Tetyczka Carolin, Hartl Sonja, Jeitler Ramona, Absenger-Novak Markus, Meindl Claudia, Fröhlich Eleonore, Riedl Sabrina, Zweytick Dagmar, Roblegg Eva
Institute of Pharmaceutical Sciences, Department of Pharmaceutical Technology and Biopharmacy, University of Graz, 8010 Graz, Austria.
Center for Medical Research, Medical University of Graz, 8010 Graz, Austria.
Nanomaterials (Basel). 2021 May 18;11(5):1330. doi: 10.3390/nano11051330.
Topical drug administration to the oral mucosa proves to be a promising treatment alternative for inflammatory diseases. However, disease-related changes in the cell barrier must be considered when developing such delivery systems. This study aimed at investigating the changes in the lining mucosa caused by inflammation and evaluating the consequences on drug delivery systems such as nanostructured lipid carriers (NLC). For this, TR146 cells were treated with inflammatory cytokines and bacterial components. Cell viability and integrity, reactive oxygen species (ROS), and interleukin (IL)-8 release were used as endpoints to assess inflammation. Translocation of phosphatidylserine, cytoskeletal arrangement, opening of desmosomes, and cell proliferation were examined. Transport studies with NLC were performed considering active and passive pathways. The results showed that IL-1ß and tumor necrosis factor α induced inflammation by increasing IL-8 and ROS production (22-fold and 2-fold). Morphologically, loss of cell-cell connections and formation of stress fibers and hyperplasia were observed. The charge of the cell membrane shifted from neutral to negative, which increased the absorption of NLC due to the repulsive interactions between the hydrophobic negative particles and the cell membrane on the one hand, and interactions with lipophilic membrane proteins such as caveolin on the other.
向口腔黏膜局部给药被证明是治疗炎症性疾病的一种有前景的替代方法。然而，在开发此类给药系统时，必须考虑细胞屏障中与疾病相关的变化。本研究旨在调查炎症引起的衬里黏膜变化，并评估其对纳米结构脂质载体（NLC）等药物递送系统的影响。为此，用炎性细胞因子和细菌成分处理TR146细胞。细胞活力和完整性、活性氧（ROS）以及白细胞介素（IL）-8释放被用作评估炎症的终点指标。检测了磷脂酰丝氨酸的易位、细胞骨架排列、桥粒的开放以及细胞增殖情况。考虑主动和被动途径进行了NLC的转运研究。结果表明，IL-1β和肿瘤坏死因子α通过增加IL-8和ROS的产生（分别为22倍和2倍）诱导炎症。在形态学上，观察到细胞间连接丧失、应力纤维形成和增生。细胞膜电荷从中性转变为阴性，一方面由于疏水性负性颗粒与细胞膜之间的排斥相互作用，另一方面与脂膜蛋白如小窝蛋白相互作用，从而增加了NLC的吸收。
