Coopersmith Sarah, Rahamim Valeria, Drori Eliyahu, Miloslavsky Rachel, Kozlov Rima, Gorelick Jonathan, Azagury Aharon
The Department of Chemical Engineering and Biotechnology, Ariel University, Ariel 4070000, Israel.
Eastern Research & Development Center, Kiryat Arba, Ariel 40700, Israel.
Gels. 2024 Dec 19;10(12):836. doi: 10.3390/gels10120836.
Buccal drug delivery offers a promising alternative for avoiding gastrointestinal degradation and first-pass metabolism. However, enhancing the buccal epithelial barrier's permeability remains challenging. This study explores the effects of ethanolic extracts from (CM), (CMC), and (ORD) on buccal epithelium permeability in vitro using a TR146 cell-based model. The cell viability assay revealed that the extracts were non-toxic at the concentration range tested (<0.5% /). Surprisingly, none of the tested extracts significantly enhanced the buccal permeability of 40 kDa Fluorescein Isothiocyanate Dextran (FD40). However, the CMC and ORD extracts significantly reduced the epithelial permeability of FD40, mirroring the effects of hyaluronic acid (HA), a known barrier integrity enhancer. The total phenolic content (TPC) analysis suggested a potential link between the phenolic concentration and epithelial barrier reinforcement. The rapid colorimetric response method was applied to assess the interaction of these extracts with biological membranes. The results indicated that HA interacts with cellular membranes via lipid bilayer penetration, whereas the extracts likely influence the barrier integrity through alternative mechanisms, such as ligand-receptor interactions or extracellular matrix modulation. These findings highlight the potential of CMC and ORD extracts as natural agents to enhance buccal epithelial integrity. In conclusion, incorporating these extracts into formulations, such as hydrogels, could offer a cost-effective and biocompatible alternative to HA for improving buccal cavity health.
口腔给药为避免胃肠道降解和首过代谢提供了一种有前景的替代方法。然而，提高口腔上皮屏障的通透性仍然具有挑战性。本研究使用基于TR146细胞的模型，探讨了毛喉鞘蕊花（CM）、光果甘草（CMC）和药用牛舌草（ORD）的乙醇提取物对口腔上皮通透性的体外影响。细胞活力测定表明，在所测试的浓度范围内（<0.5% /），提取物无毒。令人惊讶的是，所测试的提取物均未显著提高40 kDa异硫氰酸荧光素葡聚糖（FD40）的口腔通透性。然而，CMC和ORD提取物显著降低了FD40的上皮通透性，这与透明质酸（HA）（一种已知的屏障完整性增强剂）的作用相似。总酚含量（TPC）分析表明酚类浓度与上皮屏障增强之间可能存在联系。采用快速比色反应法评估这些提取物与生物膜的相互作用。结果表明，HA通过脂质双层渗透与细胞膜相互作用，而提取物可能通过其他机制影响屏障完整性，如配体-受体相互作用或细胞外基质调节。这些发现突出了CMC和ORD提取物作为增强口腔上皮完整性的天然剂的潜力。总之，将这些提取物纳入水凝胶等制剂中，可为改善口腔健康提供一种经济高效且生物相容的替代HA的方法。
