Glutaryl melatonin niosome gel for topical oral mucositis: anti-inflammatory and anticandidiasis

BACKGROUND: Glutaryl melatonin, which is synthesized from melatonin and is a pineal gland-derived neurohormone with anti-inflammatory and anti-oxidant properties, was comparatively investigated for its potential use as a topical anti-inflammatory agent. OBJECTIVE: Glutaryl melatonin, synthesized and screened for in vitro anti-candidiasis and in vitro and in vivo anti-inflammatory activities, was formulated as a niosome gel for topical oral evaluation in 5-fluorouracil-induced oral mucositis in mice. METHOD: In vitro anti-fungal activity in Candida albicans, in vitro anti-inflammatory activity in Escherichia coli liposaccharide-induced RAW cells and in vivo anti-inflammatory activity using a croton oil-induced ear edema model in ICR mice were investigated. Mucositis in mice (n = 6/group, 10-week-old mice) was induced by intraperitoneal injections of 5-fluorouracil, and the mice were subjected to a topical oral application of niosome gel containing melatonin (2% w/w) or glutaryl melatonin (2% w/w) and were compared with mice subjected to blank, fluocinolone acetonide (0.5% w/w) and control conditions. RESULTS: Glutaryl melatonin, at a 14. 2 mM concentration, showed the highest fungicidal effect on C. albicans using the broth dilution method, indicating a nonsignificant difference for 1 muM of nystatin (p = 0.05). Nitric oxide, interleukin-6 and tumor necrosis factor-alpha were analyzed by ELISA. Liposaccharide-induced RAW cells were significantly reduced by glutaryl melatonin (p < 0.01). Ear edema inhibition of glutaryl melatonin was significant 1 h after application compared with that of melatonin (p = 0.03). Food consumption and body weights of the 5-fluorouracil-treated mice were significantly lower than those of the normal mice before all treatments (p < 0.05). Differences in the amount of licking behavior, which was observed in the control group for 5 min, were noticeable in the 5-fluorouracil-treated mice but not in the mice treated with the glutaryl melatonin niosome gel. CONCLUSION: Glutaryl melatonin exhibited mild anti-candidiasis and anti-inflammatory properties. The incorporation of glutaryl melatonin in a niosome gel formulation, demonstrated the potential for topical oral applications to reduce oral discomfort caused by 5-fluorouracil treatment in mice.