以青稞β-葡聚糖为基质的白藜芦醇鼻用凝胶剂研究

Development of Resveratrol Nasal Gel Using Tibetan Hulless Barley β-glucan as a Matrix

目的:探索以青稞β-葡聚糖为基质的白藜芦醇鼻用凝胶剂的给药性能、体外释放及渗透鼻黏膜的性能。方法:通过考察pH、黏度、凝胶强度、持水性和黏膜黏附性来评价该凝胶剂鼻腔给药的适用性,用特制的鼻腔给药装置考察给药方便性,按《中国药典》法测定体外释放度,用猪鼻黏膜按Frantz扩散池法测定对鼻黏膜的渗透性,并用多个药物释放数学模型探讨该凝胶剂的体外释放和渗透鼻黏膜的机制。结果:凝胶强度和黏度等参数的测定结果表明该凝胶剂具有柔软、易涂展、持水性好、黏度大但呈假塑性流动、黏附性好、pH与鼻腔pH相近等特点;体外试验8 h,累积释放度和渗透猪鼻黏膜累积透过率分别为93.86%,62.46%,释药机制均符合Weibull模型。结论:白藜芦醇青稞β-葡聚糖凝胶剂对鼻腔黏膜有很好的相容性,并具有良好的黏附和释药性能,用特制鼻腔给药装置可实现给药方便性。

Objective：Tibetan hulless barley β-glucan（THBG） is a natural bioadhesive material.The present study was aimed at developing a THBG-based mucoadhesive gel of resveratrol,a potential cancer therapeutic agent richly obtained from the roots of Polyclonum cuspidatum and some other traditional Chinese medicines with low oral bioavailability,for nasal systemic delivery.Method：A 2% resveratrol nasal gel was prepared with 4% THBG as a matrix and 1% menthol as a penetrant,and characterized in terms of its physical properties（including pH,viscosity,gel strength,water holding capacity and mucoadhesion）,in vitro cumulative release and in vitro transmucosal cumulative delivery in porcine olfactorymucosa.The administration convenience of a specially designed controllable nasal injector and mucosa irritancy of the selected gel were also evaluated in healthy volunteers.Result：The nasal gel was found to exhibit pseudoplastic rheology with properties of high viscosity,low gel strength,high water holding capacity,strong mucoadhesion,good spreadability,easy administration and no irritation.The percents of cumulative release in vitro and transmucosal cumulative delivery in vitro at 8h were 93.86% and 62.46% respectively,and the drug release behavior in two tests were observed to fit the Weibull distribution model well.Conclusion：The results demonstrated that the THBG-based nasal gel of resveratrol is a patient-friendly dosage form with desirable bioadhesion,distribution,and release performance,and the THBG is suitable for using as the matrix of mucoadhesive preparations.