Philip Morris International R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, 2000, Neuchâtel, Switzerland.
Food Chem Toxicol. 2021 Nov;157:112577. doi: 10.1016/j.fct.2021.112577. Epub 2021 Sep 24.
Trehalose is added in drug formulations to act as fillers or improve aerosolization performance. Its characteristics as a carrier molecule have been explored; however, the fate of trehalose in human airway tissues has not been thoroughly investigated. Here, we investigated the fate of nebulized trehalose using in vitro human air-liquid bronchial epithelial cultures. First, a tracing experiment was conducted using C-trehalose; we measured trehalose distribution in different culture compartments (apical surface liquid, epithelial culture, and basal side medium) at various time points following acute exposure to C-labeled trehalose. We found that C-trehalose was metabolized into C-glucose. The data was then used to model the kinetics of trehalose disappearance from the apical surface of bronchial cultures. Secondly, we evaluated the potential adverse effects of nebulized trehalose on the bronchial cultures after they were acutely exposed to nebulized trehalose up to a level just below its solubility limit (50 g/100 g water). We assessed the ciliary beating frequency and histological characteristics. We found that nebulized trehalose did not lead to marked alteration in ciliary beating frequency and morphology of the epithelial cultures. The in vitro testing approach used here may enable the early selection of excipients for future development of inhalation products.
海藻糖被添加到药物制剂中，用作填充剂或改善雾化性能。它作为载体分子的特性已经被探索过；然而，海藻糖在人体气道组织中的命运还没有被彻底研究过。在这里，我们使用体外人液支气管上皮细胞培养物研究了雾化海藻糖的命运。首先，我们进行了一项示踪实验，使用 C-海藻糖；我们在急性暴露于 C 标记的海藻糖后，在不同的时间点测量了不同培养区室（顶端表面液体、上皮培养物和基底侧培养基）中的海藻糖分布。我们发现 C-海藻糖被代谢成 C-葡萄糖。然后，我们使用这些数据来模拟海藻糖从支气管培养物顶端表面消失的动力学。其次，我们评估了急性暴露于低于其溶解度极限（50g/100g 水）的雾化海藻糖后，雾化海藻糖对支气管培养物的潜在不良影响。我们评估了纤毛摆动频率和组织学特征。我们发现，雾化海藻糖不会导致纤毛摆动频率和上皮培养物形态明显改变。这里使用的体外测试方法可能能够早期选择吸入产品开发的赋形剂。
