# Natural Photosensitizers in Clinical Trials
## 3 Natural Photosensitizers in Clinical Trials
### Curcumin in Clinical Trials of Photodynamic Therapy  
Curcumin is the most clinically studied natural photosensitizer. We located seven clinical studies involving PDT with this compound. All of the studies focused on the antimicrobial capabilities of PDT. Five of them tested the ability of CUR-PDT to disinfect the oral cavity, one to disinfect root canal dentin, and one to treat acne. None of the studies reported serious side effects of CUR-PDT, underscoring the reported safety of naturally derived photosensizers. In these papers describing various specific indications, different therapeutic regimens were tested. In a randomized, controlled clinical trial, [PERSON] et al. tested PDT with curcumin for the treatment of stomatitis in patients who are heavy smokers. Their work used a 5 \(\mu\)g/mL solution of CUR I light with a wavelength range between 440 and 460 nm. Six sessions of PDT of dentures and the oral cavity were carried out, three times a week for half a month on each participant. A statistically significant decrease in mean CUR/mL _Candida_ scores from the denture surface and palal mucosa was observed at 6-week follow-up compared to baseline and at the 12-week follow-up compared to the value at 6-week follow-up, while with nystatin therapy and PDT with synthetic PS rose bengal, a decrease was observed only at the 6-week follow-up [35]. [PERSON] et al. conducted a randomized controlled trial examining the effects of photodynamic therapy with blue light and curcumin as an oral disinfect rinse. The CUR-PDT group used a mouthwash with 20 mL of a 30 mg/L CUR solution for 5 min, after which it was removed, and blue light at 455 \(\pm\) 30 nm was introduced to activate curcumin for 5 min. The PDT group showed a significant reduction in CFUs (1 log reduction) after treatment, after 1 h and after 2 h, compared to the pretreatment instance and to the light-only or CUR-only treatment group [36]. [PERSON] et al. also evaluated CUR-PDT as an oral decontamination agent. Patients rinsed their mouths with 15 mL of curcumin solution at concentrations of 25 mg/L and 100 mg/L for 1 min three times each. The mouth was then irradiated for 6 min with 450 nm light. The results indicate that microflora reduction was more effective at a CUR concentration of 100 mg/L. Moreover, unlike the synthetic PS photogem also studied in this work, CUR-PDT showed a reduction in microbial counts not only immediately after the applied treatment, but also after 24 h [37]. [PERSON] et al. investigated oral decontamination of orthodontic patients with CUR-PDT and CUR-PDT combined with sodium dodecyl sulfate (SDS). Patients rinsed their mouths with a 1 mg/L CUR solution or this solution with the addition of a 0.1% SDS solution for 2 min. Then, the buccal and lingual surfaces of the teeth were successively irradiated for 3 min each with light of 450 \(\pm\) 10 nm. Tested immediately after irradiation, the reduction in S. mutans in saliva was from 6.33 \(\pm\) 0.92 to 5.78 \(\pm\) 0.96 log 10 CFU/mL for the CUR-PDT group and from 5.44 \(\pm\) 0.94 to 3.83 \(\pm\) 0.71 log 10 CFU/mL for CUR-PDT + SDS [38]. [PERSON] et al. also tested the utility of CUR-PDT but in combination with photobiomodulation (PBM-T) in oncology patients with mucositis. Patients rinsed their mouths with 20 mL of 1.5 g/L curcumin solution for 5 min. The oral surface was then irradiated for 5 min with light at a wavelength of 468 nm. This was followed by a PBM-T protocol using a low-intensity laser. Of the 14 patients who received PBM-T + PDT, 12 achieved complete healing of the oral cavity, with healing lasting an average of 12 days. Four patients had no signs of inflammation at the final follow-up; two patients had recurrence of otitis media of (OM) (one after an additional cycle of chemotherapy and the other due to [PERSON]'s syndrome);five patients died, and five were not followed up. No treatment-related adverse events occurred in either group [39]. [PERSON] et al.