## 5 Topical Curcumin-Based Formulations in Oral Diseases
### Periodontal Disease
In vitro antimicrobial studies revealed that it was sensitive to curcumin incorporated in the investigated nanoparticles in the concentration range 6.25-50 \(\upmu\)g/mL which is promising in terms of potential application in periodontal disease. Another study involving nanoparticles was presented by [PERSON] et al. [125] who investigated the efficacy of curcumin-loaded PLGA nanoparticles injected directly to the gingival tissues affected with inflammatory condition. The study was performed with the use of an animal model involving rats with artificially induced periodontitis. It was shown that local curcumin delivery resulted with the inhibition of inflammatory bone resorption. However, in order to evaluate the clinical efficacy of the analyzed formulation, further studies testing the local absorption of the active ingredient are required. Direct formulation administration was also described by [PERSON] et al. [126], who developed and investigated the efficacy of curcumin-loaded in situ-forming gels designed to be administered to periodontal pockets. For the obtained formulations the physicochemical properties, i.e. gelation temperature, pH, viscosity, syringeability and stability, were evaluated. Moreover, the drug release was tested in an in vitro experiment, and clinical studies with volunteers suffering from periodontal disease were performed. It was found that the gelation temperature of the analyzed formulations ranged from 28 to 34 \({}^{\circ}\)C which is above room temperature and below body temperature. In this way, the product can be administered with a syringe as liquid which provides excellent condition for periodontal pockets penetration. The gelation process occurs upon the contact with physiological conditions, and due to the viscosity increase, the active ingredient can be released from the carrier in a prolonged manner, without the risk of leakage. Curcumin release mechanism followed zero order kinetics. In the clinical tests, the volunteers were divided into two groups, one of them receiving standard scaling and root planing treatment, and the other one treated additionally with topical in situ gel. It is noteworthy that the curcumin-loaded formulation was well accepted by the patients. The application of the additional curcumin-based preparation resulted with reduced bleeding and reduced periodontal probing depth. The differences in both parameters confirm the efficacy of the applied therapeutic approach and the reduction of inflammation. Another adjunct therapy applied with root scaling and planing was described by [PERSON] et al. [127] who investigated the efficacy of curcumin-loaded topical gel. The study was based on an animal model, and the effects observed in the group treated with standard therapy accompanied with curcumin were compared to those obtained for the group treated with tetracycline instead of curcumin and groups without any adjunct treatment, as well as positive and negative controls. In order to check the outcomes of the study, inflammatory markers, collagen fiber deposition and iron levels were checked. In both groups treated with adjunct therapies, inflammatory processes and bone resorption were significantly reduced when compared to the group without any additional treatment. The results for both curcumin and tetracycline were similar. Moreover, it was noted that curcumin revealed also additional osteogenesis and healing potential. As curcumin is a subject of extensive investigations regarding its potential application in periodontal disease, and the number of available literature studies is high, some systematic reviews and metanalyses have been also published recently. [PERSON] et al. [128] in their systematic review regarding the efficacy of curcumin as an adjunct therapeutic agent applied in periodontal treatment indicated that the compound revealed anti-inflammatory efficacy reflected in the reduction of gingival index and sulcus bleeding index.