Objective

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.

Methods

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.

Results

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.

Significance

Our findings indicated that PAMH had great potential to combat early caries lesions in enamel for future clinical application.

中文翻译：

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一种新型抗龋剂，负载和厚朴酚的聚（酰胺胺）树枝状聚合物，用于同时长期抗菌治疗和脱矿牙釉质再矿化

客观的

现有的诱导牙釉质自我修复和早期抑制龋齿进展的药物已被证明是不够的，远不能令人满意。在这项研究中，构建了负载和厚朴酚的聚（酰胺胺）（PAMAM）树枝状聚合物（PAMH）以对抗牙釉质中的早期龋损。

方法

PAMH 是通过共溶法制备的。通过计算模拟分析探索和厚朴酚的释放机制。测试了PAMH的细胞毒性。PAMH 的抗菌作用通过浮游生长试验和生物膜形成抑制试验进行了测试。在 pH 循环模型后，通过横向显微放射照相术和扫描电子显微镜检查 PAMH 的再矿化作用。的体内pamh表示的抗龋齿效果在大鼠模型中进行。

结果

PAMH释放的和厚朴酚在致龋pH环境中比在中性pH环境中更慢但更持久，这可以通过计算模拟分析结果来解释。在静电作用下，带相同电荷的P3珠相互排斥并向外延伸，导致PAMAM树枝状大分子迅速膨胀，加速药物释放。在 5.5 的低 pH 值下，质子化 P3 珠不带电，质子化 P1 珠带正电。然而，质子化的P1珠粒之间的静电排斥相互作用受到PAMAM树枝状大分子最外层的P3珠粒的限制，因此溶胀速度相对较慢，导致药物分子在酸性环境中缓慢释放。动物研究中的细胞毒性证明和生物相容性实验表明，PAMH 是生物安全的。PAMH在pH循环后表现出优异的牙釉质再矿化能力，并显示出长期的抗菌作用体外。同时，PAMH在体内显示出长期的抗龋作用。

意义

我们的研究结果表明，PAMH 在对抗牙釉质早期龋损方面具有巨大潜力，可用于未来的临床应用。