{"title":"Fungal quorum sensing molecules as potential drugs in the treatment of chronic wounds and their delivery.","authors":"Ilker S Bayer","doi":"10.1080/17425247.2025.2452303","DOIUrl":"10.1080/17425247.2025.2452303","url":null,"abstract":"<p><strong>Introduction: </strong>Chronic non-healing wounds have emerged as a significant global healthcare challenge. Biofilm induced wound infections has been widely acknowledged. Despite the advanced understanding of biofilm formation, the existing approaches for diagnosing biofilms in wounds remain considerably suboptimal. Chemical signals produced by fungi to sense their environment, known as quorum sensing (QS) molecules are anticipated to cause revolution in non-healing wound antisepsis.</p><p><strong>Areas covered: </strong>Biofilms render chronic wounds resistant to treatment and impede tissue repair by inducing chronic inflammation. QS is a biochemical signaling pathway that involves certain secreted molecules, namely phenylethanoids, indolyl, and sesquiterpene alcohols that can significantly minimize and obliterate bacterial biofilms if properly applied and released in wound treatments.</p><p><strong>Expert opinion: </strong>QS molecules (QSMs) possess inhibitory properties that obstruct the formation of microbial biofilms and exhibit synergism with common antimicrobials. They can disrupt biofilms formed by drug-resistant microorganisms. The understanding of the current mechanisms and advancements in the utilization of QSMs within diverse drug delivery systems, and their release dynamics will be crucial in new drug design and delivery. Exploration of co-delivery of drugs alongside QS molecules, and assessing their impact on healing of chronic wounds before moving to clinical trials remain unaddressed.</p>","PeriodicalId":94004,"journal":{"name":"Expert opinion on drug delivery","volume":" ","pages":"1-20"},"PeriodicalIF":0.0,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142960463","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":"Roadmap to discovery and early development of an mRNA loaded LNP formulation for liver therapeutic genome editing.","authors":"Annette Bak, Liping Zhou, Joanna Rejman, Marianna Yanez Arteta, Gunilla Nilsson, Marianne Ashford","doi":"10.1080/17425247.2025.2452295","DOIUrl":"https://doi.org/10.1080/17425247.2025.2452295","url":null,"abstract":"<p><strong>Introduction: </strong>mRNA therapeutics were a niche area in drug development before COVIDvaccines. Now they are used in vaccine development, for non-viral therapeuticgenome editing, <i>in vivo</i> chimericantigen receptor T (CAR T) celltherapies and protein replacement. mRNAis large, charged, and easily degraded by nucleases. It cannot get into cells,escape the endosome, and be translated to a disease-modifying protein without adelivery system such as lipid nanoparticles (LNPs).</p><p><strong>Areas covered: </strong>This article covers how to design, select, and develop an LNP fortherapeutic genome editing in the liver. The roadmap is divided into selectingthe right LNP in discovery via a design, make, test, analyze cycle (DMTA). Thedesign elements are focused on the ionizable lipid in a 4-component LNP, andinsights are provided for how to set an <i>invitro</i> and <i>in vivo</i> testingstrategy. The second section focuses on transforming the LNP into a clinicaldrug product and covers formulation, analytical development and processoptimization, with brief notes on supply and regulator strategies.</p><p><strong>Expert opinion: </strong>The perspective discusses the impact thatacademic-industry collaborations can have on developing new medicine fortherapeutic genome editing in the liver. From the cited collaborations an enhancedunderstanding of intracellular trafficking, notably endosomal escape, and theinternal structure of LNPs were attained and are deemed key to designingeffective and safe LNPs. The knowledge gained will also enable additional assays and structure activity relationships, which wouldlead to the design of the next generation delivery systems for nucleic acidtherapies.</p>","PeriodicalId":94004,"journal":{"name":"Expert opinion on drug delivery","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142967626","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}
Željka Vanić, May Wenche Jøraholmen, Nataša Škalko-Basnet
{"title":"Challenges and considerations in liposomal hydrogels for the treatment of infection.","authors":"Željka Vanić, May Wenche Jøraholmen, Nataša Škalko-Basnet","doi":"10.1080/17425247.2025.2451620","DOIUrl":"https://doi.org/10.1080/17425247.2025.2451620","url":null,"abstract":"<p><strong>Introduction: </strong>Liposomal hydrogels are novel drug delivery systems that comprise preformed liposomes incorporated in hydrogels destined for mostly localized drug therapy, herewith antimicrobial therapy. The formulation benefits from versatility of liposomes as lipid-based nanocarriers that enable delivery of various antimicrobials of different lipophilicities, and secondary vehicle, hydrogel, that assures better retention time of formulation at the infection site. Especially in an era of alarming antimicrobial resistance, efficient localized antimicrobial therapy that avoids systemic exposure of antimicrobial and related side effects is crucial.</p><p><strong>Areas covered: </strong>We provide an overview of liposomal hydrogels that were developed for superior delivery of antimicrobials at different infections sites, with focus on skin and vaginal infections. The review summarizes the challenges of infection site and most common infection-causing pathogens and offers commentary on most relevant features the formulation needs to optimize to increase the therapy outcome. We discuss the impact of liposomal composition, size, and choice of polymer-forming hydrogel on antimicrobial outcome based on the literature overview and own experience in the field.</p><p><strong>Expert opinion: </strong>Liposomal hydrogels offer improved therapy outcome in localized antimicrobial therapy. By fine-tuning of liposomal as well as hydrogel properties, formulations with superior performance can be optimized targeting specific infection site.</p>","PeriodicalId":94004,"journal":{"name":"Expert opinion on drug delivery","volume":" ","pages":"1-22"},"PeriodicalIF":0.0,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142967623","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":"Self-amplifying RNA virus vectors for drug delivery.","authors":"Kenneth Lundstrom","doi":"10.1080/17425247.2024.2445675","DOIUrl":"10.1080/17425247.2024.2445675","url":null,"abstract":"<p><strong>Introduction: </strong>Viral vectors have proven useful for delivering genetic information, such as drugs and vaccines, for therapeutic and prophylactic interventions. Self-amplifying RNA viruses possess the special feature of high-level RNA amplification in the host cell cytoplasm providing high antigen production against infectious pathogens and various types of cancers, and expression of anti-tumor genes, toxic genes, and immunostimulatory genes.</p><p><strong>Areas covered: </strong>Self-amplifying RNA viral vectors have been evaluated in animal models and clinical trials for immune responses and protection against challenges with pathogenic infectious agents and tumor cells. Likewise, immune responses, tumor regression, and tumor eradication have been monitored in preclinical and clinical settings. The literature search used in the review is based on PubMed and clinical trial/biotechnology company websites up until September 2024.</p><p><strong>Expert opinion: </strong>Self-amplifying RNA viruses have elicited strong immune responses and vaccine efficacy in animal models and humans leading to the approval of the vesicular stomatitis virus-based vaccine against Ebola virus disease in both the US and Europe. Moreover, therapeutic and prophylactic efficacy has been demonstrated in animal tumor models and cancer patients. Self-amplifying RNA viruses have also been evaluated in mouse models for neurological disorders.</p>","PeriodicalId":94004,"journal":{"name":"Expert opinion on drug delivery","volume":" ","pages":"1-15"},"PeriodicalIF":0.0,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142934178","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}
Arkady S Abdurashtov, Pavel I Proshin, Gleb B Sukhorukov
{"title":"The pursuit of linear dosage in pharmacy: reservoir-based drug delivery systems from macro to micro scale.","authors":"Arkady S Abdurashtov, Pavel I Proshin, Gleb B Sukhorukov","doi":"10.1080/17425247.2024.2448026","DOIUrl":"https://doi.org/10.1080/17425247.2024.2448026","url":null,"abstract":"<p><strong>Introduction: </strong>The pursuit of linear dosage in pharmacy is essential for achieving consistent therapeutic release and enhancing patient compliance. This review provides a comprehensive summary of zero-order drug delivery systems, with a particular focus on reservoir-based systems emanated from different microfabrication technologies.</p><p><strong>Areas covered: </strong>The consideration of recent advances in drug delivery systems is given to encompass the key areas including the importance of achieving a constant drug release rate for therapeutic applications. Detailed examination of reservoir-based systems, their design, mechanisms of action and materials used are highlighted. By addressing these areas, the discussion aims to provide a thorough understanding of most recent zero-order drug delivery systems, their performance advantages and methods of their manufacturing. To ensure the complete coverage of the explored research area, modern AI-assistant tools were used to find not only the most relevant, but also connected and similar articles.</p><p><strong>Expert opinion: </strong>Future developments in reservoir-based drug delivery systems are expected to significantly enhance therapeutic effectiveness and patient outcomes through the integration of innovative materials and technologies. The fabrication of intelligent drug delivery systems that utilize sensors and feedback mechanisms can enable real-time monitoring of drug release and patient reactions.</p>","PeriodicalId":94004,"journal":{"name":"Expert opinion on drug delivery","volume":" ","pages":"1-20"},"PeriodicalIF":0.0,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142960473","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}
Ramkumar Menon, Lauren S Richardson, Ananth Kumar Kammala
{"title":"How can we advance drug delivery options using extracellular vesicles for pregnant women to reduce preterm birth?","authors":"Ramkumar Menon, Lauren S Richardson, Ananth Kumar Kammala","doi":"10.1080/17425247.2025.2449955","DOIUrl":"10.1080/17425247.2025.2449955","url":null,"abstract":"","PeriodicalId":94004,"journal":{"name":"Expert opinion on drug delivery","volume":" ","pages":"1-3"},"PeriodicalIF":0.0,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142928883","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":"Versatility of emulgel in topical drug delivery transforming its expedition from bench to bedside.","authors":"Pragati Ramesh Kumbhar, Harita Desai, Vaibhavi Meghraj Desai, Sakshi Priya, Vikas Rana, Gautam Singhvi","doi":"10.1080/17425247.2024.2439457","DOIUrl":"10.1080/17425247.2024.2439457","url":null,"abstract":"<p><strong>Introduction: </strong>Emulgel is a novel formulation that improves drug's stability and topical administration by combining emulsion and gel matrix. Its special structure improves skin penetration and prolongs the release of therapeutic molecules. Emulgel is unique in the commercial market because of its therapeutic effects, convenience of usage, and versatility in both pharmaceutical and cosmetic uses. This report focuses on how it may improve user experience and transform topical treatments.</p><p><strong>Areas covered: </strong>This review explores the commercial applicability of emulgels as a topical delivery system. Industrially applicable composition and manufacturing strategies have been discussed along with characterization techniques. The market landscape, being the most critical aspect, has been thoroughly discussed with recent case studies, clinical trials, patents, and commercial formulations. The compiled findings in this review are adapted from reputed databases like Scopus, PubMed, Web of Science, NIH, ClinicalTrials.gov, Espacenet, and recent research articles published between years 2010-2024 that discussed the applications of emulgel.</p><p><strong>Expert opinion: </strong>Emulgels have gained commercialization potential because of their efficient drug delivery and patient-friendly qualities. However, navigating regulatory complexity is important because imprecise classifications may affect market access. Sustained innovation will be essential for overcoming these obstacles and improving chances in future.</p>","PeriodicalId":94004,"journal":{"name":"Expert opinion on drug delivery","volume":" ","pages":"55-68"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142786981","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":"<i>Hif-1α</i> ablation reduces the efficiency of NeuroD1 gene-based therapy and aggravates the brain damage following ischemic stroke.","authors":"Nashwa Amin, Fei Wu, Bing-Xin Zhao, Zongjie Shi, Ahmed Abdelsadik, Abuelhassan Elshazly Younis, Irum Naz Abbasi, Javaria Sundus, Azhar Badry Hussein, Yu Geng, Marong Fang","doi":"10.1080/17425247.2024.2435458","DOIUrl":"10.1080/17425247.2024.2435458","url":null,"abstract":"<p><strong>Introduction: </strong>Hypoxia-inducible factor 1α [HIF1α] regulates gene expression, allowing the organism to respond to low oxygen levels. Meanwhile, astrocytes participate in inflammatory processes and are associated with neurotoxic chemicals that can increase stroke volume, contributing considerably to the devastating effects of a stroke.</p><p><strong>Objective: </strong>To evaluate whether <i>Hif-1α</i> ablation from the central nervous system is implicated in motor dysfunction and ischemic brain damage following stroke. Furthermore, to explore if <i>Hif-1α</i> ablation affects the therapeutic impact of NeuroD1 gene-based therapy.</p><p><strong>Methods: </strong>Endothelin-1 [ET-1] was injected to induce ischemic stroke in mice. Both wild-type and Hypoxia-inducible factor 1α conditional knockout [<i>Hif-1α</i> CKO] mice were used. The effect of <i>Hif-1α</i> ablation was assessed by the neuron numbers, astrocyte activity, vascular endothelial growth factor [VEGF] expression, and behavioral tests. Moreover, western blot, ELISA, and RNA sequencing were used. Then, we used pAAV2/9-GfaABC1D-NeuroD1-P2A-EGFP-WPRE injection to examine the impact of NeuroD1 in <i>Hif-1α</i> CKO mice following ischemic stroke.</p><p><strong>Results: </strong>We found that following stroke, motor dysfunction significantly increased in <i>Hif-1α</i> CKO mice. Furthermore, elevation of apoptosis and activation in both microglia and astrocytes were observed, consequently up-regulating neuroinflammation. Meanwhile, <i>Hif-1α</i> ablation significantly decreased the efficiency of NeuroD1 gene-based therapy.</p><p><strong>Conclusion: </strong>Our findings demonstrate that <i>Hif-1α</i> ablation from the nervous system is implicated in ischemic stroke pathogenesis mainly by increasing neuron cell death and inducing astrocytes as well as decreasing the efficiency of NeuroD1. These data support the idea that manipulating HIF-1α is a viable therapeutic for ischemic stroke.</p>","PeriodicalId":94004,"journal":{"name":"Expert opinion on drug delivery","volume":" ","pages":"121-138"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142782226","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}
Naznin Bhom, Khonzisizwe Somandi, Poornima Ramburrun, Yahya E Choonara
{"title":"Extracellular nanovesicles as neurotherapeutics for central nervous system disorders.","authors":"Naznin Bhom, Khonzisizwe Somandi, Poornima Ramburrun, Yahya E Choonara","doi":"10.1080/17425247.2024.2440099","DOIUrl":"10.1080/17425247.2024.2440099","url":null,"abstract":"<p><strong>Introduction: </strong>The blood-brain barrier (BBB) is a highly selective structure that protects the central nervous system (CNS) while hindering the delivery of many therapeutic agents. This presents a major challenge in treating neurological disorders, such as multiple sclerosis, where effective drug delivery to the brain is crucial for improving patient outcomes. Innovative strategies are urgently needed to address this limitation.</p><p><strong>Areas covered: </strong>This review explores the potential of extracellular vesicles (EVs) as innovative drug delivery systems capable of crossing the BBB. EVs are membrane-bound vesicles derived from cells, tissues, or plant materials, offering natural biocompatibility and therapeutic potential. Recent studies investigating the permeability of EVs and their mechanisms for crossing the BBB, such as transcytosis, are summarized. Special emphasis is placed on plant-derived EVs (PDEVs) due to their unique advantages in drug delivery. Challenges related to the large-scale production and therapeutic consistency of EVs are also discussed.</p><p><strong>Expert opinion: </strong>EVs, particularly PDEVs, hold significant promise as scalable and noninvasive systems for CNS drug delivery. However, critical barriers such as improving standardization techniques, manufacturing processes and addressing scalability must be overcome to facilitate clinical translation. Collaborative efforts in research and innovation will be pivotal in realizing the therapeutic potential of EVs for neurological conditions.</p>","PeriodicalId":94004,"journal":{"name":"Expert opinion on drug delivery","volume":" ","pages":"69-84"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142793057","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}
Andi Sun, Weijia Huang, Kai Jin, Mingyuan Zhong, Bohong Yu, Xin Li, Yongjun Wang, Hongzhuo Liu
{"title":"A multiple targeting rapamycin and SS31 conjugate enhances ischemic stroke therapy.","authors":"Andi Sun, Weijia Huang, Kai Jin, Mingyuan Zhong, Bohong Yu, Xin Li, Yongjun Wang, Hongzhuo Liu","doi":"10.1080/17425247.2024.2440094","DOIUrl":"10.1080/17425247.2024.2440094","url":null,"abstract":"<p><strong>Background: </strong>The identification of drugs targeting multiple pathways is essential for comprehensive protection against cerebral ischemia-reperfusion injury.</p><p><strong>Research design and methods: </strong>This study aimed to develop RS31, a multi-target cytoprotectant composed of SS31 (an oxidative stress mitigator) and rapamycin (Rapa), contributes anti-inflammatory and blood-brain barrier protection. RS31 was synthesized using click chemistry, and its ability to scavenge reactive oxygen species (ROS) and reduce inflammation was tested in H<sub>2</sub>O<sub>2</sub>-injured PC12 cells and LPS-stimulated BV2 cells. A C57BL/6 mouse model of transient middle cerebral artery occlusion/reperfusion (tMCAO/R) was established to assess the effect of RS31 on inflammatory factors in ischemic brain tissue. Finally, the potential of combining RS31 with PLGA microparticles (MPs) to further reduce brain edema was investigated.</p><p><strong>Results: </strong>RS31 effectively scavenged ROS and reduced inflammation. It showed a ~ 4-fold higher concentration in cerebral ischemic regions, significant reducing infarction and improving neurological function. RS31 also effectively reduced inflammatory factors, lowered malondialdehyde (MDA) levels, and increased superoxide dismutase (SOD) activity, showing strong efficacy in treating ischemic stroke.</p><p><strong>Conclusions: </strong>In vivo delivery of RS31 is an effective therapeutic strategy for I/R injury, providing a general framework for developing multi-targeted drugs against inflammatory diseases and excessive ROS production.</p>","PeriodicalId":94004,"journal":{"name":"Expert opinion on drug delivery","volume":" ","pages":"109-120"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142815357","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}