Quaternary ammonium compounds : antibiofilm activity, nanoparticulate drug delivery and perspectives

Abstract

Oral diseases including dental caries and endodontic infections remain prevalent worldwide, leading to a substantial public healthcare burden. The biofilm-mediated nature of these infections makes current treatment strategies less effective and there is a constant search for the design and discovery of novel antimicrobials and their delivery strategies. Quaternary ammonium compounds (QACs) are cationic biocides with an extensive spectrum of antibacterial, antifungal and antiviral activity. The first aim of this thesis was to characterize the antibiofilm activity of QACs. We tested one novel (miramistin) and two conventional QACs (benzalkonium chloride and cetylpyridinium chloride) against microbial biofilms associated with dental infections. The effective antimicrobial concentrations and biocompatibility of each chemical were determined. A key advantage of these QACs is that they act as surfactants possessing amphiphilic properties, which allows them to form micelles in solutions, that can be used as templates for the synthesis of mesoporous silica nanoparticles (MSNs). MSNs have excellent physicochemical properties such as high surface area, mesoporous structure for drug loading and release, and biocompatibility. MSNs synthesized from the target QACs drugs by one step process with high loading of the drug are promising drug delivery vehicles to fight oral biofilms. Therefore, the second aim of this thesis was to load QACs within mesoporous silica nanocarriers and characterize their antimicrobial activity. Based on the results of the first study, we synthesized and characterized the MSN with miramistin and cetylpyridinium chloride. These newly-prepared MSNs with high loading capacity of the QACs showed potent antibacterial and antibiofilm activity. We also further demonstrated the proof-of-concept that these QAC-loaded MSNs can effectively penetrate into dentinal tubules, indicating potential translation into clinical application. In conclusion, for the first time, we report the antibiofilm activity of a new QAC, miramistin, in comparison with commonly clinically used QACs. We further demonstrated that QACs loaded in mesoporous silica nanocarriers have a high percentage loading which suggests their use as drug delivery vehicles to fight biofilms and overcome a number of major challenges such as delivery of chemicals to anatomical complexities within the tooth.