School of Clinical Dentistry, University of Sheffield, Sheffield, UK.
Faculty of Dentistry, Universiti Sains Islam Malaysia, Kuala Lumpur, Malaysia.
Eur J Oral Sci. 2021 Apr;129(2):e12761. doi: 10.1111/eos.12761. Epub 2021 Mar 1.
Oral lichen planus (OLP) is an immune-mediated disease of the oral mucosa with idiopathic aetiology. It is frequently treated with topical corticosteroids (applied as gels, mouthwashes, or sprays); however, the mucosal exposure times of topical corticosteroids are short because of removal by the constant flow of saliva and mechanical forces. In this study we used cell monolayers, as well as oral mucosal equivalents (OMEs) containing activated T-cells, to examine corticosteroid potency and delivery of clobetasol-17-propionate from a novel electrospun mucoadhesive patch. The OMEs displayed tight junctions, desmosomes, hemidesmosomes, and an efficient permeability barrier. Following application of corticosteroids to cells cultured as monolayers, the degree of cytotoxicity measured correlated to the level of potency recognized for each corticosteroid; by contrast, OMEs were largely unaffected by corticosteroid treatment. Permeation of clobetasol-17-propionate into and through the OMEs was time- and dose-dependent, regardless of whether this corticosteroid was delivered in liquid form or from a mucoadhesive patch, and both liquid- and patch-delivered clobetasol-17-propionate significantly reduced the secretion of interleukin-2 by activated T-cells. This study confirms that OMEs are more suitable models than cell monolayers for evaluating toxicity and drug delivery. After topical exposure, clobetasol-17-propionate accumulated in OMEs at a higher level than betamethasone-17-valerate and hydrocortisone-17-valerate, and exerted its immunosuppressive actions following application via the patch delivery system, highlighting the efficacy of this mode of drug delivery to treat OLP.
口腔扁平苔藓（OLP）是一种特发性病因的口腔黏膜免疫介导疾病。它常采用局部皮质类固醇治疗（作为凝胶、漱口液或喷雾剂应用）；然而，由于唾液的持续流动和机械力的作用，局部皮质类固醇的黏膜暴露时间很短。在这项研究中，我们使用细胞单层以及含有活化 T 细胞的口腔黏膜等效物（OME），来研究从新型电纺型黏附性贴剂中释放氯倍他索-17-丙酸酯的皮质类固醇效力和传递。OME 显示出紧密连接、桥粒、半桥粒和有效的渗透性屏障。在将皮质类固醇应用于作为单层培养的细胞后，测量的细胞毒性程度与每个皮质类固醇的效力水平相关；相比之下，OME 受皮质类固醇处理的影响不大。氯倍他索-17-丙酸酯渗透进入和穿过 OMEs 是时间和剂量依赖性的，无论这种皮质类固醇是液体形式还是从黏附性贴剂中递送，液体和贴剂递送的氯倍他索-17-丙酸酯都显著减少了活化 T 细胞的白细胞介素-2 的分泌。这项研究证实，OME 比细胞单层更适合用于评估毒性和药物传递。在局部暴露后，氯倍他索-17-丙酸酯在 OME 中的积累水平高于倍他米松-17-戊酸酯和氢化可的松-17-戊酸酯，并且在通过贴剂递送系统应用后发挥其免疫抑制作用，突出了这种药物递送模式治疗 OLP 的疗效。
