Dhawan Neha, Kumar Krishan, Kalia A N, Arora Saahil
Department of Pharmaceutics/ Department of Pharmacognosy, ISF College of Pharmacy, Moga- 142001 (Punjab) India.
Curr Drug Deliv. 2014;11(3):415-25. doi: 10.2174/1567201810666131129110756.
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.
口腔黏膜炎是癌症化疗（发生率为30 - 76%）和放疗（发生率超过50%）的主要副作用之一。目前口腔黏膜炎的姑息治疗方法包括使用如培非明、血小板衍生因子等特殊药物或口腔卫生用品，但这些方法存在各种缺点，如全身副作用、由于颊黏膜快速清除导致效果不佳、患者不友好的给药系统以及仅仅是症状缓解。在本研究中，制备了微乳化丁香酚、蜂蜜和透明质酸钠的N - 琥珀酰壳聚糖凝胶给药系统，以探究它们对口腔黏膜炎各种病理因素的多重和协同作用。N - 琥珀酰壳聚糖在我们实验室合成，并负载微乳化丁香酚（10% v/v）、蜂蜜（10% v/v）和透明质酸钠（0.2% w/v），以制备具有最佳pH值、铺展性、黏膜黏附强度和黏度的凝胶剂。在PBS（pH - 6.4）中8小时后，N - 琥珀酰壳聚糖凝胶中丁香酚的体外释放率为87.45±0.14%，与壳聚糖凝胶相比释放效果更好。使用大鼠颊黏膜组织进行的体外渗透研究还表明，与壳聚糖凝胶相比，丁香酚通过N - 琥珀酰壳聚糖的外排通量更好，增强比（ER）为1.71。与基于壳聚糖的凝胶剂以及市售洗必泰制剂相比，基于N - 琥珀酰壳聚糖的凝胶剂对金黄色葡萄球菌和白色念珠菌的抗菌效果在统计学上显著更高（p<0.05）。在5 - 氟尿嘧啶诱导的口腔黏膜炎动物（Wistar大鼠）模型中，N - 琥珀酰壳聚糖凝胶剂在15天内比壳聚糖凝胶制剂显示出更高的存活率、体重增加和高组织再生活性。与疾病对照组相比，该制剂成功提高了动物口腔黏膜的存活率并减轻了炎症（p<0.05），因此表明N - 琥珀酰壳聚糖凝胶剂在治疗口腔黏膜炎方面具有潜力。
