International Journal of Nanomedicine (Feb 2022)
Silver Nanoparticles as Chlorhexidine and Metronidazole Drug Delivery Platforms: Their Potential Use in Treating Periodontitis
Abstract
Karol P Steckiewicz,1 Piotr Cieciórski,2 Ewelina Barcińska,1 Maciej Jaśkiewicz,3 Magdalena Narajczyk,4 Marta Bauer,3 Wojciech Kamysz,3 Elżbieta Megiel,2 Iwona Inkielewicz-Stepniak1 1Department of Pharmaceutical Pathophysiology, Faculty of Pharmacy, Medical University of Gdansk, Gdansk, Poland; 2Faculty of Chemistry, University of Warsaw, Warsaw, Poland; 3Department of Inorganic Chemistry, Faculty of Pharmacy, Medical University of Gdansk, Gdansk, Poland; 4Laboratory of Electron Microscopy, Faculty of Biology, University of Gdansk, Gdansk, PolandCorrespondence: Iwona Inkielewicz-Stepniak Tel +48 58 349 1516Fax +48 58 349 1517Email [email protected]: Periodontal disease (PD), defined as oral inflammation caused by dental plaque, is an emerging problem. PD may lead to tooth loss, and treatment options are limited. In this study, we designed, synthesized, and characterized silver nanoparticles (AgNPs) conjugated with chlorhexidine (AgNPs-CHL) or metronidazole (AgNPs-PEG-MET) to determine whether they can be used to treat PDs.Materials and Methods: AgNPs were synthesized and characterized by transmission electron microscopy, UV-vis spectrometry, thermogravimetric analyses, and dynamic light scattering. We determined the safety and the antimicrobial and anti-inflammatory properties of synthesized AgNPs in an in vitro model of periodontitis. Antimicrobial properties were determined by measuring the minimum inhibitory concentration (MIC) and minimum biofilm eradication concentration (MBEC) on reference strains of bacteria and fungi. Human gingival fibroblast (HGF-1), murine macrophage (RAW264.7) and human foetal osteoblast (hFOB1.19) cells were used in the study. Lipopolysaccharide (LPS) was used to induce inflammation. Cytokine levels were measured using an enzyme-linked immunosorbent assay; metalloproteinase expression was measured using Western blotting.Results: The synthesized AgNPs were spherical and narrow-dispersed with an average diameter of 13.4 nm ± 3.0 nm in the case of AgNPs-CHL and 3.72 nm ± 0.72 nm in the case of AgNPs-PEG-MET. Both types of AgNPs were active against bacteria and fungi. AgNPs-CHL proved to be a more potent antimicrobial agent, although they were more cytotoxic than AgNPs-PEG-MET; however, both demonstrated beneficial properties in nontoxic concentrations. AgNPs-CHL and AgNPs-PEG-MET decreased the production of proinflammatory cytokines IL-1β, IL-6, IL-8 and TNFα. Both agents also decreased the levels of metalloproteinases MMP3 and MMP8, which may indicate that they will inhibit tissue degradation.Conclusion: AgNPs-CHL and AgNPs-PEG-MET may be possible therapeutic options for PD, as they have antibacterial and anti-inflammatory properties. However, to fully understand the potential of AgNPs, our in vitro findings must be evaluated in an in vivo model.Keywords: drug delivery platforms, gingival fibroblast, macrophages, osteoblasts, periodontal disease, periodontitis
