Davis Stanley S, Illum Lisbeth
Institute of Pharmaceutical Sciences, University of Nottingham, Nottingham, UK.
Clin Pharmacokinet. 2003;42(13):1107-28. doi: 10.2165/00003088-200342130-00003.
This paper describes the basic concepts for the transmucosal delivery of drugs, and in particular the use of the nasal route for delivery of challenging drugs such as polar low-molecular-weight drugs and peptides and proteins. Strategies for the exploitation of absorption enhancers for the improvement of nasal delivery are discussed, including consideration of mechanisms of action and the correlation between toxic effect and absorption enhancement. Selected enhancer systems, such as cyclodextrins, phospholipids, bioadhesive powder systems and chitosan, are discussed in detail. Examples of the use of these enhancers in preclinical and clinical studies are given. Methods for assessing irritancy and damage to the nasal membrane from the use of absorption enhancers are also described. Finally, the mucosal use of absorption enhancers (chitosan) for the improved nasal delivery of vaccines is reported with reference to recent phase I/II clinical studies.
本文描述了药物经黏膜给药的基本概念,特别是利用鼻腔途径递送诸如极性低分子量药物以及肽和蛋白质等具有挑战性的药物。讨论了利用吸收促进剂改善鼻腔给药的策略,包括作用机制的考量以及毒性效应与吸收增强之间的相关性。详细讨论了选定的促进剂系统,如环糊精、磷脂、生物黏附性粉末系统和壳聚糖。给出了这些促进剂在临床前和临床研究中的应用实例。还描述了评估吸收促进剂对鼻黏膜刺激性和损伤的方法。最后,参考近期的I/II期临床研究报道了吸收促进剂(壳聚糖)在黏膜方面用于改善疫苗鼻腔给药的情况。