Pub Date : 2025-10-14DOI: 10.1016/j.addr.2025.115715
Amaka J. Epoh , Jailen H. Doyle , Irnela Bajrovic , Maria A. Croyle
Within the last 50 years, the emergence and re-emergence of widespread severe viral infections have caused some of the deadliest global pandemics. Thus, development of novel technologies that effectively stabilize and deliver virus-based vaccines are of high priority to public health. This review serves as a primer for those interested in developing and testing novel formulations and methods for administration of vaccines against viral infection. It starts with a brief history of immunization practices and the role they played in the evolution of vaccines available today. A brief section summarizing virus infection and immunology is provided to assist in design of studies for in vivo testing of novel vaccines. Physical properties of viruses are summarized with known physico-chemical mechanisms of virus degradation outlined. General formulation strategies to prevent degradation are discussed. Traditional and novel dosage forms for vaccine and immunization methods and up and coming technologies are also described.
{"title":"Composition, stabilization and delivery of virus-based vaccines: considerations to break free of the cold chain","authors":"Amaka J. Epoh , Jailen H. Doyle , Irnela Bajrovic , Maria A. Croyle","doi":"10.1016/j.addr.2025.115715","DOIUrl":"10.1016/j.addr.2025.115715","url":null,"abstract":"<div><div>Within the last 50 years, the emergence and re-emergence of widespread severe viral infections have caused some of the deadliest global pandemics. Thus, development of novel technologies that effectively stabilize and deliver virus-based vaccines are of high priority to public health. This review serves as a primer for those interested in developing and testing novel formulations and methods for administration of vaccines against viral infection. It starts with a brief history of immunization practices and the role they played in the evolution of vaccines available today. A brief section summarizing virus infection and immunology is provided to assist in design of studies for <em>in vivo</em> testing of novel vaccines. Physical properties of viruses are summarized with known physico-chemical mechanisms of virus degradation outlined. General formulation strategies to prevent degradation are discussed. Traditional and novel dosage forms for vaccine and immunization methods and up and coming technologies are also described.</div></div>","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":"227 ","pages":"Article 115715"},"PeriodicalIF":17.6,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145283376","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}
Pub Date : 2025-10-13DOI: 10.1016/j.addr.2025.115716
Anne M. Talkington , Yanguang Cao , Anthony J. Kearsley , Samuel K. Lai
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 in vivo 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.
{"title":"Opportunities for machine learning and artificial intelligence in physiologically-based pharmacokinetic (PBPK) modeling","authors":"Anne M. Talkington , Yanguang Cao , Anthony J. Kearsley , 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":"2025-10-13","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}
Pub Date : 2025-10-13DOI: 10.1016/j.addr.2025.115714
Sifan Hu , Noelia Nieto González , Jennifer Walsh , Esmerald Hermans , Giovanna Rassu , Smita Salunke
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.
{"title":"Paediatric formulation challenges for enteral feeding tube administration – Current understanding and future directions","authors":"Sifan Hu , Noelia Nieto González , Jennifer Walsh , Esmerald Hermans , Giovanna Rassu , 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":"2025-10-13","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}
Pub Date : 2025-10-13DOI: 10.1016/j.addr.2025.115718
Yeonju Boo , Sang-Hun Choi , Jihoon Kim , Won Jong Kim
Nitric oxide (NO) plays dual and context-dependent roles in the immune system, functioning as either an immunostimulatory or immunosuppressive mediator depending on its concentration, cellular source, and exposure dynamics. Dysregulated endogenous NO production is implicated in the pathogenesis of a broad spectrum of diseases. Therapeutic modulation of NO levels via engineered delivery systems represents a promising approach for immune regulation. This review provides a comprehensive overview of NO-modulating biomaterials, with a focus on two opposing strategies: NO scavenging to remove pathologically excessive NO and NO delivery to restore physiologically essential NO levels. We first examined the distinct molecular mechanisms and cell type-specific effects of endogenous and exogenous NO, highlighting its pleiotropic immunoregulatory roles in macrophages, dendritic cells, T cells, B cells, neutrophils, and myeloid-derived suppressor cells. We then classify representative NO scavengers and NO donors according to their chemical structures and activation triggers, including pH, redox, enzyme, and stimulus-responsive systems. Next, we discuss the design and application of advanced biomaterial-based platforms that integrate these agents into immunoengineering interventions for various disease models. Finally, we address the key translational challenges and design principles required to achieve precise, spatiotemporally controlled, and disease-selective NO modulation. Collectively, this review summarizes recent advances in NO-regulating biomaterials and highlights their potential to reprogram immune responses for therapeutic benefit.
{"title":"Nitric oxide-modulating biomaterials for therapeutic Immunoengineering","authors":"Yeonju Boo , Sang-Hun Choi , Jihoon Kim , Won Jong Kim","doi":"10.1016/j.addr.2025.115718","DOIUrl":"10.1016/j.addr.2025.115718","url":null,"abstract":"<div><div>Nitric oxide (NO) plays dual and context-dependent roles in the immune system, functioning as either an immunostimulatory or immunosuppressive mediator depending on its concentration, cellular source, and exposure dynamics. Dysregulated endogenous NO production is implicated in the pathogenesis of a broad spectrum of diseases. Therapeutic modulation of NO levels via engineered delivery systems represents a promising approach for immune regulation. This review provides a comprehensive overview of NO-modulating biomaterials, with a focus on two opposing strategies: NO scavenging to remove pathologically excessive NO and NO delivery to restore physiologically essential NO levels. We first examined the distinct molecular mechanisms and cell type-specific effects of endogenous and exogenous NO, highlighting its pleiotropic immunoregulatory roles in macrophages, dendritic cells, T cells, B cells, neutrophils, and myeloid-derived suppressor cells. We then classify representative NO scavengers and NO donors according to their chemical structures and activation triggers, including pH, redox, enzyme, and stimulus-responsive systems. Next, we discuss the design and application of advanced biomaterial-based platforms that integrate these agents into immunoengineering interventions for various disease models. Finally, we address the key translational challenges and design principles required to achieve precise, spatiotemporally controlled, and disease-selective NO modulation. Collectively, this review summarizes recent advances in NO-regulating biomaterials and highlights their potential to reprogram immune responses for therapeutic benefit.</div></div>","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":"227 ","pages":"Article 115718"},"PeriodicalIF":17.6,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145283377","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}
Pub Date : 2025-10-13DOI: 10.1016/j.addr.2025.115713
Débora Basílio-Queirós , Isabelle Rivière , Sjoukje J.C. van der Stegen , Nico Lachmann
Chimeric antigen receptor (CAR) technology has transformed the immunotherapy field with significant success in the treatment of hematological diseases. Nonetheless, challenges in scalability, donor variability as well as in the treatment of solid tumors warrants innovative solutions. Induced pluripotent stem cell (iPSC) technology has revolutionized the filed as an emerging renewable source for CAR-based therapies, facilitating the development of off-the-shelf immune cells products. This review focuses on the recent developments of iPSC-derived CAR-T cells and CAR-macrophages, including differentiation protocols, gene engineering strategies and mitigation of Graft-versus-Host Disease (GvHD), as well as alternatives for histocompatibility constraints. Additionally, we will discuss how iPSC-derivation enhances accessibility of low-frequency immune cell populations including MR1-restricted αβT, γδT, Natural Killer T (NKT) and Microglial cells. Despite great progress achieved, the limited but continuously growing clinical experience and manufacturing challenges, warrant further exploration. Advancements in manufacturing scalability and genetic engineering position iPSC-based therapies at the forefront of clinical strategies to address unmet clinical needs in cancer treatment.
{"title":"iPSC-derived T cells and macrophages: Manufacturing and next-generation application approaches","authors":"Débora Basílio-Queirós , Isabelle Rivière , Sjoukje J.C. van der Stegen , Nico Lachmann","doi":"10.1016/j.addr.2025.115713","DOIUrl":"10.1016/j.addr.2025.115713","url":null,"abstract":"<div><div>Chimeric antigen receptor (CAR) technology has transformed the immunotherapy field with significant success in the treatment of hematological diseases. Nonetheless, challenges in scalability, donor variability as well as in the treatment of solid tumors warrants innovative solutions. Induced pluripotent stem cell (iPSC) technology has revolutionized the filed as an emerging renewable source for CAR-based therapies, facilitating the development of off-the-shelf immune cells products. This review focuses on the recent developments of iPSC-derived CAR-T cells and CAR-macrophages, including differentiation protocols, gene engineering strategies and mitigation of Graft-<em>versus</em>-Host Disease (GvHD), as well as alternatives for histocompatibility constraints. Additionally, we will discuss how iPSC-derivation enhances accessibility of low-frequency immune cell populations including MR1-restricted αβT, γδT, Natural Killer T (NKT) and Microglial cells. Despite great progress achieved, the limited but continuously growing clinical experience and manufacturing challenges, warrant further exploration. Advancements in manufacturing scalability and genetic engineering position iPSC-based therapies at the forefront of clinical strategies to address unmet clinical needs in cancer treatment.</div></div>","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":"227 ","pages":"Article 115713"},"PeriodicalIF":17.6,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145283687","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}
Pub Date : 2025-10-13DOI: 10.1016/j.addr.2025.115719
Qiaoyun Li , Jaehyun Choi , Namjo Shin , Dongun Jin , Enzhen Xu , Byeongjin Ahn , Boyoung Lee , Jaiwoo Lee , Yu-Kyoung Oh
Cold atmospheric plasma (CAP) has emerged as a promising tool for in situ gas delivery due to its ability to generate reactive oxygen and nitrogen species, which play a crucial role in oxidative stress-mediated therapeutic effects. As the fourth state of matter, CAP is characterized by unique physicochemical properties and distinct generation mechanisms, which are discussed in terms of its fundamental principles and production techniques. This review covers current CAP delivery methods, highlighting their critical role in biomedical applications. The diverse therapeutic potential of CAP is explored, including its immunomodulatory effects in cancer therapy and its antimicrobial properties in wound healing through generation of reactive oxygen and nitrogen species. CAP also demonstrates efficacy in oral, inflammatory, gastrointestinal, and neurological conditions by eliminating biofilms, promoting tissue regeneration, and modulating immune and intracellular redox signaling pathways. Additionally, special emphasis is placed on the synergistic integration of CAP with advanced drug delivery systems to enhance therapeutic efficacy. Current challenges, potential limitations, and future directions for CAP-based biomedical applications are addressed. Despite its significant potential, challenges such as precise dose control, biological safety, and clinical translation remain unresolved. Future research should focus on optimizing CAP-based therapies, developing targeted delivery strategies, and conducting comprehensive clinical studies to facilitate its integration into mainstream medical practice.
{"title":"Cold atmospheric plasma for gas therapy and gas-activated drug delivery","authors":"Qiaoyun Li , Jaehyun Choi , Namjo Shin , Dongun Jin , Enzhen Xu , Byeongjin Ahn , Boyoung Lee , Jaiwoo Lee , Yu-Kyoung Oh","doi":"10.1016/j.addr.2025.115719","DOIUrl":"10.1016/j.addr.2025.115719","url":null,"abstract":"<div><div>Cold atmospheric plasma (CAP) has emerged as a promising tool for in situ gas delivery due to its ability to generate reactive oxygen and nitrogen species, which play a crucial role in oxidative stress-mediated therapeutic effects. As the fourth state of matter, CAP is characterized by unique physicochemical properties and distinct generation mechanisms, which are discussed in terms of its fundamental principles and production techniques. This review covers current CAP delivery methods, highlighting their critical role in biomedical applications. The diverse therapeutic potential of CAP is explored, including its immunomodulatory effects in cancer therapy and its antimicrobial properties in wound healing through generation of reactive oxygen and nitrogen species. CAP also demonstrates efficacy in oral, inflammatory, gastrointestinal, and neurological conditions by eliminating biofilms, promoting tissue regeneration, and modulating immune and intracellular redox signaling pathways. Additionally, special emphasis is placed on the synergistic integration of CAP with advanced drug delivery systems to enhance therapeutic efficacy. Current challenges, potential limitations, and future directions for CAP-based biomedical applications are addressed. Despite its significant potential, challenges such as precise dose control, biological safety, and clinical translation remain unresolved. Future research should focus on optimizing CAP-based therapies, developing targeted delivery strategies, and conducting comprehensive clinical studies to facilitate its integration into mainstream medical practice.</div></div>","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":"227 ","pages":"Article 115719"},"PeriodicalIF":17.6,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145283381","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}
Pub Date : 2025-10-12DOI: 10.1016/j.addr.2025.115711
Kieran Lau , Hien A. Tran , Renjian Tan , Tushar Kumeria , Asheeta A. Prasad , Richard P. Tan , Khoon S. Lim
The development of implantable drug delivery systems has played a transformative role in modern medicine through enabling more precise, localized and sustained delivery of therapeutics. This has advantages over systemic delivery routes that often provide suboptimal drug concentrations, frequent redosing requirements and off-target effects. However, one ongoing limitation of current implantable systems has been the inability to navigate the complex and dynamic biological processes. The physical architecture of implantable constructs serves as a powerful method to control the therapeutic release from a biomaterial. Additive manufacturing, or commonly 3D-printing, has emerged as one of the most versatile and widely adopted approaches used in the development of novel biomaterials with macro to nanoscale resolution, offering an efficient and cost-effective method to create highly complex geometries, hierarchical architectures to enable region-specific drug loading. Therefore, in this review, we describe and critically evaluate the implementation of 3D-printing techniques towards designing implantable drug delivery systems. Furthermore, we analyze the effectiveness of existing strategies, discussing their utility, with a particular focus on constructs that are capable of control and sustained release of multiple drugs towards therapeutic treatments and tissue engineering. Lastly, this review discusses the current challenges and the keys opportunities that remain underutilized towards the developing the next generation of implantable drug delivery systems.
{"title":"Advancements in 3D-printing strategies towards developing effective implantable drug delivery systems: Recent applications and opportunities","authors":"Kieran Lau , Hien A. Tran , Renjian Tan , Tushar Kumeria , Asheeta A. Prasad , Richard P. Tan , Khoon S. Lim","doi":"10.1016/j.addr.2025.115711","DOIUrl":"10.1016/j.addr.2025.115711","url":null,"abstract":"<div><div>The development of implantable drug delivery systems has played a transformative role in modern medicine through enabling more precise, localized and sustained delivery of therapeutics. This has advantages over systemic delivery routes that often provide suboptimal drug concentrations, frequent redosing requirements and off-target effects. However, one ongoing limitation of current implantable systems has been the inability to navigate the complex and dynamic biological processes. The physical architecture of implantable constructs serves as a powerful method to control the therapeutic release from a biomaterial. Additive manufacturing, or commonly 3D-printing, has emerged as one of the most versatile and widely adopted approaches used in the development of novel biomaterials with macro to nanoscale resolution, offering an efficient and cost-effective method to create highly complex geometries, hierarchical architectures to enable region-specific drug loading. Therefore, in this review, we describe and critically evaluate the implementation of 3D-printing techniques towards designing implantable drug delivery systems. Furthermore, we analyze the effectiveness of existing strategies, discussing their utility, with a particular focus on constructs that are capable of control and sustained release of multiple drugs towards therapeutic treatments and tissue engineering. Lastly, this review discusses the current challenges and the keys opportunities that remain underutilized towards the developing the next generation of implantable drug delivery systems.</div></div>","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":"227 ","pages":"Article 115711"},"PeriodicalIF":17.6,"publicationDate":"2025-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145282664","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}
Pub Date : 2025-10-11DOI: 10.1016/j.addr.2025.115712
A.M. van der Does , L. v. Schledorn , R. Olmer
Chronic lung diseases (CLD), including chronic obstructive pulmonary disease (COPD), pulmonary fibrosis and pulmonary hypertension, represent a significant health burden worldwide and their incidence is steadily increasing. Specifically, COPD and lung fibrosis lead to progressive tissue loss, particularly in the alveolar region, and can currently mainly be treated symptomatically, with some therapies slowing down progression. Regenerative cell therapy offers promising approaches to repair and restore permanently damaged lung tissue, focusing on different cell types such as epithelial, stromal, endothelial and pluripotent stem cells. Despite positive results in preclinical studies and initial clinical trials, large successes are lagging behind. This shows that there is still a considerable need for further research into e.g. optimal conditions, including cell sources and administration methods in humans. Challenges such as successful translation of beneficial strategies in animal models, safety risks of new strategies and the control of cell localization need to be addressed in more detail. Future research approaches should therefore support the identification of suitable cell types, the improvement of cell protection strategies and the development of predictable human models to enable the successful clinical application of regenerative cell therapy in CLD.
{"title":"Cell-based treatments of lung diseases: overview and outlook","authors":"A.M. van der Does , L. v. Schledorn , R. Olmer","doi":"10.1016/j.addr.2025.115712","DOIUrl":"10.1016/j.addr.2025.115712","url":null,"abstract":"<div><div>Chronic lung diseases (CLD), including chronic obstructive pulmonary disease (COPD), pulmonary fibrosis and pulmonary hypertension, represent a significant health burden worldwide and their incidence is steadily increasing. Specifically, COPD and lung fibrosis lead to progressive tissue loss, particularly in the alveolar region, and can currently mainly be treated symptomatically, with some therapies slowing down progression. Regenerative cell therapy offers promising approaches to repair and restore permanently damaged lung tissue, focusing on different cell types such as epithelial, stromal, endothelial and pluripotent stem cells. Despite positive results in preclinical studies and initial clinical trials, large successes are lagging behind. This shows that there is still a considerable need for further research into e.g. optimal conditions, including cell sources and administration methods in humans. Challenges such as successful translation of beneficial strategies in animal models, safety risks of new strategies and the control of cell localization need to be addressed in more detail. Future research approaches should therefore support the identification of suitable cell types, the improvement of cell protection strategies and the development of predictable human models to enable the successful clinical application of regenerative cell therapy in CLD.</div></div>","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":"227 ","pages":"Article 115712"},"PeriodicalIF":17.6,"publicationDate":"2025-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145282665","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}
Pub Date : 2025-10-03DOI: 10.1016/j.addr.2025.115701
Shaobo Yang , Mengdi Yang , Maria Jennings , Hania Timek , Amber E. Haley , Rizwan Romee , Jiahe Li
Bacteria have emerged as versatile platforms for therapeutic delivery, owing to their inherent adaptability, genetic tractability, and ability to interface with the human microbiome and immune system. This review explores the evolution of bacterial engineering for medical applications, emphasizing drug delivery strategies enabled by bacterial surface display technologies. We outline the advantages of surface display, such as enhanced localization, prolonged therapeutic activity, and reduced systemic toxicity, over conventional bacterial secretion and lysis-based delivery methods. The review details key biological mechanisms of surface display in both Gram-negative and Gram-positive bacteria, including outer membrane proteins, sortase-mediated anchoring, and spore-based systems. We also highlight emerging applications of surface-displayed cytokines, nanobodies, and immunomodulatory proteins in cancer therapy, vaccine development, microbiome engineering, and animal health. Innovative approaches combining bacterial display with conjugation systems and biosensors expand the potential of these living therapeutics for precise, responsive, and programmable interventions. Furthermore, we propose a future roadmap that leverages computational tools such as AlphaFold and in silico screening to rationally identify optimal outer membrane anchors, accelerating the design of next-generation surface display platforms. While challenges remain, including regulatory hurdles and microbial stability, continued interdisciplinary innovation with synthetic biology promises to transform engineered bacteria into clinically viable therapeutic agents. This review positions bacterial surface display as a powerful and underexplored modality for targeted drug delivery, bridging synthetic biology, immune engineering, and translational medicine.
{"title":"Repurposing the bacterial surface display technology for drug delivery","authors":"Shaobo Yang , Mengdi Yang , Maria Jennings , Hania Timek , Amber E. Haley , Rizwan Romee , Jiahe Li","doi":"10.1016/j.addr.2025.115701","DOIUrl":"10.1016/j.addr.2025.115701","url":null,"abstract":"<div><div>Bacteria have emerged as versatile platforms for therapeutic delivery, owing to their inherent adaptability, genetic tractability, and ability to interface with the human microbiome and immune system. This review explores the evolution of bacterial engineering for medical applications, emphasizing drug delivery strategies enabled by bacterial surface display technologies. We outline the advantages of surface display, such as enhanced localization, prolonged therapeutic activity, and reduced systemic toxicity, over conventional bacterial secretion and lysis-based delivery methods. The review details key biological mechanisms of surface display in both Gram-negative and Gram-positive bacteria, including outer membrane proteins, sortase-mediated anchoring, and spore-based systems. We also highlight emerging applications of surface-displayed cytokines, nanobodies, and immunomodulatory proteins in cancer therapy, vaccine development, microbiome engineering, and animal health. Innovative approaches combining bacterial display with conjugation systems and biosensors expand the potential of these living therapeutics for precise, responsive, and programmable interventions. Furthermore, we propose a future roadmap that leverages computational tools such as AlphaFold and in silico screening to rationally identify optimal outer membrane anchors, accelerating the design of next-generation surface display platforms. While challenges remain, including regulatory hurdles and microbial stability, continued interdisciplinary innovation with synthetic biology promises to transform engineered bacteria into clinically viable therapeutic agents. This review positions bacterial surface display as a powerful and underexplored modality for targeted drug delivery, bridging synthetic biology, immune engineering, and translational medicine.</div></div>","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":"227 ","pages":"Article 115701"},"PeriodicalIF":17.6,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145216059","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}
Pub Date : 2025-10-03DOI: 10.1016/j.addr.2025.115703
Tanya Chhibber , Dekker C. Deacon , Hamidreza Ghandehari , Robert L. Judson-Torres
Melanocytes are cells that produce the pigment melanin, which provides color to the skin, eyes, and hair. Dysregulation in melanocyte function, viability, or differentiation can result in melanocyte-associated disorders that can be broadly classified based on etiology as melanocyte hyperproliferation and hyperactivation, defects in melanin synthesis, inflammatory alterations in melanin production/trafficking, melanocyte destruction, and defects in melanocyte migration. While most of these disorders are of benign origin, the cosmetic implications of these conditions are associated with significant psychosocial burden and cultural stigma, having a significant impact on affected individuals. These conditions are primarily driven by changes in underlying gene expression (both at the genetic and epigenetic levels). Targeting the underlying genetic and transcriptomic changes in melanocyte-associated disorders using gene replacement (plasmid DNA, mRNA), gene knockdown (siRNA), or miRNA replacement (miRNA) presents a promising strategy for developing treatments for these conditions. The delivery of naked nucleic acid molecules is challenging, and lipid- and polymer-based particles have been widely evaluated for the successful delivery of biologically active nucleic acids to the melanocytes. This review provides an overview of melanocyte-associated pigmentary disorders and their underlying genetic factors and examines current preclinical and clinical efforts using non-viral polymeric and lipid-based delivery systems for plasmid DNA and RNA-based therapeutics.
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