N-Succinyl Chitosan as Buccal Penetration Enhancer for Delivery of Herbal Agents in Treatment of Oral Mucositis
Oral mucositis is one of the major side effects of cancer chemotherapy (30-76%) and radiotherapy (over 50%).
Current palliative treatments of oral mucositis include specialized agents like pelifermin, platelet derived factors etc. or
oral hygienic agents which suffered from various drawbacks like systemic side effect, least effect owing to fast wash out
of buccal mucosa, patient unfriendly delivery systems, and mere symptomatic relief. In this research work, N-succinyl
chitosan gel delivery system of microemulsified eugenol, honey and sodium hyaluronate was prepared to explore their
multiple and synergistic effects on various pathological factors of oral mucositis. N-succinyl chitosan was synthesized in
our laboratory and loaded with microemulsified eugenol (10% v/v), honey (10% v/v) and sodium hyaluronate (0.2% w/v)
to prepare orogel with optimum pH, spreadability, mucoadhesion strength, and viscosity. In vitro eugenol release from
N-succinyl chitosan gel after 8 hours in PBS (pH-6.4) was found to be 87.45±0.14%, which was better in comparison to
that released from chitosan gel. Ex vivo penetration studies using rat buccal mucosal tissue also suggested better J-efflux
of eugenol through N-succinyl chitosan in comparison to chitosan gel with enhancement ratio (ER) of 1.71. The antimicrobial
effect of N-succinyl chitosan based orogel against S. aureus and C. albicans efficacy was found to be statistically high
in comparison to chitosan based orogel as well as marketed formulation of chlorhexidine (p<0.05). The N-succinyl chitosan
orogel in 5-fluoro uracil induced oral mucositis animal (Wistar rats) model showed enhanced survival ratio, weight gain and
high tissue regeneration activity than chitosan gel formulation within 15 days. The formulation was successful in elevating
the survival and reducing the inflammation in the oral mucosa of animals compared to disease control (p<0.05) and hence
suggesting the potential of N-succinyl chitosan orogel in the treatment of oral mucositis.
Keywords: Chemotherapy, chitosan, eugenol, honey, N-succinyl chitosan, sodium hyaluronate.
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