经鼻腔给药制剂治疗癫痫急症的研究进展。

A review of intranasal formulations for the treatment of seizure emergencies.

机构信息

Department of Pharmaceutics, University of Minnesota, Minneapolis, MN, USA.

Department of Experimental and Clinical Pharmacology, University of Minnesota, Minneapolis, MN, USA; Department of Neurology, University of Minnesota, Minneapolis, MN, USA.

出版信息

J Control Release. 2016 Sep 10;237:147-59. doi: 10.1016/j.jconrel.2016.07.001. Epub 2016 Jul 7.

DOI:10.1016/j.jconrel.2016.07.001

PMID:27397490

Abstract

Epileptic seizure emergencies are life-threatening conditions, which in their most severe form, status epilepticus, have a high mortality rate if not quickly terminated. Treatment requires rapid delivery of anti-epileptics such as benzodiazepines to the brain. The nasal route is attractive due to its non-invasiveness, potential for direct nose to brain delivery, high vascularity, relatively large absorptive surface area, and avoidance of intestinal/liver metabolism. However, the limited volume of the nasal cavity and poor water solubility of anti-epileptics restrict absorption, leading to insufficient therapeutic brain levels. This review covers various formulation approaches adopted to improve nasal delivery of drugs, especially benzodiazepines, used to treat seizure emergencies. Other general topics such as nasal anatomy, challenges to nasal delivery, and drug/formulation considerations for nose to brain delivery are also discussed.

摘要

癫痫发作急症是危及生命的病症，如果不能迅速终止，最严重的形式癫痫持续状态的死亡率很高。治疗需要迅速将苯二氮䓬类等抗癫痫药物递送到脑部。由于经鼻途径是非侵入性的，具有直接将药物递送到脑部的潜力，血管丰富，相对较大的吸收表面积，并且可以避免肠道/肝脏代谢，因此具有吸引力。然而，鼻腔的容积有限，以及抗癫痫药物的水溶性差，限制了吸收，导致脑部的治疗水平不足。本综述涵盖了为改善用于治疗急症发作的药物（特别是苯二氮䓬类药物）的经鼻递送来采用的各种制剂方法。还讨论了其他一般主题，如鼻解剖结构、经鼻递药的挑战以及用于脑内递药的药物/制剂考虑因素。