Oral mucosal disease is a general term for a type of disease that mainly affects the oral mucosa and surrounding soft tissues. In the treatment of oral mucosal diseases, due to the particularity of the anatomical location, the use of topical administration is relatively simple and convenient; drugs can easily accumulate in the lesions, and at the same time, they can also avoid adverse reactions caused by systemic drug delivery. Topical administration has become an important and even preferred option for the treatment of oral mucosal diseases. There are various types of topically used drugs for oral mucosal diseases, such as glucocorticoids (triamcinolone acetonide), immunomodulatory drugs (tacrolimus), antiseptic drugs (chlorhexidine), pain relievers (lidocaine) and proprietary Chinese medicines (aloe vera gel). Among these drugs, although the most widely used liquid formulations such as gargles and sprays are easy to use, they are not conducive to local retention of drugs due to the particularity of the oral environment and function. Based on this, researchers have continuously improved the dosage form of the drug, and developed a series of semi-solid pharmaceutical preparations such as gels and ointments, some of which have exerted good curative effects in clinical work. In addition, although films, patches and other solid oral mucosal topical pharmaceutical preparations have few clinical applications, they have also been widely researched and described and are expected to become the mainstream dosage form in the future. In general, with the improvement of dosage forms, topical administration is playing an increasingly important role in the treatment of oral mucosal diseases. Therefore, combined with basic research and clinical reports, this article reviews the application of topical drug delivery in the treatment of oral mucosal diseases.

Three-dimensional (3D) epithelial models are widely used to investigate epithelial biology, host-pathogen interactions, and topical therapeutics. However, many existing models rely on primary keratinocytes or specific cell lines, limiting accessibility, reproducibility, and scalability. Besides, reliable oral epithelial models based on stable keratinocyte cell lines remain limited, as most current systems depend on primary cells or organotypic cultures. In this study, we established simplified and reproducible 3D epithelial models using an optimized air-liquid interface (ALI) culture system with two human keratinocyte cell lines, HaCaT (epidermal) and HOK (oral). After culture condition optimization, both cell types maintained stable stratification and differentiation across multiple passages. Histological analysis showed well-organized epithelial architectures with distinct basal and suprabasal layers. Immunofluorescence staining confirmed spatially distinct expression of epithelial differentiation markers closely resembling native epithelia. Functionally, the reconstructed epithelia robust barrier integrity and responded to Candida albicans infection. Moreover, the models allowed evaluation of drug permeability across epithelial layers. Collectively, this simplified 3D culture platform provides a reproducible, accessible strategy for constructing epithelial models using standardized keratinocyte cell lines without primary cells. The system offers a practical tool for oral and cutaneous epithelial research, with potential in infection studies, disease modeling, and preclinical drug screening.