Ultrasound activated silica particles for efficient eradication of dental biofilms

Dental infections and diseases are a global health problem, affecting more than 3.5 billion people worldwide. Bacterial biofilms are dominant contributors to oral disease and their treatment is challenging due to increased antimicrobial resistance and reduced efficiency of drug penetration. Low frequency ultrasound is an attractive stimulus for drug delivery systems with controlled, low power that does not interfere with chemical reactivity but may only influence intermolecular chemical interactions in localised applications. We present an ultrasound triggered nanodelivery system for localised treatment of biofilms. Our nanodelivery system is based on an antibacterial agent, cetylpyridinium chloride (CPC), incorporated as micelles within the silica particle framework (m-CPC⊂SiO2) which is only released by application of low frequency ultrasound, circumventing uncontrolled, "burst", drug leakage. Ultrasonic exposure of m-CPC⊂SiO2 from a clinical dental ultrasonic scaler device leads to release of CPC, not observed in the absence of ultrasound. High resolution electron microscopy of m-CPC⊂SiO2 on exposure to ultrasound reveals changes in the structural framework of the particles and reveals voids confirming release of CPC. The antimicrobial efficacy of the m-CPC⊂SiO2 nanosystem is investigated against 72 h single species Streptococcus sanguinis biofilms, a common dental bacterium. The ultrasound-activated m-CPC⊂SiO2 nanosystem shows improved antimicrobial activity leading to a 10 000-fold reduction in colony forming units of bacteria compared to treatment with only CPC. This approach is a transformative strategy for controlled and localised delivery of antibiotics for dental and medical applicatons in different clinical settings.