Oral lichen planus (OLP) is an ongoing and chronic inflammatory disease affecting the mucous membrane of the oral cavity. Currently, the treatment of choice consists in the direct application into the buccal cavity of semisolid formulations containing a corticosteroid molecule to decrease inflammatory signs and symptoms. However, this administration route has shown various disadvantages limiting its clinical use and efficacy. Indeed, the frequency of application and the incorrect use of the preparation may lead to a poor efficacy and limit the treatment compliance. Furthermore, the saliva clearance and the mechanical stress present in the buccal cavity also involve a decrease in the mucosal exposure to the drug. In this context, the design of a new pharmaceutical formulation, containing a steroidal anti-inflammatory, mucoadhesive, sprayable and exhibiting a sustained and controlled release seems to be suitable to overcome the main limitations of the existing pharmaceutical dosage forms. The present work reports the formulation, optimization and evaluation of the mucoadhesive and release properties of a poloxamer 407 thermosensitive hydrogel containing a poorly water-soluble corticosteroid, dexamethasone acetate (DMA), threaded into hydroxypropyl-beta-cyclodextrin (HP-β-CD) molecules. Firstly, physicochemical properties were assessed to ensure suitable complexation of DMA into HP-β-CD cavities. Then, rheological properties, in the presence and absence of various mucoadhesive agents, were determined and optimized. The hydration ratio (0.218–0.191), the poloxamer 407 (15–17 wt%) percentage and liquid-cyclodextrin state were optimized as a function of the gelation transition temperature, viscoelastic behavior and dynamic flow viscosity. Deformation and resistance properties were evaluated in the presence of various mucoadhesive compounds, being the sodium alginate and xanthan gum the most suitable to improve adhesion and mucoadhesion properties. Xanthan gum was shown as the best agent prolonging the hydrogel retention time up to 45 min. Furthermore, xanthan gum has been found as a relevant polymer matrix controlling drug release by diffusion and swelling processes in order to achieve therapeutic concentration for prolonged periods of time.

中文翻译：

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基于粘膜黏膜泊洛沙姆的水凝胶可释放HP-β-CD复杂的地塞米松，以治疗口腔疾病。

口腔扁平苔藓（OLP）是一种持续发生的慢性炎症性疾病，会影响口腔粘膜。当前，选择的治疗包括将含有皮质类固醇分子的半固体制剂直接施用到颊腔中，以减少炎症迹象和症状。但是，这种给药途径已显示出各种缺点，限制了其临床用途和功效。实际上，施用频率和制剂的不正确使用可能导致疗效差并限制治疗依从性。此外，存在于口腔中的唾液清除率和机械应力也涉及粘膜暴露于药物的减少。在此背景下，设计了一种新的药物制剂，其中包含甾体类抗炎药，粘膜粘附剂，喷雾剂并表现出持续和控制释放似乎适合克服现有药物剂型的主要限制。本工作报告了泊洛沙姆407热敏水凝胶的粘膜粘附和释放特性的配制，优化和评估，该凝胶包含水溶性差的皮质类固醇醋酸地塞米松（DMA），并插入羟丙基-β-环糊精（HP-β-CD）中分子。首先，评估其理化性质以确保DMA适当地复合到HP-β-CD腔中。然后，确定和优化在存在和不存在各种粘膜粘附剂的情况下的流变性质。水合比（0.218–0.191），泊洛沙姆407（15-17 wt％）的百分比和液体环糊精状态根据凝胶转变温度，粘弹性和动态流动粘度进行了优化。在各种粘膜粘附性化合物的存在下评估了变形和抵抗特性，其中藻酸钠和黄原胶最适合于改善粘着性和粘膜粘附性。黄原胶被证明是将水凝胶保留时间延长至45分钟的最佳药物。此外，已经发现黄原胶是相关的聚合物基质，其通过扩散和溶胀过程来控制药物的释放，以便在较长时间内达到治疗浓度。在各种粘膜粘附性化合物的存在下评估了变形和抵抗性能，其中藻酸钠和黄原胶最适合于改善粘附性和粘膜粘附性。黄原胶被证明是将水凝胶保留时间延长至45分钟的最佳药物。此外，已经发现黄原胶是相关的聚合物基质，其通过扩散和溶胀过程来控制药物的释放，以便在较长时间内达到治疗浓度。在各种粘膜粘附性化合物的存在下评估了变形和抵抗性能，其中藻酸钠和黄原胶最适合于改善粘附性和粘膜粘附性。黄原胶被证明是将水凝胶保留时间延长至45分钟的最佳药物。此外，已经发现黄原胶是相关的聚合物基质，其通过扩散和溶胀过程来控制药物的释放，以便在较长时间内达到治疗浓度。