## 5 Topical Curcumin-Based Formulations in Oral Diseases
### Oral Mucositis and Mouth Ulcers  
The origin of oral inflammations is very complex due to multiple factors which have negative influence on the functioning of oral epithelium, flora condition or the immune system. The most frequently mentioned are inappropriate lifestyle and diet, poor oral hygiene, injuries, dental problems or neoplastic changes (ulcers). In the latter case, the risk of inflammation results not only from the existing disease but mainly from the applied therapy [130; 131]. About 10-40% of patients undergoing chemotherapy, depending on whether it is basic or adjuvant, suffer from oral inflammation. In the case of patients receiving radiotherapy in head and neck cancer, when the radiation covers the oral cavity, the inflammation symptoms can be observed in almost 100% cases [132] and can last up to 3-6 weeks [133], leading to disturbances in salivary secretion, which significantly increase the risk of chronic inflammations [134]. Irrespective of the reason, administration of preparations containing turmeric ingredients may result in the reduction of the oral mucositis symptoms or its complete elimination [135]. In many cases, the efficiency is higher as compared to the commonly used preparations containing synthetic compounds, i.e., chlorhexidine. In order to confirm the therapeutic activity of curcumin toward oral mucositis induced by head and neck cancer treatment, [PERSON] et al. performed a meta-analysis of six randomized controlled trials [136]. The tested formulations included topical gels [137], mouthwashes [138], turmeric extract capsules [139] and nanomicelles [140]. General conclusions indicated that independent of the cancer type and treatment technique, curcumin had the potential to reduce the incidence of severe mucositis and accelerate total recovery. The authors noticed that the efficiency was mostly related to anti-inflammatory activity. However, they pointed out that the curcumin mechanism of action is not entirely explained so far. [PERSON] et al. conducted a study on the tolerance of an oral rinse containing turmeric extract and curcumin. The test group consisted of pediatric oncology patients undergoing therapy with doxorubicin. The patients used a mouthwash with curcumin in addition to the standard rinse containing 0.2% chlorhexidine. Very good tolerance of the rinse by patients and no side effects of its use in the oral cavity have been observed. Some patients experienced a decrease in the symptoms of existing mucositis, while others developed it to a milder state. Additionally, the rinse was easy to use and easy to prepare at home [141]. Another study, presented by [PERSON] et al. in a group of patients undergoing radio-chemotherapy, aimed at comparing the effectiveness of a standard rinse (0.2% chlorhexidine solution) with a 0.004% curcumin solution. The advantages of curcumin over chlorhexidine in the treatment and its better acceptance by patients have been shown. Moreover, in the control group, 40% of patients developed a fungal infection, while no infection was observed in the study group using the curcumin mouthwash [142]. [PERSON] et al. [143] presented a randomized clinical trial involving patients with head and neck cancers also suffering from oral mucositis related to cancer treatment. The patients were divided into three groups receiving curcumin mouthwash, oral curcuminoids in the form of a capsule with nanomicelles or placebo mouthwash. The results indicate that both topical and oral formulations with curcumin significantly decreased oral mucositis symptoms when compared to placebo. It is noteworthy that, at the end of the study, about 33% of the patients treated with curcumin-loaded mouthwash and about 15% of the patients receiving oral capsules had no ulcers, while in the placebo group all patients still had inflammatory symptoms. Similar conclusions have been made by [PERSON] et al. [144] who compared the effectiveness of curcumin-loaded gel, mucosamin oral spray and chlorhexidine mouthrinse in the treatment of chemotherapy-induced oral mucositis.