A novel anticaries agent, honokiol-loaded poly(amido amine) dendrimer, for simultaneous long-term antibacterial treatment and remineralization of demineralized enamel

Existing agents to induce enamel self-repair and inhibit the progression of dental caries in the early stage have been proven to be inadequate and far from satisfactory. In this study, a honokiol-loaded poly(amido amine) (PAMAM) dendrimer (PAMH) was constructed to combat early caries lesions in enamel. PAMH was prepared via a codissolution method. Computational simulation analysis was used to explore the mechanism of honokiol release. The cytotoxicity of PAMH was tested. The antibacterial effects of PAMH were tested by planktonic growth assays and biofilm formation inhibition assays. The remineralization effect of PAMH was examined via transverse microradiography and scanning electron microscopy after a pH cycling model. The in vivo anti-caries effect of PAMH was carried out in a rat model. Honokiol released from PAMH was slower but more durable in a cariogenic pH environment than in a neutral pH environment, which could be explained through the computational simulation analysis results. Under electrostatic action, P3 beads with the same charge repelled each other and extended outwards, resulting in the rapid expansion of the PAMAM dendrimer and accelerating the release of the drug. At a low pH of 5.5, the protonated P3 beads were not charged and the protonated P1 beads were positively charged. However, the electrostatic repulsive interaction between protonated P1 beads was restricted by the P3 beads in the outermost layer of the PAMAM dendrimer, so the swelling rate was relatively slow, resulting in the slow release of drug molecules in the acidic environment. The cytotoxicity demonstration and the biocompatibility experiment in animal study showed that PAMH is biologically safe. PAMH showed excellent enamel remineralizing ability after pH cycling and showed a long-term antibacterial effect in vitro. Meanwhile, PAMH showed long-term anticaries efficacy in vivo. Our findings indicated that PAMH had great potential to combat early caries lesions in enamel for future clinical application.