{"title":"An in-silico, in-vitro, and in-vivo analysis of hyaluronic acid embedded fucoidan capped silver nanoparticles against periodontal pathogen","authors":"Ritu Mahanty , Debasmita Dubey , Ivy Saha , Rakesh Kumar Sahoo , Guru Prasanna Sahoo , Tushar Kanti Rajwar , Bibhanwita Satpathy , Jitu Halder , Ajit Mishra , Deepak Pradhan , Priyanka Dash , Chandan Das , Salim Manoharadas , Muralidhar Tata , Biswakanth Kar , Goutam Ghosh , Goutam Rath","doi":"10.1016/j.jddst.2025.107228","DOIUrl":null,"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 (>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":4.5000,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Drug Delivery Science and Technology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1773224725006318","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
引用次数: 0
Abstract
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, Staphylococcus aureus (S. aureus) 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 S. aureus. 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. In-Vitro assays suggest the significant antimicrobial (MIC-62.5 μg/mL), antibiofilm (>80 %), and β-lactamase inhibition potential of HA-FN-AgNPs over NB-AgNPs (p ≤ 0.001) against S. aureus without marked cytotoxicity in HGF-1 (∼96 %). Further, In-Vivo 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 U. pinnatifida have tremendous potential in drug development.
期刊介绍:
The Journal of Drug Delivery Science and Technology is an international journal devoted to drug delivery and pharmaceutical technology. The journal covers all innovative aspects of all pharmaceutical dosage forms and the most advanced research on controlled release, bioavailability and drug absorption, nanomedicines, gene delivery, tissue engineering, etc. Hot topics, related to manufacturing processes and quality control, are also welcomed.