Victor Baba Oti, Vindya Ranasinghe, Brett P Dyer, Adi Idris, Nigel A J McMillan
{"title":"Assessment of the effectiveness of intranasal antiviral therapies in preclinical SARS-CoV-2 infection mouse models: a systematic review.","authors":"Victor Baba Oti, Vindya Ranasinghe, Brett P Dyer, Adi Idris, Nigel A J McMillan","doi":"10.1080/17425247.2025.2522250","DOIUrl":"10.1080/17425247.2025.2522250","url":null,"abstract":"<p><strong>Introduction: </strong>Intranasally (IN) administered antiviral therapies have emerged as a promising approach to combating SARS-CoV-2 respiratory tract infections. This systematic review aims to examine published preclinical animal studies that report anti-SARS-CoV-2 effects due to IN-delivered antiviral drugs between 1 December 2019 and 1 March 2025.</p><p><strong>Methods: </strong>Our analysis revealed 37 relevant studies out of 792 identified studies. Importantly, 15 out of the 36 selected studies performed prophylactic and post-exposure IN treatments in preclinical animal models.</p><p><strong>Results: </strong>Our systematic analysis revealed six classes of IN-delivered antiviral therapeutics that significantly improved in vivo survival and reduced target organ viremia with minimal side effects in mice. Antiviral interventions resulted in animal body weight recovery (28 studies), better clinical survival (15 studies) and reduced organ viral loads (infectious viral titers (14 studies) and RNA viral loads (28 studies)). Out of these, one study reported negative outcomes of IN interventions, significant weight loss (one study) and poorer mouse survival (two studies).</p><p><strong>Conclusions: </strong>Our systematic analysis revealed a moderate association between IN antiviral therapies and clinical and antiviral efficacy. Although the evidence supports the effectiveness of IN antiviral therapies in preclinical models, translation to clinical efficacy in humans remains uncertain.</p><p><strong>Prospero registration: </strong>CRD42024492039.</p>","PeriodicalId":94004,"journal":{"name":"Expert opinion on drug delivery","volume":" ","pages":"1-25"},"PeriodicalIF":0.0,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144319021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Priyanka Agarwal, Alice Epitropoulos, Ian Gaddie, Anat Galor, Paul Karpecki, Eric Schmidt
{"title":"All eyes on semifluorinated alkanes: a comprehensive review of the influence of semifluorinated alkane eyedrops on tear film stabilization and drug delivery in dry eye disease.","authors":"Priyanka Agarwal, Alice Epitropoulos, Ian Gaddie, Anat Galor, Paul Karpecki, Eric Schmidt","doi":"10.1080/17425247.2025.2522947","DOIUrl":"10.1080/17425247.2025.2522947","url":null,"abstract":"<p><strong>Introduction: </strong>Dry eye disease (DED) is a prevalent and multifactorial ocular disorder characterized by tear film instability, ocular surface inflammation, and patient discomfort, negatively impacting the quality of life. Conventional therapies have limitations due to poor drug bioavailability and patient tolerability.</p><p><strong>Areas covered: </strong>This review summarizes the application of semifluorinated alkanes (SFAs) as advanced ocular drug delivery systems, with a focus on perfluorobutylpentane (PFBP)-based cyclosporine A (CsA) eyedrops. Preclinical and clinical evidence highlighting the influence of SFAs on tear film dynamics, ocular bioavailability, and patient-reported outcomes has been discussed. The review compiles findings from preclinical and clinical studies reported in peer-reviewed journals and databases, including PubMed, USPTO, and conference abstracts up to 2024.</p><p><strong>Expert opinion: </strong>SFAs represent a paradigm shift in ocular drug delivery. The unique physicochemical properties of PFBP-based eyedrops, such as their water-free nature, excellent spreadability, and ability to stabilize tear film lipid layer address several challenges associated with conventional DED therapies. Clinical evidence demonstrates that PFBP-based CsA eyedrops (VEVYE®) have an earlier onset of action than aqueous CsA eyedrops and show a significant improvement in the clinical signs and symptoms of DED with high patient tolerability. These properties of PFBP make it an excellent vehicle for ocular delivery and management of ocular surface disorders.</p>","PeriodicalId":94004,"journal":{"name":"Expert opinion on drug delivery","volume":" ","pages":"1-16"},"PeriodicalIF":0.0,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144328216","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Harnessing the apical sodium-dependent bile acid transporter for enhanced oral delivery of peptide drugs: mechanisms, strategies, and therapeutic potential.","authors":"Han Zeng, Yiyao Li, Xiaopeng Deng, Peifu Xiao, Boyuan Liu, Yu Zhang, Tian Yin, Haibing He, Jingxin Gou, Xing Tang","doi":"10.1080/17425247.2025.2524005","DOIUrl":"10.1080/17425247.2025.2524005","url":null,"abstract":"<p><strong>Introduction: </strong>Oral administration of peptide drugs (PDs) faces significant challenges due to the harsh gastrointestinal environment and low intestinal epithelial permeability, leading to poor bioavailability. Current intestinal delivery pathways are often constrained by limited intestinal transport efficiency, which further hinders the effective delivery of PDs. The apical sodium-dependent bile acid transporter (ASBT) presents a promising target for enhancing the oral delivery of PDs. ASBT-mediated oral peptide delivery represents a transformative strategy by leveraging the transporter's high intestinal expression and active transport capacity, surpassing traditional passive/paracellular mechanisms.</p><p><strong>Areas covered: </strong>This review focuses on the emerging research on ASBT-based oral PDs delivery strategies, providing a comprehensive evaluation of the design concepts and principles that support these approaches and offering valuable insights for inspiring ASBT-based oral PDs delivery strategies to enhance bioavailability.</p><p><strong>Expert opinion: </strong>Current strategies predominantly rely on passive transport or paracellular transport, which, despite being widely used, suffer from low transport efficiency. On the other hand, active transport via other intestinal transporters is often limited by transporter abundance and capacity. In contrast, ASBT-mediated transport offers a high-capacity, efficient, and safe mechanism with sufficient transporter expression in the intestine, making it a promising alternative for oral PDs delivery.</p>","PeriodicalId":94004,"journal":{"name":"Expert opinion on drug delivery","volume":" ","pages":"1-19"},"PeriodicalIF":0.0,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144478330","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A semi-mechanistic pharmacokinetic/pharmacodynamic model for quantifying phage-antibiotic synergy against <i>Pseudomonas aeruginosa</i>.","authors":"Omar Assafiri, Qixuan Hong, Sandra Morales, Yu-Wei Lin, Hak-Kim Chan","doi":"10.1080/17425247.2025.2520963","DOIUrl":"10.1080/17425247.2025.2520963","url":null,"abstract":"<p><strong>Background: </strong>Multidrug-resistant (MDR) <i>Pseudomonas aeruginosa</i> is among the top three pathogens urgently needing new treatments. Phage therapy offers an alternative to antibiotics by auto-dosing and by targeting bacteria that are resistant to conventional antibiotics, and combining phages with antibiotics may overcome shortcomings of monotherapy.</p><p><strong>Research design and methods: </strong>We developed a novel semi-mechanistic pharmacokinetic/pharmacodynamic (PK/PD) model based on static <i>in</i> <i>vitro</i> time-kill data evaluating ciprofloxacin (CIPRO; 0-128 µg/mL) and bacteriophage PEV31 (0.01-100 MOI) individually and in combination against MDR <i>P.</i> <i>aeruginosa</i> strain FADDI-PA001. Additionally, a Shiny-based interactive application was designed to simulate and visualize the impact of varying concentrations of phage and antibiotic treatments, facilitating real-time regimen optimization.</p><p><strong>Results: </strong>Monotherapy with either CIPRO or PEV31 inhibited bacterial growth for less than 8 h before regrowth occurred; complete eradication was achieved only at high CIPRO concentrations (64 and 128 µg/mL). In combination (with CIPRO doses above 2 µg/mL), PEV31 and CIPRO acted synergistically, reducing bacterial levels below 10<sup>2</sup> CFU/mL at 24 h. The final PK/PD model which included a phage-bacteria-interaction term and implemented CIPRO's effect as a power-model successfully captured the observed time-kill-data for both monotherapy and combination therapy.</p><p><strong>Conclusions: </strong>These promising findings support further <i>in</i> <i>vivo</i> validation and mechanistic studies to advance combination therapy for MDR pathogens. Our integrated approach paves way for clinical translation.</p>","PeriodicalId":94004,"journal":{"name":"Expert opinion on drug delivery","volume":" ","pages":"1-10"},"PeriodicalIF":0.0,"publicationDate":"2025-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144328215","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bastian Beitzinger, Bastian Draphoen, Janina Hald, Markus Krämer, Tamara Rudolf, Felicitas Schmitt, Philipp Schwarz, Mika Lindén
{"title":"On the cellular selectivity of targeting peptide-nanoparticle conjugates - a nanoparticle perspective.","authors":"Bastian Beitzinger, Bastian Draphoen, Janina Hald, Markus Krämer, Tamara Rudolf, Felicitas Schmitt, Philipp Schwarz, Mika Lindén","doi":"10.1080/17425247.2025.2522245","DOIUrl":"10.1080/17425247.2025.2522245","url":null,"abstract":"<p><strong>Introduction: </strong>Peptide-targeted nanoparticles are promising drug carriers that can enhance drug efficacy at low systemic doses. However, clinical applications are compromised by off-target effects. Nanoparticle surface chemistry fine-tuning is key for solving these problems.</p><p><strong>Areas covered: </strong>The literature related to peptide-based, active targeting is reviewed, and critically discussed, with focus on the influence of surface chemistry influences on targetability. Furthermore, issues related to limited in vitro-in vivo predictivity are discussed.</p><p><strong>Expert opinion: </strong>The potential of more advanced in vitro methods for an increased in vivo prediction is discussed in combination with advanced computational approaches. Efforts toward enhancing endosomal escape are identified as key future developments, in combination with decreasing off-target effects.</p>","PeriodicalId":94004,"journal":{"name":"Expert opinion on drug delivery","volume":" ","pages":"1-14"},"PeriodicalIF":0.0,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144319022","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Recent advances in extracellular matrix-inspired nanocarriers.","authors":"Sanjna Rao, Kristi L Kiick","doi":"10.1080/17425247.2025.2519809","DOIUrl":"10.1080/17425247.2025.2519809","url":null,"abstract":"<p><strong>Introduction: </strong>ECM-inspired nanocarriers have emerged as a promising platform for drug delivery due to their unique advantages over traditional nanocarrier systems. The ECM is a complex three-dimensional network comprising proteins and polysaccharides that play a key role in maintaining tissue function and homeostasis. Recent advances in the design and synthesis of ECM-inspired nanocarriers have resulted in superior efficacy, targeting, and responsive delivery systems.</p><p><strong>Areas covered: </strong>This review covers ECM-inspired nanocarriers, focusing on their design and fabrication methods, and applications in drug delivery, tissue engineering, and regenerative medicine. Specific focus is placed on nanocarriers derived from elastin, collagen, hyaluronic acid, and their combinations, creating 'conjugate nanoparticles' published in the last 5 years. This review also discusses the benefits of mimicking ECM structure and function, the advantages of each nanoparticle type, challenges associated with large-scale synthesis, and immunogenicity.</p><p><strong>Expert opinion: </strong>ECM-inspired nanocarriers are a novel avenue for the delivery of therapeutics with recent emphasis placed on complex, responsive systems. While substantial progress has been made in the design and application of these nanocarriers in pre-clinical studies, significant challenges remain, particularly concerning immunogenicity, scalability, and the need for more robust clinical data, before these innovations can be widely translated into clinical practice.</p>","PeriodicalId":94004,"journal":{"name":"Expert opinion on drug delivery","volume":" ","pages":"1-19"},"PeriodicalIF":0.0,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12284898/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144277050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mumtaz, Devika Unnithan, Aysha Bano, Ajay Pratap Singh Chauhan, Javed Ali, Mohammad Ahmed Khan
{"title":"Targeting Alzheimer's disease pathology: influence of nano-based drug delivery systems loaded with a combination of herbal and synthetic drugs.","authors":"Mumtaz, Devika Unnithan, Aysha Bano, Ajay Pratap Singh Chauhan, Javed Ali, Mohammad Ahmed Khan","doi":"10.1080/17425247.2025.2513440","DOIUrl":"10.1080/17425247.2025.2513440","url":null,"abstract":"<p><strong>Introduction: </strong>Alzheimer's Disease (AD) is a progressive neurological disorder marked by cognitive decline and memory loss. Current treatments, including acetylcholinesterase inhibitors (AChEIs) and NMDA receptor antagonists, provide only symptomatic relief due to poor Blood Brain Barrier (BBB) permeability and side effects. The integration of synthetic and natural drug combinations with nanotechnology offers a promising strategy to enhance drug delivery, efficacy, and overall therapeutic outcomes.</p><p><strong>Areas covered: </strong>This review explores the integration of herbal and synthetic drugs in nano-based delivery systems for AD treatment. It examines co-loading efficiency, release kinetics, and synergistic therapeutic benefits of dual-drug formulations. Additionally, it discusses target-specific ligand functionalization for improved BBB penetration and neuronal targeting, alongside a comparative analysis of dual- vs. single-drug formulations and their impact on disease progression and efficacy.</p><p><strong>Expert opinion: </strong>Current treatments mainly offer early symptomatic relief but fail to target multiple neurobiological mechanisms of AD. Combining established therapies with herbal drugs can enhance efficacy and reduce side effects. Co-loading synthetic drugs and phytoconstituents in one nanoformulation can improve targeted delivery, sustained release, and minimize systemic effects for better outcomes.</p>","PeriodicalId":94004,"journal":{"name":"Expert opinion on drug delivery","volume":" ","pages":"1-16"},"PeriodicalIF":0.0,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144201242","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chloé Stoll, Anne Combedazou, Laurie Brunet-Manquat, Camélia Tabet, Cécile Frolet
{"title":"Feasibility of switching between different autoinjector designs: positive insights from formative Comparative Use Human Factors studies.","authors":"Chloé Stoll, Anne Combedazou, Laurie Brunet-Manquat, Camélia Tabet, Cécile Frolet","doi":"10.1080/17425247.2025.2514222","DOIUrl":"10.1080/17425247.2025.2514222","url":null,"abstract":"<p><strong>Background: </strong>Users may switch drug-device products when transitioning to generic versions. For autoinjectors, such switches can involve user interface differences, particularly in the activation mechanism, requiring either a push-on-skin step or button activation. It is essential to demonstrate that the use of a generic product remains safe and effective. This article provides preliminary usability data on various autoinjector designs, focusing on generic drug-device combination products.</p><p><strong>Research design and methods: </strong>Two formative Comparative Use Human Factors studies assessed the usability of a 3-step candidate generic button-activated autoinjector compared to RLD autoinjectors: study 1 compared it to a 4-step button-activated while study 2 compared it to a 2-step push-on-skin.</p><p><strong>Results: </strong>In study 1, 80% of participants (12/15) performed similarly with both devices. The error rate for the 3-step candidate generic autoinjector was 20% (3/15), compared to 13.3% (2/15) for the 4-step. In study 2, 90% of participants (10/11) performed similarly with both devices, with a 9% (1/11) error rate for the 3-step candidate generic autoinjector and 0% for the 2-step.</p><p><strong>Conclusion: </strong>These studies offer preliminary evidence supporting the feasibility of switching between different autoinjector activation mechanisms without introducing new risks. The main driver of usability results appears to be user familiarity rather than design differences.</p>","PeriodicalId":94004,"journal":{"name":"Expert opinion on drug delivery","volume":" ","pages":"1-14"},"PeriodicalIF":0.0,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144259678","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Adverse effects of intravenous LNP-mediated mRNA therapy in clinical trials: a systematic review and meta-analysis.","authors":"Wenhan Wu, Ziwei Wang","doi":"10.1080/17425247.2025.2517363","DOIUrl":"10.1080/17425247.2025.2517363","url":null,"abstract":"<p><strong>Introduction: </strong>Intravenous LNP-mediated mRNA therapy holds promise for treating various diseases, yet its safety, particularly regarding adverse events, remains a critical concern. This review systematically evaluates the adverse effects associated with this therapeutic approach.</p><p><strong>Methods: </strong>A comprehensive search of PubMed was conducted for clinical trials on intravenous LNP-mediated mRNA therapies. Data extraction focused on study design, participant demographics, and adverse events. Meta-analysis was performed to assess the incidence of treatment-emergent adverse events (TEAEs) and common manifestations. The risk of bias was assessed using the ROBINS-I tool.</p><p><strong>Results: </strong>A total of six phase 1/2 clinical trials on intravenous LNP-mediated mRNA therapies were included, with sample sizes ranging from 6 to 38 participants. The pooled incidence of TEAEs was 92.2% (95% CI: 77.7%-99.4%). Sensitivity analysis indicated that excluding one study with a single smaller dose reduced heterogeneity to 6.8%. The incidence of severe TEAEs was 9.2% (95% CI: 0%-38.1%) and showed substantial heterogeneity (I<sup>2</sup> = 89.87%), which was likely influenced by factors such as higher doses, multiple administrations, and patient-specific conditions like comorbidities.</p><p><strong>Conclusion: </strong>While low-dose, single-dose intravenous LNP-mediated mRNA therapies generally have a manageable safety profile, higher doses or repeated administrations may increase the risk of severe adverse events.</p><p><strong>Protocol registration: </strong>www.crd.york.ac.uk/prospero identifier is CRD42025643741.</p>","PeriodicalId":94004,"journal":{"name":"Expert opinion on drug delivery","volume":" ","pages":"1-9"},"PeriodicalIF":0.0,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144236280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hana Kadavil, Sandi Ali Adib, Alia Marei, Noora H Al-Qahtani, Ying Zhu, Ali A Al-Kinani, Raid G Alany, Husam M Younes
{"title":"Tyrosine kinase inhibitors and their promising role in treating diabetic retinopathy and other retinal vascular diseases: overview of their routes of administration, pharmacokinetics, formulations, and drug delivery applications.","authors":"Hana Kadavil, Sandi Ali Adib, Alia Marei, Noora H Al-Qahtani, Ying Zhu, Ali A Al-Kinani, Raid G Alany, Husam M Younes","doi":"10.1080/17425247.2025.2516668","DOIUrl":"10.1080/17425247.2025.2516668","url":null,"abstract":"<p><strong>Introduction: </strong>Tyrosine Kinase Inhibitors (TKIs) are emerging as a promising alternative to protein-based anti-vascular endothelial growth factors (anti-VEGF) in treating diabetic retinopathy (DR) and other retinal vascular diseases (RVD). TKIs exhibit broader inhibition of tyrosine kinase pathways, superior tissue penetration, and favorable pharmacokinetics and chemical stability, which may reduce the need for injection frequency. Despite those advantages, their ocular administration and clinical efficacy still face many challenges, but they also open many opportunities.</p><p><strong>Areas covered: </strong>This review evaluates current ocular drug delivery platforms for TKIs for intravitreal or suprachoroidal administration. It discusses TKIs' physicochemical properties and their relevance to their pharmacokinetics and clinical effectiveness. It also examines emerging technologies, such as nanotechnology and innovative polymer systems, that enhance bioavailability and prolong the drug release of TKIs.</p><p><strong>Expert opinion: </strong>The future of DR treatment lies in integrating TKIs with advanced drug delivery systems, tissue engineering, 3D printing, and other interdisciplinary innovations. Combining nanotechnology, biomaterials, regenerative medicine, and AI tools will enable targeted, prolonged, and stable delivery, overcoming current therapy limitations and offering safer, personalized, and more effective treatments. As research progresses, these advancements may revolutionize RVD management and provide hope to millions of patients globally.</p>","PeriodicalId":94004,"journal":{"name":"Expert opinion on drug delivery","volume":" ","pages":"1-27"},"PeriodicalIF":0.0,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144236281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}