Glutaryl Melatonin Niosome Gel for Topical Oral Mucositis: Anti- Inflammatory and Anticandidiasis

Author(s): Teerasak Damrongrungruang*, Panjaree Panpitakkul, Jirachaya Somudorn, Pimpitchaya Sangchart, Pramote Mahakunakorn, Prangtip Uthaiwat, Jureerut Daduang, Panyada Panyatip, Ploenthip Puthongking, Aroonsri Priprem

Journal Name: Current Drug Delivery

Volume 17 , Issue 3 , 2020


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Graphical Abstract:


Abstract:

Background: Glutaryl melatonin, which is synthesized from melatonin and is a pineal glandderived 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.

Methods: 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 oilinduced 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 from 1 μM of nystatin (p = 0.05). Nitric oxide, interleukin-6 and tumor necrosis factors 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 weight 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 were 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.

Keywords: Glutaryl melatonin, anti-candidiasis, anti-inflammation, niosome gel, 5-fluorouracil, injections.

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VOLUME: 17
ISSUE: 3
Year: 2020
Page: [195 - 206]
Pages: 12
DOI: 10.2174/1567201817666200122162545
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