiological differences, puts the paediatric population at a higher risk of medication administration errors via enteral feeding tubes (EFTs). Pharmaceutical companies developing drug products for the paediatric patient population are required to devise an appropriate formulation strategy and provide data to demonstrate the feasibility of administration through an EFT, yet there are limited guidelines available on evaluation of the administration of new oral paediatric drug products via EFTs. Healthcare professionals also face challenges in preparing and administering medicines through EFTs as few medications are licensed for this route of administration, and additionally, there are no harmonised guidelines on this practice. By thoroughly examining these aspects, the industry can identify specific challenges and requirements, leading to more effective and tailored drug formulations that not only meet the unique needs of paediatric patients but also ensure optimal delivery and efficacy when administered through EFTs. Moreover, a comprehensive understanding of these factors can guide regulatory evaluations and quality assurance processes. However, current literature reveals significant gaps in knowledge regarding some of these factors. There are several neglected areas that require further exploration and deeper understanding. This systematic review provides an overview of the current understanding of these factors and highlights the areas in which more targeted research is required to address the gaps, optimize formulation strategies, and the evaluations needed to demonstrate the feasibility of administration of medication via EFTs to the paediatric population. Furthermore, the understanding of these factors affecting administration of drug products through EFTs could support development of evidence-based recommendations or guidance for pharmaceutical companies to assess administration of new oral paediatric drug products via EFTs and for healthcare professionals to harmonise clinical practice.</div></div>","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":"227 ","pages":"Article 115714"},"PeriodicalIF":17.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145283692","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":"Investigating the restriction-modification barrier to DNA delivery in human gut probiotic bacteria for streamlined genetic tool development","authors":"Qiaochu Li ,&nbsp;Ibrahim Al’ Abri ,&nbsp;Nathan Crook ,&nbsp;Justin M. Vento","doi":"10.1016/j.addr.2025.115723","DOIUrl":"10.1016/j.addr.2025.115723","url":null,"abstract":"<div><div>Human gut bacteria have the potential to serve as next-generation therapeutics to many disease conditions, although poor genetic tractability limits mechanistic understanding and engineering capabilities in most strains. A major barrier to genetic tool development is bacterial defense systems such as the highly abundant restriction-modification systems that restrict DNA transformed into the cell. Although these systems are well-known barriers to DNA delivery across bacteria, their prevalence and diversity within probiotic human gut species has not been investigated. In this review, we detail the importance of DNA delivery in establishing genetic tools in bacteria and illustrate the role of restriction-modification systems in preventing DNA delivery. We then perform a computational analysis of available sequencing data to compile restriction-modification abundance and complexity in many human gut species with large probiotic potential. Through this analysis, we elucidate the large number of restriction-modification systems present in many species and highlight the diversity of restriction-modification systems in closely related strains. Among the four main types of restriction-modification systems, we pinpoint the main type(s) present in different species. To highlight strains with high potential to inhibit DNA delivery, we determine the percentage of strains from each species with multiple restriction-modification systems present. Finally, we cover established methods of bypassing the restriction-modification barrier to DNA delivery. Overall, this generalizable analysis should help others extend DNA delivery to more relevant strains across human gut bacteria to establish next generation living therapeutics from a wider range of probiotic strains.</div></div>","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":"227 ","pages":"Article 115723"},"PeriodicalIF":17.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145353351","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":"Toward pharmaceutical selective laser sintering 3D printing - a thermal and temperature-dependent analysis perspective","authors":"Marta Łaszcz ,&nbsp;Magdalena Urbanowicz ,&nbsp;Ewelina Baran ,&nbsp;Piotr Kulinowski","doi":"10.1016/j.addr.2025.115698","DOIUrl":"10.1016/j.addr.2025.115698","url":null,"abstract":"<div><div>The potential advantages of pharmaceutical additive manufacturing (AM) are thoroughly described in the literature. Challenges related to pharmaceutical AM are less discussed. Selective laser sintering (SLS) is one of the AM methods possible for pharmaceutical applications. The article addresses aspects of SLS that are not typically explored in pharmaceutical studies. The literature research was conducted in parallel for both non-pharmaceutical (technical) and pharmaceutical SLS. As a result, in-depth studies on the temperature-dependent properties (rheological and optical) and thermal properties of powders for general technical printing are presented, along with the characterization of the laser sintering process. Special attention is given to the development of the “processing window” and “energy density” terms, as they continue to evolve. An application of a wide range of thermal analysis techniques is presented, including fast differential calorimetry, hot-stage microscopy, thermovision, and dielectric thermal analysis. Next, the complexity, regarding crystalline/semicrystalline/amorphous substances combination and their melt miscibility for pharmaceutical powders is marked. Pharmaceutical SLS studies are also analyzed, with emphasis on thermal aspects. Generally, pharmaceutical studies lack meaningful temperature-dependent and thermal analysis. The only significant exception is studies on drug substance amorphization during the SLS process. The main message is that pharmaceutical SLS should benefit from the methods and ideas developed for technical SLS. In particular, the research directions should include: (1) conscious powder design regarding the specificity of SLS manufacturing method, which completely different from powder compression (API - excipients matching), (2) extending the set of research methods, (3) consolidation process elucidation, (4) powder reusing or powder reusing avoiding, (5) searching for potential new carriers/excipients dedicated to pharmaceutical SLS process.</div></div>","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":"227 ","pages":"Article 115698"},"PeriodicalIF":17.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145140546","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":"Hydrogen sulfide in cancer therapy: Intelligent delivery platforms and synergistic therapeutic paradigms","authors":"Nailin Yang ,&nbsp;Yichi Cai ,&nbsp;Shumin Sun ,&nbsp;Jihu Nie ,&nbsp;Fei Gong ,&nbsp;Zifan Pei ,&nbsp;Liang Cheng","doi":"10.1016/j.addr.2025.115717","DOIUrl":"10.1016/j.addr.2025.115717","url":null,"abstract":"<div><div>Hydrogen sulfide (H₂S) has emerged as a pivotal gaseous signaling molecule in cancer therapy, demonstrating unique dose-dependent therapeutic effects that have established new paradigms for gas-mediated treatments. To enable precise H₂S delivery in cancer therapy, various H₂S donor compounds have been developed, and a range of intelligent delivery systems have been subsequently designed. These systems are capable of specifically accumulating at tumor sites and can release H₂S in a controlled and responsive manner within the tumor microenvironment (TME). This comprehensive review systematically examines the fundamental physicochemical properties and multifaceted biological functions of H₂S while providing a detailed classification of H₂S donors into inorganic and organic categories. We further classify existing H₂S delivery strategies into endogenous-responsive systems (e.g., pH-, GSH-, and enzyme-triggered systems) and exogenous-responsive approaches (e.g., light-, ultrasound-, and electric field-activated methods), supported by representative case studies. Above all, this review highlights the remarkable potential of H₂S in enhancing various therapeutic modalities, including radiotherapy, chemotherapy, thermotherapy, catalytic therapy, and immunotherapy, primarily through its regulatory effects on heat shock protein expression, catalase activity modulation, and profound TME remodeling, which provides valuable insights for designing next-generation H₂S delivery systems and their combinatorial applications in cancer treatments.</div></div>","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":"227 ","pages":"Article 115717"},"PeriodicalIF":17.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145305861","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":"20 years of Flash NanoPrecipitation – from controlled precipitation to global medicine","authors":"Kurt D. Ristroph ,&nbsp;Nathalie M. Pinkerton ,&nbsp;Chester E. Markwalter ,&nbsp;Suzanne M. D'Addio ,&nbsp;Marian E. Gindy ,&nbsp;Robert F. Pagels","doi":"10.1016/j.addr.2025.115700","DOIUrl":"10.1016/j.addr.2025.115700","url":null,"abstract":"<div><div>In the twenty years since the development of Flash NanoPrecipitation (FNP) technology, an antisolvent precipitation technique that uses rapid turbulent mixing to drive self-assembly of polymeric or lipid nanoparticles, the platform has been used for a wide variety of drug delivery applications in research and industry – most notably as the enabling technology for the global manufacture of the Pfizer-BioNTech COMIRNATY® mRNA lipid nanoparticle vaccine against SARS-CoV-2. Importantly, this makes FNP the only publicly-known manufacturing technology for global commercial-scale lipid nanoparticle formulation. This situation makes the technique remarkable and noteworthy and worth discussing broadly, which this article aims to do. It also sets FNP mixing as the benchmark technology against which other LNP manufacturing processes should be compared. Here we review the principles underpinning this continuous antisolvent precipitation technique, its scalability and use with downstream unit operations, and its utility in nanomedicine research. We discuss the current intellectual property landscape surrounding FNP technology and give examples of its industrial implementation for SARS-CoV-2 and low-cost antimalarial formulations. We end with a survey on recent improvements and extensions to the platform that enable the encapsulation of new classes of molecules and greater flexibility in manufacturing as FNP moves into its third decade.</div></div>","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":"227 ","pages":"Article 115700"},"PeriodicalIF":17.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145203245","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}