Manus Lisa M, Daep Carlo Amorin, Begum-Gafur Rehana, Makwana Ekta, Won Betty, Yang Ying, Huang Xiao Yi, Maloney Venda, Trivedi Harsh M, Wu Donghui, Masters James G
Colgate-Palmolive Technology Center, Piscataway, NJ, USA and Colgate-Palmolive Technology Center, Guangzhou, China.
J Clin Dent. 2018 Sep;29(Spec No A):A10-19.
To investigate bioavailability enhancement of zinc on model oral surfaces and in oral biofilms in vitro through strategic formulation with two sources of zinc and L-arginine.
To modulate the bioavailability of active zinc ions in a zinc citrate dentifrice, an additive research strategy was pursued. A series of zinc citrate dentifrice formulations were prepared with increasing replacement of zinc citrate with zinc oxide (a water insoluble source of zinc ions) to generate a Dual Zinc active system. A screening of isolated zinc and amino acid effects in simple solutions using zeta potential and uptake to model oral surfaces was performed in an effort to determine the effect of particle charge on zinc bioavailability. Zinc delivery and antibacterial efficacy of the Dual Zinc plus Arginine dentifrice formula were tested using in vitro oral epithelial tissue and saliva-derived biofilm models. Furthermore, zinc penetration and retention were determined by subjecting in vitro biofilms to dynamic flow after treatment with the Dual Zinc plus Arginine dentifrice with treated biofilms evaluated for zinc using imaging mass spectrometry (I-MS). Bacterial adhesion to gingival epithelial cells treated with the Dual Zinc plus Arginine dentifrice was imaged upon challenging with Streptococcus gordonii.
Addition of zinc oxide into a zinc citrate dentifrice formula enhanced the efficacy of the system against anaerobic biofilms in a concentration- dependent manner. L-arginine further provided a significant positive charge (+36 mV) to the zinc oxide suspension (+16 mV) as measured by zeta potential. Simple solutions of the Dual Zinc active showed increased zinc uptake on model oral surfaces as a direct function of L-arginine concentration. Antibacterial efficacy of a Dual Zinc plus Arginine dentifrice was evaluated through multiple mechanisms. Enhanced antibacterial performance was observed through significant reductions in metabolic activity as measured through bacterial glycolytic function (p = 0.0001) and total oxygen consumption (p = 0.0001). Greater penetration and retention of zinc was observed in bacterial biofilms treated with the Dual Zinc plus Arginine dentifrice in comparison to treatment with a Dual Zinc dentifrice after twelve hours of dynamic flow (10 mL/hour) in an in vitro drip flow biofilm culture. Confocal microscopy showed adherent bacteria on cheek cells treated with the Dual Zinc plus Arginine dentifrice formula.
The combination of zinc citrate, zinc oxide, and the amino acid L-arginine in a dentifrice formula enhances the bioavailability of zinc to model oral tissue surfaces, resulting in unique physicochemical effects. The significant antimicrobial control associated with the Dual Zinc plus Arginine dentifrice provides a unique vehicle toward achieving whole mouth health.
通过将两种锌源与L-精氨酸进行策略性配方，研究锌在体外模型口腔表面和口腔生物膜中的生物利用度增强情况。
为调节柠檬酸锌牙膏中活性锌离子的生物利用度，采用了添加剂研究策略。制备了一系列柠檬酸锌牙膏配方，用氧化锌（一种水不溶性锌离子源）逐步替代柠檬酸锌，以生成双锌活性体系。在简单溶液中，利用zeta电位和对模型口腔表面的摄取来筛选分离的锌和氨基酸的作用，以确定颗粒电荷对锌生物利用度的影响。使用体外口腔上皮组织和唾液衍生生物膜模型测试双锌加精氨酸牙膏配方的锌递送和抗菌功效。此外，在用双锌加精氨酸牙膏处理后，通过对体外生物膜进行动态流动，然后用成像质谱（I-MS）对处理后的生物膜进行锌评估，来确定锌的渗透和保留情况。在用戈登链球菌攻击后，对用双锌加精氨酸牙膏处理的牙龈上皮细胞上的细菌粘附情况进行成像。
在柠檬酸锌牙膏配方中添加氧化锌以浓度依赖的方式增强了该体系对厌氧生物膜的功效。通过zeta电位测量，L-精氨酸进一步为氧化锌悬浮液（+16 mV）提供了显著的正电荷（+36 mV）。双锌活性体系的简单溶液显示，在模型口腔表面上锌的摄取量随L-精氨酸浓度的增加而增加。通过多种机制评估了双锌加精氨酸牙膏的抗菌功效。通过细菌糖酵解功能（p = 0.0001）和总氧消耗（p = 0.0001）测量的代谢活性显著降低，观察到抗菌性能增强。与双锌牙膏处理相比，在体外滴流生物膜培养中进行12小时动态流动（10毫升/小时）后，用双锌加精氨酸牙膏处理的细菌生物膜中观察到锌的渗透和保留更多。共聚焦显微镜显示，在用双锌加精氨酸牙膏配方处理的脸颊细胞上有粘附的细菌。
牙膏配方中柠檬酸锌、氧化锌和氨基酸L-精氨酸的组合提高了锌对模型口腔组织表面的生物利用度，产生了独特的物理化学效应。与双锌加精氨酸牙膏相关的显著抗菌控制为实现全口健康提供了一种独特的手段。
