Redox/pH dual-controlled release of chlorhexidine and silver ions from biodegradable mesoporous silica nanoparticles against oral biofilms

Abstract

BackgroundOral 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.PurposeTo 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 methodsCHX-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.ResultsThe 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.ConclusionOur findings constitute a highly effective and safe strategy against biofilms that has a good potential as an oral biofilm therapy.

Lipid-Based Antimicrobial Delivery-Systems for the Treatment of Bacterial Infections

“…Zwitterionic lipids have both acidic and alkaline functional groups (Figure 5; Hu et al, 2019;Makhathini et al, 2019) that allow full charge reversal below and above their iso-electric point (Figure 8A; Vila-Caballer et al, 2016;Liu et al, 2018). This feature allows the fabrication of liposomes that are negatively-charged under physiological pH conditions and become positivelycharged under more acidic conditions, such as poly(methacryloyl sulfadimethoxine) (PSD) liposomes (Figure 8B; Couffin-Hoarau and Leroux, 2004;Ghattas and Leroux, 2009;Lu et al, 2018). Negative charge at physiological pH values aids transport of liposomes through the blood circulation without major interaction with other negatively-charged blood components (Hamal et al, 2019), while adaptation of a positive charge inside the acidic environment of a biofilm facilitates better interaction with negatively-charged bacteria (Robinson et al, 2001;Nederberg et al, 2011;Ng et al, 2013) in the biofilm.…”

Bacteria responsive polyoxometalates nanocluster strategy to regulate biofilm microenvironments for enhanced synergetic antibiofilm activity and wound healing

“…This is attributed to lowered biofilm penetration, which consequently induces bacterial resistance to antibacterial agents and causes antibiotic treatments to fail 9 - 13 . Additionally, because the encapsulation of EPS generates highly acidic niches (pH values close to 4.5), a biofilm microenvironment (BME) that is infected with bacteria is characterized as hypoxic and more acidic than the microenvironment of healthy tissues, and this leads to failure to eradicate infectious disease and to the recurrence of infection 7 , 14 , 15 . Thus, novel anti-biofilm strategies that target bacterial-infected microenvironments are important and have attracted significant interest.…”

Silica Nanoparticles—A Versatile Tool for the Treatment of Bacterial Infections

“…This nanocarrier loaded with ampicillin displayed potent antimicrobial activity against E. coli and S. aureus . In another study, Lu and team fabricated a biodegradable, silver-decorated, chlorhexidine (CHX)-loaded MSN (Ag-MSN@CHX) for oral biofilms with the acidic-redox environment (Lu et al, 2018 ). While the redox microenvironment of the biofilm dismembers the disulfide-bridged framework of MSN, consequently releasing the silver ions, the acidic pH helps in the dissociation of CHX from the carboxyl functional groups of MSN.…”