Szymańska Emilia, Potaś Joanna, Baranowski Marcin, Czarnomysy Robert, Sulewska Magdalena Ewa, Basa Anna, Pietruska Małgorzata, Bielawski Krzysztof, Winnicka Katarzyna
Department of Pharmaceutical Technology, Medical University of Białystok, Mickiewicza 2c, 15-222 Białystok, Poland.
Department of Physiology, Medical University of Bialystok, Mickiewicza 2c, 15-222 Białystok, Poland.
Pharmaceutics. 2023 Oct 23;15(10):2512. doi: 10.3390/pharmaceutics15102512.
Photodynamic therapy (PDT) recently has been shown as a promising option in the treatment of premalignant lesions of the soft oral tissues. Effective delivery of photosensitizer is challenging due to poor drug adherence to the oromucosal epithelium. In the present work, emulgels composed of natural polysaccharide gums (tragacanth, xanthan and gellan) were evaluated as novel oromucosal platforms of delta-aminolevulinic acid (ALA) for PDT. Apart from mucoadhesive and textural analysis, the specific steps involved studies on drug penetration behavior and safety profile using a three-dimensional human oral epithelium model (HOE). All designed emulgels presented greater mucoadhesiveness when compared to commercial oromucosal gel. Incorporation of ALA affected textural properties of emulgels, and tragacanth/xanthan formulation with greater hardness and cohesiveness exhibited a protective function against the mechanical tongue stress. Permeability studies revealed that ALA is capable of penetrating across oromucosal epithelium by passive transport and all formulations promoted its absorption rate when compared to a commercial topical product with ALA. Importantly, the combination of tragacanth and xanthan profoundly enhanced photosensitizer retention in the buccal epithelium. Tested samples performed negligible reduction in cell viability and moderately low IL-1β release, confirming their non-irritancy and compatibility with HOE. Overall, the presented findings indicate that tragacanth/xanthan emulgel holds promise as an oromucosal ALA-carrier for PDT strategy.
光动力疗法(PDT)最近已被证明是治疗口腔软组织癌前病变的一种有前景的选择。由于药物对口腔黏膜上皮的粘附性差,光敏剂的有效递送具有挑战性。在本研究中,评估了由天然多糖胶(黄芪胶、黄原胶和结冷胶)组成的乳化凝胶作为δ-氨基乙酰丙酸(ALA)用于PDT的新型口腔黏膜平台。除了粘膜粘附性和质地分析外,具体步骤还包括使用三维人类口腔上皮模型(HOE)研究药物渗透行为和安全性。与市售口腔黏膜凝胶相比,所有设计的乳化凝胶都表现出更大的粘膜粘附性。ALA的加入影响了乳化凝胶的质地特性,具有更高硬度和内聚性的黄芪胶/黄原胶配方对机械性舌压力具有保护作用。渗透性研究表明,ALA能够通过被动转运穿透口腔黏膜上皮,与含ALA的市售局部产品相比,所有配方都提高了其吸收率。重要的是,黄芪胶和黄原胶的组合显著提高了颊上皮中光敏剂的保留率。测试样品对细胞活力的降低可忽略不计,IL-1β释放适度较低,证实了它们的无刺激性以及与HOE的相容性。总体而言,研究结果表明,黄芪胶/黄原胶乳化凝胶有望作为PDT策略的口腔黏膜ALA载体。