## 5 Topical Curcumin-Based Formulations in Oral Diseases
### Oral Mucositis and Mouth Ulcers
In a double-blind randomized study, they demonstrated that all three approaches were effective. However, the application of curcumin led to faster recovery. Curcumin has also been considered as a potential therapeutic agent in recurrent aphthous stomatitis (RAS), a condition affecting about 20% of the population [145]. The disease has an unclear etiology and is characterized by the recurrent occurrence of single or multiple small painful ulcers surrounded by erythemat halo in oral mucosa. [PERSON] et al. [146] investigated the efficacy of 1% curcumin nanomicelle gel and 2% curcumin gel in the treatment of RAS in a double-blind clinical trial involving 48 patients. The aim of the study was to compare the conventional topical gel and nanoformulation with the same active ingredient. It was shown that in the case of nanomicelle-based treatment, pain and lesion size reduction was better when compared to the conventional gel. However, in the presented study, only two groups were analyzed, and no control group was applied. Therefore, the general efficacy of curcumin-based treatments cannot be evaluated in this study. On the other hand, there are also other studies and systematic reviews summarizing the current knowledge on this subject. [PERSON] et al. [147] compared the efficacy of curcumin-loaded Orabase(r) paste and the conventional therapy with triacmionolone acetonide. The study showed no statistically significant differences in pain severity and lesion diameter observed in both therapeutic approaches. The obtained results demonstrate that curcumin can be considered as an effective therapeutic agent in the patients with corticosteroids contraindications. [PERSON] et al. [148] in their systematic review summarized eight clinical studies evaluating the efficacy of curcumin in RAS treatment and concluded that curcumin displays generally promising properties as a therapeutic agent decreasing pain and lesions diameter. It was shown that its efficacy was comparable to commonly accepted steroid-based therapy. In the studies involving placebo groups, superior effects were reported in the patients treated with curcumin. Many studies indicate that compounds present in turmeric reveal potential against pathogenic microorganisms and thus contribute to the reduction of the inflammatory symptoms. However, it should be emphasized that using plant raw material may not provide the expected antibacterial effect, as it was described by [PERSON] et al. The authors prepared a mouthwash from store-bought turmeric and used it against bacterial cultures taken form the oral cavity of volunteers. The results showed no apparent antibacterial and bacteriostatic activity. Moreover, some signs of bacterial growth promotion were even noticed [149]. Therefore, most of the current works describe formulations containing pure curcumin. The studies prepared by [PERSON] et al. described the development of nanocarriers for improved delivery of curcumin in the treatment of bacterial or fungal infections in the oral cavity. The drug loaded into solid lipid nanoparticles showed greater stability and efficacy in neutralizing _Staphylococcus_ sp. or _Candida albicans_[150]. The predicted positive therapeutic effect was also attributed to good mucoadhesive properties of the tested formulations ex vivo. [PERSON] et al. also pointed out the importance of mucoadhesion in relation to the topical efficacy of curcumin-containing formulations. The authors designed and developed zein/beta cyclodextrin mucoadhesive nanoparticles for buccal delivery of curcumin in the form of sprayable suspension. The ex vivo tests on porcine buccal mucosa showed superior resistance toward washing out and indicated great potential in local delivery of the drug [151]. Another studies presented by [PERSON] et al. concerned the curcumin-based photodynamic antibacterial therapy against oral mucositis in oncological patients. The drug was applied in the form of spray into the oral cavity and the tissue was further illuminated with blue light to achieve the phototoxic effect.