Marttin E, Verhoef J C, Romeijn S G, Merkus F W
Division of Pharmaceutical Technology and Biopharmaceutics, Leiden/Amsterdam Center for Drug Research, Leiden University, The Netherlands.
Pharm Res. 1995 Aug;12(8):1151-7. doi: 10.1023/a:1016207809199.
The assessment of the effects of nasal absorption enhancers on the rat nasal epithelium and membrane permeability in vivo after a single nasal dose of the enhancers.
The release of marker compounds (protein, cholesterol and acid phosphatase) from the nasal epithelium was measured using a lavage technique. The nasal membrane permeability was determined after intravenous administration of a systemic tracer (FITC-albumin).
The effects of the absorption enhancers could be classified into four categories. The first consisted of HP beta CD (5%), DM beta CD (2%) and RAMEB (2%) and was not different from the control (physiological saline). For the second category, DM beta CD (5%), effects were significantly higher than for the control. The third category, SGC (1%), was more active than DM beta CD (5%) but less active than the last group. The fourth, most membrane damaging, category consisted of STDHF (1%), laureth-9 (1%) and LPC (1%). Administration of these three enhancers also resulted in release of acid phosphatase, indicating that severe membrane damage occurred. The release of cholesterol from nasal epithelium was largely dependent on the cholesterol solubilisation of the absorption enhancers. The amount of cholesterol released by laureth-9 and LPC was the largest.
The results of this in vivo study are in agreement (i.e. similarity in rank order) with morphological and ciliotoxicity studies of nasal absorption enhancers, demonstrating that this in vivo model is a valuable tool to classify nasal absorption enhancers according to their effects on the rat nasal epithelium.
评估单次经鼻给予鼻腔吸收促进剂后，其对大鼠鼻上皮及膜通透性的体内效应。
采用灌洗技术测定标记化合物（蛋白质、胆固醇和酸性磷酸酶）从鼻上皮的释放情况。静脉注射全身示踪剂（异硫氰酸荧光素标记的白蛋白）后测定鼻黏膜通透性。
吸收促进剂的效应可分为四类。第一类包括羟丙基-β-环糊精（5%）、二甲基-β-环糊精（2%）和随机甲基化-β-环糊精（2%），与对照组（生理盐水）无差异。第二类，二甲基-β-环糊精（5%），效应显著高于对照组。第三类，司盘80（1%），比二甲基-β-环糊精（5%）更具活性，但比最后一组活性低。第四类，也是对膜损伤最大的一类，包括十四烷基二甲基苄基氯化铵（1%）、月桂醇聚醚-9（1%）和溶血磷脂酰胆碱（1%）。给予这三种促进剂也导致酸性磷酸酶释放，表明发生了严重的膜损伤。鼻上皮中胆固醇的释放很大程度上取决于吸收促进剂对胆固醇的增溶作用。月桂醇聚醚-9和溶血磷脂酰胆碱释放的胆固醇量最大。
本体内研究结果与鼻腔吸收促进剂的形态学和纤毛毒性研究结果一致（即排序相似），表明该体内模型是根据其对大鼠鼻上皮的作用对鼻腔吸收促进剂进行分类的有价值工具。
