药物经鼻-脑转运的离体牛嗅黏膜模型及体内外相关性

Excised Bovine Olfactory Mucosa Model to Study Nose-Brain Transport of Drugs and the in vivo-in vitro Correlation

分离牛嗅黏膜,以石杉碱甲和盐酸锥双净为模型药物,用Franz扩散池,建立评价药物经鼻-脑转运的体外模型。通过测定药物透牛嗅黏膜的累积扩散率,考察药物亲脂性、浓度、pH、剂型和促透剂对其透黏膜扩散的影响,并通过测定鼻腔给药后大鼠脑脊液的药物浓度评价本模型的体内外相关性。结果表明药物透牛嗅黏膜转运以被动扩散为主,亲脂性是影响扩散的关键因素。药物透牛嗅黏膜累积扩散率与大鼠脑脊液药时曲线下面积线性相关。本研究建立的离体牛嗅黏膜模型实验手段简便,适用于经鼻脑靶向给药系统的体外评价。

The in vitro model to study the direct nose-brain transport of drugs was built by using excised bovine olfactory mucosa and Franz diffusion chamber, with huperzine A and trybizine hydrochloride as the model drugs. By determining the transmucosal cumulative diffusion rates, the influences of the drug lipophilicity, concentration, pH, dosage forms and transmucosal enhancers on their diffusion extents were investigated. The concentrations of the drugs in the cerebrospinal fluid were measured after intran＇asal administration of the two model drugs to rats, in order to evaluate their in vivo-in vitro correlations. The results showed that the major mechanism of drug transport was the passive diffusion and the drug lipophilicity was a critical factor. The transmucosal cumulative diffusion rates correlated well to their A UCCSF in rats： The in vitro model would be useful for the evaluation of the intranasal delivery system for brain targeting.