International Journal of Nanomedicine (Nov 2018)
Redox/pH dual-controlled release of chlorhexidine and silver ions from biodegradable mesoporous silica nanoparticles against oral biofilms
Abstract
Meng-meng Lu,1,2 Yuran Ge,1,2 Jing Qiu,1,2 Dan Shao,3 Yue Zhang,4 Jing Bai,4 Xiao Zheng,5 Zhi-min Chang,3 Zheng Wang,3 Wen-fei Dong,3 Chun-bo Tang1,2 1Department of Oral Implantology, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, 210029, China; 2Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, 210029, China; 3CAS Key Laboratory of Bio-Medical Diagnostics, Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou, 215163, China; 4School of Materials Science and Engineering, Southeast University, Nanjing, 211189, China; 5Department of Pharmacology, Nanomedicine Engineering Laboratory of Jilin Province, College of Basic Medical Sciences, Jilin University, Changchun, 130021, China Background: Oral plaque biofilms pose a threat to periodontal health and are challenging to eradicate. There is a growing belief that a combination of silver nanoparticles and chlorhexidine (CHX) is a promising strategy against oral biofilms.Purpose: To overcome the side effects of this strategy and to exert maximum efficiency, we fabricated biodegradable disulfide-bridged mesoporous silica nanoparticles (MSNs) to co-deliver silver nanoparticles and CHX for biofilm inhibition.Materials and methods: CHX-loaded, silver-decorated mesoporous silica nanoparticles (Ag-MSNs@CHX) were fabricated after CHX loading, and the pH- and glutathione-responsive release profiles of CHX and silver ions along with their mechanism of degradation were systematically investigated. Then, the efficacy of Ag-MSNs@CHX against Streptococcus mutans and its biofilm was comprehensively assessed by determining the minimum inhibitory concentration, minimum bactericidal concentration, minimal biofilm inhibitory concentration, and the inhibitory effect on S. mutans biofilm formation. In addition, the biosafety of nanocarriers was evaluated by oral epithelial cells and a mouse model.Results: The obtained Ag-MSNs@CHX possessed redox/pH-responsive release properties of CHX and silver ions, which may be attributed to the redox-triggered matrix degradation mechanism of exposure to biofilm-mimetic microenvironments. Ag-MSNs@CHX displayed dose-dependent antibacterial activity against planktonic and clone formation of S. mutans. Importantly, Ag-MSNs@CHX had an increased and long-term ability to restrict the growth of S. mutans biofilms compared to free CHX. Moreover, Ag-MSNs@CHX showed less cytotoxicity to oral epithelial cells, whereas orally administered Ag-MSNs exhibited no obvious toxic effects in mice.Conclusion: Our findings constitute a highly effective and safe strategy against biofilms that has a good potential as an oral biofilm therapy. Keywords: biodegradable mesoporous silica nanoparticles, silver nanoparticles, chlorhexidine, GSH, pH-responsive release, biofilm, biocompatibility
