Journal of Drug Delivery Science and Technology最新文献

{"title":"Development of an injectable, in situ formed hydrogel for controlled release of local anesthetics","authors":"Ana Ćuk,&nbsp;Sverre Arne Sande,&nbsp;Marianne Hiorth","doi":"10.1016/j.jddst.2025.107242","DOIUrl":"10.1016/j.jddst.2025.107242","url":null,"abstract":"<div><div>Injectable hydrogels are recognized as interesting delivery systems for local anesthetics. Calcium-alginate is expected to have particularly high potential due to the well-documented biocompatibility and the assumed beneficial effect on neural tissue. Formulating an injectable calcium-alginate hydrogel is complex since the phase transition and the mechanical properties may be changed by specific drug molecules. The purpose of this study was to investigate possibilities for encapsulating lidocaine, with the focus on tuning the gelling kinetics and the viscoelastic properties to achieve gelling time between 1 and 2 min followed by controlled drug release. Rheological analysis identified the [Ca²⁺]/[COO⁻] ratio as the key factor that could be manipulated to fine-tune both the gelling time and the crosslinking density. By lowering the ratio from 15 to 10, the gelling time was prolonged from 1.61 to 2.63, and from 1.57 to 2.78 min, for 1 % (w/v) and 1.5 % (w/v) alginate, respectively. In the presence of lidocaine, the gelling times were reduced, resulting in &lt;0.75–0.95 min for 1 % (w/v), and 1.02–1.68 min for 1.5 % (w/v) alginate. The accompanying decreases in storage moduli by lowering the ratio from 15 to 10 were almost 90 % in the drug-free formulations, and about 60 % in the presence of drug. Lidocaine affected the storage moduli in formulations with high ratio by reducing them by about 50 %. Despite the apparently reduced crosslinking density, the investigated gels displayed favorable mechanical properties and drug retention capacity, with about 80 % of lidocaine being released by Fickian diffusion during 8 h.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"112 ","pages":"Article 107242"},"PeriodicalIF":4.5,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144563882","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stimuli-responsive nanovesicles for spatiotemporal control of drug delivery in chronic cutaneous wounds: Bridging molecular pathobiology to translational nanomedicine","authors":"Mohammad Qutub ,&nbsp;Amol Tatode ,&nbsp;Zeenat Iqbal ,&nbsp;Ujban Md Hussain ,&nbsp;Jayshree Taksande ,&nbsp;Rahmuddin Khan ,&nbsp;Deepak Thakre ,&nbsp;Tanvi Premchandani ,&nbsp;Milind Umekar ,&nbsp;Sameer Sheikh","doi":"10.1016/j.jddst.2025.107238","DOIUrl":"10.1016/j.jddst.2025.107238","url":null,"abstract":"<div><div>Chronic skin wounds remain a challenging clinical problem due to persistent inflammation, poor blood vessel growth, and biofilm infections that impede healing. Traditional therapies often lack the precision for targeted drug delivery, limiting their effectiveness. In response, stimuli-responsive nanovesicles have emerged as a promising alternative. These carriers are engineered to release drugs in response to unique biochemical and biophysical signals in the wound environment. They react to internal cues such as acidic pH, oxidative stress, and elevated protease activity, as well as external triggers like near-infrared light or ultrasound. For example, pH-sensitive polymer matrices and oxidation-labile linkers have been developed to protect drugs and ensure precise release at the target site. Surface modifications with integrin-binding peptides and zwitterionic coatings improve cellular uptake and reduce immune detection, extending therapeutic action. Advances in preclinical evaluation now include 3D-bioprinted skin models and microfluidic organ chips that simulate real wound conditions, allowing detailed study of nanoparticle penetration and biological activity. Murine studies have further supported these findings by demonstrating reduced bacterial colonization and improved tissue regeneration via tracking the immune responses. However, challenges such as scaling up production and meeting stringent regulatory standards remain. Future integration with smart bandages and machine learning may further optimize drug release and dosing, paving the way for more effective chronic wound care.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"112 ","pages":"Article 107238"},"PeriodicalIF":4.5,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144548341","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Harnessing the power of nanotechnology and intelligent wound dressings to transform sports injury recovery and healing","authors":"Feng Wei ,&nbsp;Rong Siyu ,&nbsp;Sh Baghaei ,&nbsp;Soheil Salahshour","doi":"10.1016/j.jddst.2025.107240","DOIUrl":"10.1016/j.jddst.2025.107240","url":null,"abstract":"<div><div>As the field of sports medicine continues to evolve, the integration of nanoparticle-based technologies and intelligent wound dressings is poised to revolutionize the way athletes recover from injuries. In the coming years, we can expect to see a surge in the development of highly sophisticated, multifunctional wound care solutions tailored specifically for the unique demands of athletic populations. Advancements in smart materials, such as stimuli-responsive hydrogels and self-healing dressings, will enable precise control over the wound microenvironment, promoting accelerated tissue regeneration and minimizing the risk of complications. The incorporation of wireless sensors and real-time monitoring capabilities into these intelligent dressings will empower clinicians to make data-driven decisions, optimizing treatment strategies and ensuring timely interventions. Furthermore, the integration of novel drug delivery systems (DDS), including biodegradable nanoparticles and transdermal patches, will facilitate the targeted administration of therapeutic agents, enhancing the efficacy of wound healing while reducing systemic side effects. Innovations in gas-releasing dressings and nanoenzyme-based therapies will expand the arsenal of tools available to sports medicine professionals, addressing a wider range of wound types and complexities. As these cutting-edge technologies mature and transition into clinical practice, athletes will benefit from expedited recovery times, improved functional outcomes, and a swifter return to their respective sports. The convergence of nanotechnology, smart materials, and data-driven healthcare is poised to usher in a new era of personalized, precision-based wound care in the world of sports medicine.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"112 ","pages":"Article 107240"},"PeriodicalIF":4.5,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144606071","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel approach to pure cochleate preparation via electrostatic charge modulation","authors":"Nishtha Thakur,&nbsp;Shuddhodana,&nbsp;Zaher Judeh","doi":"10.1016/j.jddst.2025.107241","DOIUrl":"10.1016/j.jddst.2025.107241","url":null,"abstract":"<div><div>Cochleates are spiral structures formed from self-assembly between phospholipids and cations. They are promising drug delivery vehicles offering significant advantages such as drug protection, sustained release, and enhanced therapeutic efficacy. However, current preparation methods often produce cochleates along with undesired multiple intermediate structures, thus complicating their formulation to effective dosage forms. This study reports a novel approach to preparing cochleates with unprecedented purity using mixed anionic (DOPS/DMPS)˗cationic (DOTAP) liposomes in 9:1 ratio. Unlike anionic DOPS or DMPS liposomes, mixed cationic-anionic DOPS:DOTAP or DMPS:DOTAP liposomes show reduced electrostatic repulsion and lower stability, allowing efficient interaction with calcium. This interaction facilitates optimal self-assembly to less stable intermediate structures and a rapid transition to pure cochleates. Cationic DOTAP, in conjunction with Ca²⁺, facilitates lipid bilayer fusion by overcoming repulsive forces and reducing energy barriers through interaction with negatively charged DOPS/DMPS. Zeta potential, PDI and FESEM studies show the purity of cochleates is primarily determined by the electrostatic charges and stability properties of the liposomes and the intermediate structures. Pure cochleates produced from mixed anionic-cationic phospholipids using the reported process have immense potential as drug delivery vehicles in the (bio)pharmaceutical industry.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"112 ","pages":"Article 107241"},"PeriodicalIF":4.5,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144570934","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nanogram-scale screening of amorphous solid dispersion and its stability with monitoring phase transition using low-frequency Raman spectroscopy","authors":"Ryotaro Haku ,&nbsp;Naoto Suzuki ,&nbsp;Kento Ohashi ,&nbsp;Varin Titapiwatanakun ,&nbsp;Toshiro Fukami","doi":"10.1016/j.jddst.2025.107237","DOIUrl":"10.1016/j.jddst.2025.107237","url":null,"abstract":"<div><div>In designing of amorphous solid dispersion (ASD) which improves the solubility and absorption of poorly soluble drugs, selecting an optimal polymer to stabilize the amorphous drug is essential for developing high-quality ASDs. However, the amount of drugs available in the early stages of development is limited to a small amount, so efficient polymer selection is essential. This work aims to investigate the utility of the nano-spot method combined with low-frequency (LF) Raman spectroscopy in polymer selection to design ASDs consisting of carbamazepine (CBZ). First, LF Raman could detect changes in the crystal forms of CBZ prepared by the nano-spot method in response to a temperature increase and humidification. Subsequently, ASDs consisting of CBZ and five different polymers prepared by natural drying or freeze drying of nano-sized droplets were evaluated using LF Raman and polarized microscopy to detect the crystallization and the changes in the crystal form of CBZ. Moreover, the relative physical stability of these ASDs was compared from its crystallization behavior. As a result, the order of relative physical stability of ASDs differed depending on the manufacturing method. From these results, we have successfully detected crystallized CBZ and their crystal form changes in ASDs prepared using minimal amounts with LF Raman measurement. In conclusion, monitoring crystal transitions in samples prepared by the nano-spot method with LF Raman spectroscopy can be a helpful tool for rapid assessment of potential polymorphic changes and drug stability in the early stages of drug development of ASDs.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"112 ","pages":"Article 107237"},"PeriodicalIF":4.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144613777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Implementation of design of experiments in liposome manufacturing: ethanol injection and extrusion as a case study","authors":"Mariana Biscaia-Caleiras ,&nbsp;Joana Fiteiro ,&nbsp;Diana Lopes ,&nbsp;Tiago Fidalgo ,&nbsp;Ana Sofia Lourenço ,&nbsp;João Nuno Moreira ,&nbsp;Sérgio Simões","doi":"10.1016/j.jddst.2025.107236","DOIUrl":"10.1016/j.jddst.2025.107236","url":null,"abstract":"<div><div>Although substantial advancements in microfluidics and continuous manufacturing have been made, particularly for lipid nanoparticles (LNPs) used in nucleic acid delivery, conventional liposomes for small-molecule drugs pose distinct challenges. These formulations are typically manufactured via ethanol injection followed by extrusion, a two-step process unlike the integrated nature of microfluidics. This separation introduces additional complexity, as individual unit operations may influence each other, making early-stage optimization more difficult and often requiring iterative refinement across the process. Scaling up these conventional methods remains a challenge, especially in achieving reproducibility, scalability, and regulatory compliance.</div><div>Design of Experiments (DoE) provides a valuable framework for understanding and optimizing such processes. However, in the early development stages, particularly in industry, its use is often limited by high material costs, time-consuming analyses, and the need for timely decision-making. Moreover, the existing literature rarely offers detailed, practical guidance tailored to formulation scientists working under these constraints.</div><div>This study presents an objective, step-by-step application of DoE to early-phase liposomal formulation development at the 100 mL scale. The goal is not to build highly predictive models, but to rapidly identify robust, workable conditions that enable progression to later development stages. This pragmatic approach reflects the interdependence of manufacturing steps, where downstream processes, such as tangential flow filtration and remote drug loading, may influence or negate prior optimizations.</div><div>By evaluating key parameters like ethanol content, stirring speed, and extrusion conditions, the study offers a practical roadmap for resource-conscious process development, supporting informed decision-making in real-world industrial settings.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"112 ","pages":"Article 107236"},"PeriodicalIF":4.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144534340","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hydrogel microneedles loaded with bFGF and PVP-modified iridium nanoparticles improve follicular microenvironment for androgenetic alopecia treatment","authors":"Shunfu Wang ,&nbsp;Wa Zhang ,&nbsp;Xueting Xie ,&nbsp;Jialu Weng ,&nbsp;Xuchen Deng ,&nbsp;Yizhang Chen ,&nbsp;Xiaoying Niu ,&nbsp;Meilin Yi ,&nbsp;Haobing Li ,&nbsp;Wenzhang Jin","doi":"10.1016/j.jddst.2025.107235","DOIUrl":"10.1016/j.jddst.2025.107235","url":null,"abstract":"<div><div>Androgenetic alopecia (AGA), driven by excessive free radical generation within the hair follicle microenvironment and insufficient perifollicular microvascularization, remains a challenging condition due to the paucity of safe and effective treatment options. In this study, we presented the development of a gelatin methacrylate (GelMA)-based hydrogel-forming microneedles that encapsulated both basic fibroblast growth factor (bFGF) and polyvinylpyrrolidone (PVP)-modified iridium nanoparticles (IrNPs) (Ir/bFGF-MNs). Ir/bFGF-MNs possessed dual functions: alleviating oxidative stress and promoting angiogenesis. These combined effects contributed to the improvement of the perifollicular microenvironment, offering a promising approach for the treatment of AGA. Drawing upon the robust mechanical strength of Ir/bFGF-MNs, these devices penetrated the stratum corneum of the skin, facilitating the efficient delivery of bFGF and IrNPs to both the epidermis and dermis. This delivery system not only eliminated excessive reactive oxygen species (ROS) surrounding the hair follicle but also fostered angiogenesis. Simultaneously, it mechanically stimulated microvessel remodeling within the alopecic region, enhancing the periapical microenvironment. In comparison to clinical treatment with minoxidil for AGA, Ir/bFGF-MNs showed superior efficacy in promoting hair regeneration in AGA model mice. This approach not only enhanced hair quality to a greater extent but also required less frequent dosing and exhibited good biocompatibility. Therefore, Ir/bFGF-MNs is a more effective and convenient therapeutic strategy for AGA, which is informative and potentially applicable in the treatment of alopecia areata-related diseases.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"112 ","pages":"Article 107235"},"PeriodicalIF":4.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144571017","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unveiling the therapeutic potential of Fisetin: Bridging traditional knowledge with modern medicine","authors":"Umesh B. Telrandhe ,&nbsp;Darshan R. Telange ,&nbsp;Vijay Mishra ,&nbsp;Alaa A.A. Aljabali ,&nbsp;Yachana Mishra","doi":"10.1016/j.jddst.2025.107232","DOIUrl":"10.1016/j.jddst.2025.107232","url":null,"abstract":"<div><div>Fisetin (FIS), a pharmacologically active flavonoid present in various fruits and vegetables including strawberries, apples, and persimmons, has attracted considerable attention owing to its broad-spectrum pharmacological activities. Having been traditionally utilized as an antioxidant and anti-inflammatory agent in herbal medicine, FIS is now being developed as a novel therapeutic agent in modern pharmacology. Its wide biological activities involve neuroprotection, antidiabetic, antiobesity, antiatherosclerotic, and significant anticancer activity against lung cancer, colon cancer, prostate cancer, pancreatic cancer, and skin cancer. These activities are mediated through various pathways involving mTOR, Wnt/β-catenin, NF-κB, and TRAIL-induced apoptosis, making FIS a multitargeted pharmacological agent. However, poor solubility and poor bioavailability remain major hurdles in its clinical application. Several novel delivery vehicles including self-nano emulsifying drug delivery systems (SNEDDS), liposomes, ethanol-based delivery vesicles (ethosomes), glycerosomal delivery systems (glycerosomes), and polymeric nanocarriers have been evaluated as vehicles to overcome these limitations. These vehicles significantly increase the solubilizing capacity, stability, and pharmacological efficacy of FIS. Clinical trials have now started evaluating its safety and efficacy in treating osteoarthritis, COVID-19, and chronic kidney disease. This review discusses comprehensively the traditional origin, pharmacodynamic activity, therapeutic applications of FIS, and recent advances in technology involving its formulation vehicles as strong evidence enough to warrant further research as a multipurpose pharmaceutical agent.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"112 ","pages":"Article 107232"},"PeriodicalIF":4.5,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144519147","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intradermal delivery of nanohybrid thermosensitive hydrogels loaded with chondroitin sulphate coated pomegranate lipid carriers via hollow microneedles for effective rheumatoid arthritis management","authors":"Mariam Zewail ,&nbsp;Haidy Abbas ,&nbsp;Nesrine El Sayed ,&nbsp;Nihal M. El Newehy ,&nbsp;Heba Abd-El-Azim","doi":"10.1016/j.jddst.2025.107234","DOIUrl":"10.1016/j.jddst.2025.107234","url":null,"abstract":"<div><div>Rheumatoid Arthritis (RA) is a common inflammatory arthritis type that significantly affects physical functions, leading to restrictions in daily activities. The current study aims to develop an effective nano-based drug delivery system for RA management using pomegranate peel extract (POM). POM was encapsulated in nanostructured lipid carriers (NLCs), coated with chondroitin sulphate (CHS) to actively target CD44 receptors that are over expressed in rheumatic joints. The optimized NLCs were loaded into Pluronic F127 hydrogels to prepare thermosensitive nanohybrid hydrogels for intradermal administration via AdminPen™ MNs hollow microneedles (Ho-MNs). The UPLC-ESI-MS/MS analysis of POM identified 76 compounds, predominantly polyphenols, known for anti-inflammatory and antioxidant properties. NLCs were prepared using the melt emulsification method, showing particle sizes ranging from 64.7 ± 0.34 to 341 ± 2.5 nm, zeta potentials between −17 ± 1.34 mV and −30 ± 0.98 mV, and high entrapment efficiencies (96.34 ± 0.34–98.89 ± 0.12 %). Nanohybrid hydrogels extended the release period of POM from 6 days to 13 days and reduced burst effects. <em>Ex vivo</em> studies confirmed effective skin penetration by AdminPen™ MNs. <em>In vivo</em> studies in rats with AIA demonstrated that POM nanohybrid hydrogels significantly relieved joint swelling and reduced TNF-α, IL-1β, MDA, and MMP-3 levels, while increasing NRF2 level. Histopathological examination revealed that the nanohybrid hydrogel-treated group had normal joint and cartilage structure. This novel system offers a minimally invasive, sustained-release approach for RA treatment, enhancing bioavailability and the therapeutic efficacy of POM, thus providing a promising alternative to conventional therapies.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"112 ","pages":"Article 107234"},"PeriodicalIF":4.5,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144548339","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An in-silico, in-vitro, and in-vivo analysis of hyaluronic acid embedded fucoidan capped silver nanoparticles against periodontal pathogen","authors":"Ritu Mahanty ,&nbsp;Debasmita Dubey ,&nbsp;Ivy Saha ,&nbsp;Rakesh Kumar Sahoo ,&nbsp;Guru Prasanna Sahoo ,&nbsp;Tushar Kanti Rajwar ,&nbsp;Bibhanwita Satpathy ,&nbsp;Jitu Halder ,&nbsp;Ajit Mishra ,&nbsp;Deepak Pradhan ,&nbsp;Priyanka Dash ,&nbsp;Chandan Das ,&nbsp;Salim Manoharadas ,&nbsp;Muralidhar Tata ,&nbsp;Biswakanth Kar ,&nbsp;Goutam Ghosh ,&nbsp;Goutam Rath","doi":"10.1016/j.jddst.2025.107228","DOIUrl":"10.1016/j.jddst.2025.107228","url":null,"abstract":"<div><div>Increasing prevalence of antibiotic resistance among Periodontitis (PDs)-associated microbes poses a significant concern to treatment. Resistance mechanisms, including biofilm and β-lactamase production, hinder disease management. Silver nanoparticles (AgNPs) have been widely explored due to their broad-spectrum antimicrobial properties against resistant microbes. Microbial colonization and the complexity of biofilm in dentin canals limit the permeability of AgNPs and their efficacy. Biosurfactant-mediated AgNPs hold great potential for treating PD-associated infections. In this study, <em>Staphylococcus aureus</em> (<em>S. aureus</em>) was isolated from PDs patients, identified, and characterized by molecular sequencing. AgNPs were prepared using Fucoidan (FN), as it displayed higher binding affinity towards biofilm protein-bap (−3.965) and β- β-lactamase protein-AmpC (−4.331) of <em>S. aureus</em>. The AgNPs were further embedded with Hyaluronic acid (HA) to form a hydrogel matrix. The hydrogel was characterized using various analytical techniques such as UV, SEM, EDX, TEM, FTIR, DSC, DLS and XRD. Stabilized cubic-shaped FN-AgNPs (−36 mV) with a small diameter (85 ± 0.8 nm) exhibited good dispersion (FE-SEM) in HA-matrix and enhanced physicochemical properties. <em>In-Vitro</em> assays suggest the significant antimicrobial (MIC-62.5 μg/mL), antibiofilm (&gt;80 %), and β-lactamase inhibition potential of HA-FN-AgNPs over NB-AgNPs (<em>p</em> ≤ 0.001) against <em>S. aureus</em> without marked cytotoxicity in HGF-1 (∼96 %). Further, <em>In-Vivo</em> findings revealed the superior antimicrobial efficacy, greater mucoadhesion (64 ± 0.56 %) and longer retention efficacy (up to 6 h) of the hydrogel with additional anti-inflammatory properties, suppressing the expression of proinflammatory cytokines (IL-6, IL-1β, and TNF-α), and enhanced drug delivery to PDs pocket. From this study, we conclude that FN-coated-AgNPs synthesized from <em>U. pinnatifida</em> have tremendous potential in drug development.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"112 ","pages":"Article 107228"},"PeriodicalIF":4.5,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144548340","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}