Cancer, a major world public health problem, is associated with chemotherapy treatments whose administration leads to secondary concerns, such as oral mucositis (OM). The OM disorder is characterized by the presence of ulcers in the oral mucosa that cause pain, bleeding, and difficulty in ingesting fluids and solids, or speaking. Bioactive compounds from natural sources have arisen as an effective approach for OM. This review aims to summarize the new potential application of different natural products in the prevention and treatment of OM in comparison to conventional ones, also providing a deep insight into the most recent clinical studies. Natural products, such as Aloe vera, Glycyrrhiza glabra, Camellia sinensis, Calendula officinalis, or honeybee crops, constitute examples of sources of bioactive compounds with pharmacological interest due to their well-reported activities (e.g., antimicrobial, antiviral, anti-inflammatory, analgesic, or wound healing). These activities are associated with the bioactive compounds present in their matrix (such as flavonoids), which are associated with in vivo biological activities and minimal or absent toxicity. Finally, encapsulation has arisen as a future opportunity to preserve the chemical stability and the drug bioa vailability of bioactive compounds and, most importantly, to improve the buccal retention period and the therapeutic effects.

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The proposed study aims to develop and optimize a topical formulation with Castanea sativa shells extract considering the concept of Quality by Design, focusing on a planned development that consider the vulnerabilities of the entire process through risk analysis tools and design of experiments (DoE). A Box–Behnken design with three factors and three levels was used as a statistical tool for the execution of the DoE and the analysis of the response surface methodology responses. The independent variables studied were the quantity of sodium lauryl sulfate (%) (X1), beeswax (%) (X2) and macadamia oil (%) (X3); the dependent variables were pH (Y1), viscosity (Y2) and adhesiveness (Y3). According to the mathematical model, the optimal formulation contains 0.93% of sodium lauryl sulfate, 5.00% of beeswax and 10.00% of macadamia oil. The optimal formulation with the extract was prepared and characterized over the time, regarding organoleptic and technological characteristics, allowing conclusions to be reached regarding its stability. The formulation presented a pleasant odor and was light brown in color, it also demonstrated pseudoplastic-thixotropic behavior and a small reduction in the formulation consistency after 30 days of storage. This study demonstrated the efficiency of the Quality by Design methodology to understand the product variability, supporting that this approach favors a better understanding of the whole process and enables to design a robust development stage, reducing costs and generating high-quality products.