黄芩苷脂质体、β-环糊精包合物及磷脂复合物鼻黏膜渗透性及毒性研究

The nasal mucosa permeability and toxicity of baicalin carrier systems liposomes,β-cyclodextrin inclusion compound,and phospholipid complex

为提高鼻腔给药后脑内药物浓度,本文探讨了以脂质体、β-环糊精包合物和磷脂复合物为黄芩苷载药体系的体外离体动物鼻黏膜渗透性及鼻腔毒性。采用猪、羊、兔鼻黏膜,以体外扩散池装置进行鼻黏膜渗透实验,HPLC法测定接受池中药物累积渗透量,以表观渗透系数为评价标准,考察脂质体、β-环糊精包合物及磷脂复合物载药系统对黄芩苷在离体动物鼻黏膜的透过性,从而筛选出黄芩苷经鼻给药最佳载药形式;采用在体法考察黄芩苷及其磷脂复合物对蟾蜍上颚黏膜纤毛运动的影响和大鼠鼻黏膜长期毒性。3种黄芩苷载药体系的表观渗透系数均明显高于黄芩苷(P<0.05),滞后时间也比黄芩苷短,提示3种载药载体均可提高黄芩苷的鼻黏膜渗透性,同时磷脂复合物的表观渗透系数明显高于脂质体和环糊精包合物,表明黄芩苷磷脂复合物鼻黏膜渗透性明显优于另外两种载药体系(P<0.05)。黄芩苷磷脂复合物对纤毛运动无影响,对大鼠鼻黏膜也无明显刺激性。结果表明,磷脂复合物为黄芩苷经鼻给药最佳载药形式,能明显提高其鼻黏膜渗透性,对鼻黏膜无毒性,可用于鼻腔给药。

To increase drug concentration in the head through intranasal administration, we have investigated the excised animal nasal mucosa permeability and nasal toxicity of the baicalin drug carrier systems, such as baicalin liposomes, β-cyclodextrin inclusion compound, and phospholipid complex. A transport of baicalin drug carrier systems through nasal mucosa was simulated in diffusion chamber in vitro, and swine, caprine and rabbit nasal mucosa was used, The concentration of drug in the receptor was determined by HPLC. By taking the apparent permeability coefficients as evaluation standard, investigated the isolated animal nasal mucosa permeability of different baicalin drug systems was investigated for screening the best baicalin drug carrier system through nasal cavity administration. Toxicity of baicalin and its phospholipids complex on toad palate mucosal cilia movement and rats nasal mucosa long-term toxicity were studied in vivo. The apparent perme-ability coefficient of three kinds of baicalin drug carrier systems was better than that of baicalin （P 〈 0.05）, and its lag-time was obviously shortened. At the same time, the apparent permeability coefficient of phospholipid complex was higher than those of other two drug carrier systems （P 〈 0.05）. The results showed that the baicalin phospholipids complex nasal mucosa permeability was obviously superior to the other two drug systems. Baicalin phospholipids complex had no toxicity to ciliary movement, and had no irritation to rat nasal mucosa.The results show that baicalin phospholipid complex was the best baicalin drug carrier system, it could signifi-cantly enhance the permeability of baicalin across nasal mucosa, had no toxicity to nasal mucosa, and could be used for intranasal administration.