Controlled drug delivery from metronidazole-containing bioactive endodontic cements

This study aims to formulate metronidazole liquid nanocapsules (MTZ_LNC) and evaluate their effect on the physicochemical and biological properties of calcium silicate-based bioactive endodontic cements, in vitro.

A MTZ_LNC 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 10 wt%, to produce the cement powder. Cements liquids were used with two concentrations of MTZ_LNC suspension: 0.3 mg/ml and 0.15 mg/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.

MTZ_LNCs were formulated with a median diameter of 148 nm and 83.44 % load efficiency. Increased flow and reduced strength were observed for both MTZ_LNCs concentrations. The incorporation of MTZ_LNCs maintained the ability of cements to increase pH media and promote mineral deposition over the samples, without promoting cytotoxicity. A 2 log₁₀ reduction in E. faecalis CFU was observed immediately and after nine months in water storage.

The formulation of MTZ_LNCs allowed the development of antibacterial calcium silicate-based-cements with suitable physicochemical properties and bioactivity, with a reduction in mechanical strength. The 0.3 mg/ml concentration in cements liquid promoted effective and sustainable antibacterial activity.