Biomineral-binding liposomes with dual antibacterial effects for preventing and treating dental caries

Dental caries is a chronic oral disease that results from the demineralization of dental hard tissues caused by the long-term interaction of various pathogenic factors in the human oral cavity. Although magnolol (Mag) and fluconazole (FLC) have shown promising antibacterial activity against <i>Candida albicans</i> (<i>C. albicans</i>) and <i>Streptococcus mutans</i> (<i>S. mutans</i>), their clinical application is limited due to hydrophobicity. In this study, we constructed biomineral-binding liposomes co-loaded with Mag and FLC (PPi-Mag/FLC-LPs) to overcome the hydrophobicity and achieve a dual antibacterial activity in the acidic microenvironment of caries. PPi-Mag/FLC-LPs were characterized by laser particle size analysis, transmission electron microscopy, and high-performance liquid chromatography (HPLC). The ability of PPi-Mag/FLC-LPs to bind hydroxyapatite was assessed <i>in vitro</i> using fluorescence microscopy and HPLC, while the antibacterial activity was examined by measuring drug effects on the acidogenicity, acid resistance, biofilm formation and survival of <i>C. albicans</i> and <i>S. mutans</i>. The pharmacodynamics of PPi-Mag/FLC-LPs was also evaluated <i>in vivo</i> in a rat model of dental caries. Mag and FLC were released rapidly from PPi-Mag/FLC-LPs in a pH-sensitive manner, and they bound effectively to hydroxyapatite, leading to a better antibacterial effect on <i>C. albicans</i> and <i>S. mutans</i> compared to free drugs or liposomes loaded with a single drug. PPi-Mag/FLC-LPs improved the medicinal properties of Mag and FLC and provided a rapid, pH-sensitive release of both drugs <i>in vitro</i>. PPi-Mag/FLC-LPs displayed good antibacterial activity <i>in vivo</i>, showing promise as a dual-drug delivery system for the prevention and treatment of caries.