Pub Date : 2026-01-01Epub Date: 2025-11-22DOI: 10.1016/j.addr.2025.115742
Pooria Lesani , Iman Zare , Mansi Khetarpaul , Zufu Lu , Azadeh Ghaee , Hala Zreiqat
The emergence of nanoparticles (NPs) has profoundly revolutionized targeted drug delivery systems, overcoming numerous limitations associated with conventional therapies. Red to near-infrared (NIR) emissive carbon dots (RNCDs) have emerged as promising theranostic candidates owing to their unique combination of superior photophysical properties, including high quantum yield (QY) and photostability, and excellent biocompatibility. This review provides a comprehensive examination of the synthesis methods of RNCDs, with a particular focus on the bottom-up approach. We explore how variations in precursor selection, solvent type, heteroatom doping, and thermal conditions influence the photophysical characteristics of RNCDs. Furthermore, we have analysed strategies for drug loading, targeting mechanisms (both passive and active), and cellular uptake pathways, highlighting methodologies employed to enhance therapeutic efficacy. The review also assesses the specific applications of RNCDs in cancer therapy and microbial infection treatments, focusing on their biocompatibility, reduced systemic phototoxicity, and minimal autofluorescence interference. Lastly, we discuss controlled drug release mechanisms, including pH-responsive, redox-sensitive, and photothermal systems, that enable controlled release profiles.
{"title":"Red to near-infrared carbon dots: synthesis, cellular interactions, drug loading, and therapeutic applications","authors":"Pooria Lesani , Iman Zare , Mansi Khetarpaul , Zufu Lu , Azadeh Ghaee , Hala Zreiqat","doi":"10.1016/j.addr.2025.115742","DOIUrl":"10.1016/j.addr.2025.115742","url":null,"abstract":"<div><div>The emergence of nanoparticles (NPs) has profoundly revolutionized targeted drug delivery systems, overcoming numerous limitations associated with conventional therapies. Red to near-infrared (NIR) emissive carbon dots (RNCDs) have emerged as promising theranostic candidates owing to their unique combination of superior photophysical properties, including high quantum yield (QY) and photostability, and excellent biocompatibility. This review provides a comprehensive examination of the synthesis methods of RNCDs, with a particular focus on the bottom-up approach. We explore how variations in precursor selection, solvent type, heteroatom doping, and thermal conditions influence the photophysical characteristics of RNCDs. Furthermore, we have analysed strategies for drug loading, targeting mechanisms (both passive and active), and cellular uptake pathways, highlighting methodologies employed to enhance therapeutic efficacy. The review also assesses the specific applications of RNCDs in cancer therapy and microbial infection treatments, focusing on their biocompatibility, reduced systemic phototoxicity, and minimal autofluorescence interference. Lastly, we discuss controlled drug release mechanisms, including pH-responsive, redox-sensitive, and photothermal systems, that enable controlled release profiles.</div></div>","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":"228 ","pages":"Article 115742"},"PeriodicalIF":17.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145575436","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 : 2026-01-01Epub Date: 2025-11-22DOI: 10.1016/j.addr.2025.115741
Yu Wang , Cheng Chen , Xin Xiao , Yajing Kang , Jinhan He , Ana Beloqui , Yining Xu
Colorectal cancer (CRC) is the third most common malignancy and the second most lethal cancer worldwide and has become a significant burden on global healthcare. The primary treatments for CRC include surgery, chemotherapy, and targeted therapy. However, these approaches face several limitations, such as invasive administration, poor patient compliance, systemic toxicity, drug resistance, and recurrence. Thus, alternative therapeutic strategies to overcome these challenges are urgently needed. Oral administration represents a promising approach for CRC treatment because of its noninvasive nature, safety, ease of self-administration, and high patient compliance. Moreover, when applied in CRC treatment, oral therapies can potentially increase therapeutic efficacy and reduce systemic toxicity via local treatment. Furthermore, the unique pathophysiological features of CRC, such as the overexpression of certain receptors and dysbiosis, present valuable opportunities for the development of advanced oral therapies. This review focuses on cutting-edge oral therapies for CRC, including nanomedicine-based and bacteria-modulating strategies. These approaches show significant promise for improving therapeutic outcomes and can be combined with existing treatment modalities to improve efficacy and minimize adverse effects. Additionally, we provide critical perspectives on the challenges and future perspectives of these strategies for CRC management. This review aims to provide novel insights into the design and advancement of oral therapies, paving the way for more effective and patient-friendly CRC treatments.
{"title":"Advanced oral therapies for colorectal cancer via nanomedicine and microbiota modulation","authors":"Yu Wang , Cheng Chen , Xin Xiao , Yajing Kang , Jinhan He , Ana Beloqui , Yining Xu","doi":"10.1016/j.addr.2025.115741","DOIUrl":"10.1016/j.addr.2025.115741","url":null,"abstract":"<div><div>Colorectal cancer (CRC) is the third most common malignancy and the second most lethal cancer worldwide and has become a significant burden on global healthcare. The primary treatments for CRC include surgery, chemotherapy, and targeted therapy. However, these approaches face several limitations, such as invasive administration, poor patient compliance, systemic toxicity, drug resistance, and recurrence. Thus, alternative therapeutic strategies to overcome these challenges are urgently needed. Oral administration represents a promising approach for CRC treatment because of its noninvasive nature, safety, ease of self-administration, and high patient compliance. Moreover, when applied in CRC treatment, oral therapies can potentially increase therapeutic efficacy and reduce systemic toxicity via local treatment. Furthermore, the unique pathophysiological features of CRC, such as the overexpression of certain receptors and dysbiosis, present valuable opportunities for the development of advanced oral therapies. This review focuses on cutting-edge oral therapies for CRC, including nanomedicine-based and bacteria-modulating strategies. These approaches show significant promise for improving therapeutic outcomes and can be combined with existing treatment modalities to improve efficacy and minimize adverse effects. Additionally, we provide critical perspectives on the challenges and future perspectives of these strategies for CRC management. This review aims to provide novel insights into the design and advancement of oral therapies, paving the way for more effective and patient-friendly CRC treatments.</div></div>","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":"228 ","pages":"Article 115741"},"PeriodicalIF":17.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145567655","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 : 2026-01-01Epub Date: 2025-11-29DOI: 10.1016/j.addr.2025.115743
Gal Keshet , Ivana Barbaric , Nissim Benvenisty
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.
{"title":"Implications of genetic and epigenetic aberrations to the tumorigenicity of human pluripotent stem cells","authors":"Gal Keshet , Ivana Barbaric , 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}
Pub Date : 2026-01-01Epub Date: 2025-11-11DOI: 10.1016/j.addr.2025.115734
Lam-Duc-Huy Nguyen , Sheng-Yao Peng , Cam-Hoa Mac , Nhien Nguyen , Shih-Kai Lo , Po-Hsi Lin , Ninh-Son Pham , Hsiao-Huang Chang , Yu-Jung Lin , Hsing-Wen Sung
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 in situ 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 via 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.
{"title":"Advances in hydrogen delivery strategies for therapeutic applications","authors":"Lam-Duc-Huy Nguyen , Sheng-Yao Peng , Cam-Hoa Mac , Nhien Nguyen , Shih-Kai Lo , Po-Hsi Lin , Ninh-Son Pham , Hsiao-Huang Chang , Yu-Jung Lin , Hsing-Wen Sung","doi":"10.1016/j.addr.2025.115734","DOIUrl":"10.1016/j.addr.2025.115734","url":null,"abstract":"<div><div>Molecular hydrogen (H<sub>2</sub>) 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, H<sub>2</sub> 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 H<sub>2</sub>-rich water, or injection of H<sub>2</sub>-rich saline—face critical limitations in stability, bioavailability, and targeted delivery, impeding clinical translation. This review first outlines the therapeutic mechanisms of H<sub>2</sub>, 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 H<sub>2</sub>-delivering systems have been developed, including H<sub>2</sub>-containing carriers and <em>in situ</em> H<sub>2</sub>-generating materials based on water-, acid-, and electrochemical reactions. Externally stimulated platforms, such as photo-, sono-, and electro-catalysis-based systems, enable spatiotemporally controlled H<sub>2</sub> release in response to disease-specific cues. Additionally, microbiota-targeted approaches involving probiotics and prebiotics offer indirect yet sustained H<sub>2</sub> 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 H<sub>2</sub> 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}
Pub Date : 2026-01-01Epub Date: 2025-11-19DOI: 10.1016/j.addr.2025.115735
Amina Benaicha-Fernández , Stuart P. Atkinson , Inmaculada Conejos-Sánchez , Maria Medel , María J. Vicent
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.
{"title":"Polymer-based nanomedicines: Supporting multimodal approaches to glioblastoma multiforme treatment","authors":"Amina Benaicha-Fernández , Stuart P. Atkinson , Inmaculada Conejos-Sánchez , Maria Medel , 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}
Pub Date : 2025-12-01Epub Date: 2025-10-19DOI: 10.1016/j.addr.2025.115721
Charlotte A. Birkmanis , David W. Grainger , Dietmar W. Hutmacher
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.
{"title":"The complex and intricate relationship between incremental science, innovation and recognition","authors":"Charlotte A. Birkmanis , David W. Grainger , 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}
Pub Date : 2025-12-01Epub Date: 2025-10-21DOI: 10.1016/j.addr.2025.115723
Qiaochu Li , Ibrahim Al’ Abri , Nathan Crook , Justin M. Vento
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.
{"title":"Investigating the restriction-modification barrier to DNA delivery in human gut probiotic bacteria for streamlined genetic tool development","authors":"Qiaochu Li , Ibrahim Al’ Abri , Nathan Crook , 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}
Pub Date : 2025-12-01Epub 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":"2025-12-01","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}
Pub Date : 2025-12-01Epub 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":"2025-12-01","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}
Pub Date : 2025-12-01Epub Date: 2025-09-25DOI: 10.1016/j.addr.2025.115698
Marta Łaszcz , Magdalena Urbanowicz , Ewelina Baran , Piotr Kulinowski
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.
{"title":"Toward pharmaceutical selective laser sintering 3D printing - a thermal and temperature-dependent analysis perspective","authors":"Marta Łaszcz , Magdalena Urbanowicz , Ewelina Baran , 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}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号