## 5 Topical Curcumin-Based Formulations in Oral Diseases
### Gingivitis  
Gingivitis is a condition described as an inflammation of gingival soft tissues and can be an initial, reversible stage of periodontal disease. However, at this early stage, the teeth are still attached to gum tissues, and no separation is observed. The inflammation is a result of the presence of bacteria in dental biofilm [157]. An untreated condition may eventually lead to periodontal disease. The most important therapeutic intervention requires the removal of dental deposits, particularly calculus, which cannot be eliminated with brushing, and the dental plaque gathered at the top of it [158]. The proper oral hygiene and inhibition of bacterial growth are crucial factors in restoring healthy gums and preventing further progression of periodontal disease. For this purpose, mouthwashes containing chlorhexidine and triclosan can be applied. However, it has been reported that these antibacterial agents can cause allergic reactions and teeth discoloration [159]. Due to antimicrobial and anti-inflammatory properties of curcumin, it may be considered as an alternative to commonly applied agents. The available literature studies presented in this paragraph aimed at the efficacy comparison between curcumin-based formulations and other agents. Figure 5: Antitumor effects of nanoparticles (PLGA NPs), free gefitinib/ Curcumin combination (Free Gef/Cur) and coated nanoparticles (\(\gamma\)-PGA-Gef/Cur NPs) on SAS cell xenograft mice studies. Twenty male athymic BALB/c nu/nu mice were subcutaneously injected with SAS cells (1 \(\times\) 107 cells/mouse) into one flank of each mouse. All animals were randomly divided into four groups (\(n\) = 5). Each animal was intraperitoneally injected with DMSO (control), PLGA NPs, free Cur/Gef or \(\gamma\)-PGA-Gef/Cur NPs every 2 days until the 22 nd day. At the end of the experiment, all animals were anesthetized and sacrificed, and tumors were removed, photographed (**A**) and weighed (**B**). Data represent mean \(\pm\) S.D. ; \(p\) < 0.05 was a significant difference between drug/nanoparticle-treated and control groups. Reproduced from [156] with permission. For example, [PERSON] and [PERSON] [160] analyzed the efficacy of three marketed gels containing standardized turmeric rhizome extract (10 mg/g), 1% chlorhexidine and 0.25% chlorhexidine combined with 1% metronidazoleze. The study involved 60 volunteers divided into three groups. All patients were subjected to mechanical teeth scaling and polishing. The gels were tested for the ability to inhibit the development of inflammation. As responses, the levels of IL-1B and chemokine (C-C motif) ligand 28 (CCL28) were tested. Moreover, clinical parameters including bleeding, gingival index and plaque index were checked. After 29 days of the study, it was shown that the formulations with curcumin and with combined metronidazoleze and chlorhexidine performed better compared to chlorhexidine alone. Moreover, the efficacy of turmeric-based product was slightly better compared to the metronidazoleze and chlorhexidine-based one. The obtained results indicate that curcumin could be potentially useful in the treatment of gingivitis. A similar study comparing the effects of curcumin-loaded gels to the reference product containing 0.2% chlorhexidine gluconate was performed by [PERSON] et al. [161]. In both groups receiving turmeric-derived product and the reference, bleeding, gingival index and plaque index were evaluated. It was shown that both treatments were effective, even though chlorhexidine gel performed better in terms of anti-plaque and anti-inflammatory properties. [PERSON] et al. [162] compared the effects of curcumin-loaded mouthwash with a chlorhexidine-based one on gingival inflammation. No statistically significant differences were shown between the groups using the turmeric-based product and the reference. Both mouthwashes were similar in terms of gingival and plaque indices.