UCIBIO, REQUINTE, Laboratory of Pharmaceutical Technology, Centre of Research in Pharmaceutical Sciences, Faculty of Pharmacy, University of Porto, Porto, Portugal.
CNC - Center for Neuroscience and Cell Biology, Faculty of Medicine (Pólo I), University of Coimbra, Coimbra, Portugal; FFUC - Faculty of Pharmacy, Pólo das Ciências da Saúde, University of Coimbra, Coimbra, Portugal.
J Control Release. 2019 Feb 10;295:187-200. doi: 10.1016/j.jconrel.2018.12.049. Epub 2019 Jan 2.
Epileptic seizures and anxiety crisis are severe conditions that require fast and effective treatment, targeting the brain. Current emergency antiepiletics and anxiolytics have limited brain bioavailability, following oral, intravenous or rectal administration. This relates with the limited extent at which these drugs bypass the blood brain barrier (BBB). Thereby, the development of strategies that significantly improve the brain bioavailability of these drugs, along with a simple and safe administration by patients, attenuating and/or preventing epileptic seizures or anxiety crisis, are still a major need. In this respect, the nasal/intranasal route has been suggested as a promising strategy for drug targeting to the brain, thus avoiding the BBB. Besides, the use of lipid-based nanosystems, such as solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC), liposomes, nanoemulsions and microemulsions, have been demonstrating high efficiency for nose-to-brain transport. This review highlights the potential of using lipid-based nanosystems in the management of epilepsy and anxiety, by means of the nasal/intranasal route. So far, the reported studies have shown promising results, being required more in vivo experiments to further advance for clinical trials. Furthermore, toxicological concerns related to the need of evaluate the impairment on the mucociliary clearance mechanism have been pointed.
癫痫发作和焦虑危机是严重的情况,需要快速有效的治疗,针对大脑。目前,口服、静脉或直肠给药的紧急抗癫痫药和抗焦虑药的脑生物利用度有限。这与这些药物通过血脑屏障(BBB)的程度有限有关。因此,开发能显著提高这些药物脑生物利用度的策略,同时使患者能够简单、安全地给药,减轻和/或预防癫痫发作或焦虑危机,仍然是一个主要需求。在这方面,鼻内/鼻腔给药途径已被认为是一种有前途的靶向大脑的药物策略,从而避免了 BBB。此外,使用基于脂质的纳米系统,如固体脂质纳米粒(SLN)和纳米结构脂质载体(NLC)、脂质体、纳米乳液和微乳液,已被证明在鼻内/鼻腔给药途径中具有很高的脑内传递效率。这篇综述强调了通过鼻内/鼻腔途径使用基于脂质的纳米系统来管理癫痫和焦虑的潜力。到目前为止,已有的研究报告显示出了有希望的结果,需要进行更多的体内实验来进一步推进临床试验。此外,还指出了与需要评估对黏液纤毛清除机制的损害有关的毒理学问题。