Controlled drug delivery from metronidazole-containing bioactive endodontic cements

Gabriela Souza Balbinot; Vicente Castelo Branco Leitune; Kelly Cristina Zatta; Tainara Benin; Silvia Stanisçauski Guterres; Fabricio Mezzomo Collares

doi:10.1016/j.dental.2023.07.006

Controlled drug delivery from metronidazole-containing bioactive endodontic cements

Dent Mater. 2023 Sep;39(9):839-845. doi: 10.1016/j.dental.2023.07.006. Epub 2023 Jul 26.

Authors

Gabriela Souza Balbinot¹, Vicente Castelo Branco Leitune¹, Kelly Cristina Zatta², Tainara Benin³, Silvia Stanisçauski Guterres⁴, Fabricio Mezzomo Collares⁵

Affiliations

¹ Department of Dental Materials, School of Dentistry, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
² Cosmetology and Pharmaceutical Nanotechnology Laboratory, School of Pharmaceutical Sciences, Universidade Federal do Rio Grande do Sul, Av. Ipiranga 2752, 90610-000 Porto Alegre, RS, Brazil.
³ Pharmaceutical Nanotechnology Laboratory, School of Pharmaceutical Sciences, Universidade Federal do Rio Grande do Sul, Av. Ipiranga 2752, 90610-000 Porto Alegre, RS, Brazil.
⁴ Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil; Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil.
⁵ Department of Dental Materials, School of Dentistry, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil. Electronic address: fabricio.collares@ufrgs.br.

PMID: 37500315
DOI: 10.1016/j.dental.2023.07.006

Abstract

Objectives: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords: Calcium silicate; Dental pulp capping; Drug delivery systems; Metronidazole; Regenerative endodontics.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Anti-Bacterial Agents / chemistry
Anti-Bacterial Agents / pharmacology
Calcium Compounds* / chemistry
Calcium Compounds* / pharmacology
Dental Cements / chemistry
Materials Testing
Metronidazole* / pharmacology
Silicates / chemistry
Silicates / pharmacology
Water

Substances

calcium silicate
Metronidazole
Calcium Compounds
Silicates
Dental Cements
Water
Anti-Bacterial Agents