pH Dependent Delivery of Chlorhexidine From PLGA Grafted Mesoporous Silica Nanoparticles at Resin-Dentin Interface
Abstract Background: A low pH environment is created due to the production of acids by oral biofilms that further leads to the dissolution of hydroxyapatite crystal in the tooth structure significantly altering the equilibrium. Although the overall bacterial counts may not be eradicated completely from the oral cavity, however, synthesis of engineered anti-bacterial materials are warranted in order to reduce the pathogenic impact of the oral biofilms. The purpose of this study was to synthesize and characterize chlorhexidine-loaded mesoporous silica nanoaprticles (MSN) grafted with poly-L-glycolic acid (PLGA) and to test the in vitro drug release in various pH environments, cytotoxicity, and antimicrobial capacity. In addition, to investigate the delivery of CHX-loaded/MSN-PLGA through dentin tubules of demineralized dentin substrates and the interaction of these nanoparticles with commercial dentin adhesive after applying it on demineralized substrates for potential clinical application.Results: Characterization using SEM/TEM and EDX confirmed the synthesis of CHX-loaded/MSN-PLGA. An increase in the percentage of drug encapsulation efficiency from 81% to 85% in CHX loaded/MSN and 92% to 95% in CHX loaded/MSN-PLGA proportionately increased with increasing the amount of CHX during the fabrication of nanoparticles. For both time-periods (24 h or 30 Days), the relative microbial viability significantly decreased by increasing the CHX content (P<0.001). Generally, the cell viability percentage of DPSCs exposed to MSN-PLGA/Blank, CHX-loaded/MSN, and CHX-loaded/MSN-PLGA, respectively was >80% indicating low cytotoxicity profiles of experimental nanoparticles. After 9 months in artificial saliva (pH 7.4), significantly highest micro-tensile bond strength value was recorded for 25:50 CHX/MSN and 25:50:50 CHX/MSN-PLGA. A homogenous and widely distributed 50:50:50 CHX-loaded/MSN-PLGA nanoparticles exhibited excellent bonding with the application of commercially available dentin adhesive.Conclusions: A pH sensitive CHX release response was noted when loaded in MSN grafted PLGA nanoparticles. The formulated drug loaded nanocarrier demonstrated excellent physicochemical, spectral, and biological characteristics. Showing considerable capacity to penetrate effectively inside dentinal tubules and having high antibacterial efficacy, this system could be potentially used in adhesive and restorative dentistry.