Controlled drug delivery from metronidazole-containing bioactive endodontic cements.

Abstract

This study aims to formulate metronidazole liquid nanocapsules (MTZLNC) and evaluate their effect on the physicochemical and biological properties of calcium silicate-based bioactive endodontic cements, in vitro. A MTZLNC suspension was formulated by deposition of the preformed polymer and characterized by laser diffraction and high-performance liquid chromatography (HPLC). Calcium silicate (CS) was mixed with a radiopaque agent (calcium tungstate - CaWO4), at 10wt%, to produce the cement powder. Cements liquids were used with two concentrations of MTZLNC suspension: 0.3mg/ml and 0.15mg/ml. Cements prepared with distilled water were used as the control. The radiopacity, setting time, and flow were evaluated following ISO 6876:2012. The compressive strength analysis was conducted according to ISO 9917:2007. pH and mineral deposition were evaluated after immersion in simulated body fluid (SBF). Cell behavior was evaluated by the viability of pre-osteoblastic cells and pulp fibroblasts by SRB and MTT and the antibacterial activity against Enterococcus faecalis was analyzed immediately and after nine months of water storage. MTZLNCs were formulated with a median diameter of 148nm and 83.44 % load efficiency. Increased flow and reduced strength were observed for both MTZLNCs concentrations. The incorporation of MTZLNCs maintained the ability of cements to increase pH media and promote mineral deposition over the samples, without promoting cytotoxicity. A 2log10 reduction in E. faecalis CFU was observed immediately and after nine months in water storage. The formulation of MTZLNCs allowed the development of antibacterial calcium silicate-based-cements with suitable physicochemical properties and bioactivity, with a reduction in mechanical strength. The 0.3mg/ml concentration in cements liquid promoted effective and sustainable antibacterial activity.