Nose-to-brain delivery of lipid-based nanosystems for epileptic seizures and anxiety crisis

J Control Release. 2019 Feb 10:295:187-200. doi: 10.1016/j.jconrel.2018.12.049. Epub 2019 Jan 2.

Abstract

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.

Keywords: Antiepileptics; Anxiety; Anxiolytics; Epilepsy; Lipid-based nanosystems; Nasal/intranasal route.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Administration, Intranasal
  • Animals
  • Anti-Anxiety Agents / administration & dosage*
  • Anti-Anxiety Agents / pharmacokinetics
  • Anti-Anxiety Agents / therapeutic use
  • Anticonvulsants / administration & dosage*
  • Anticonvulsants / pharmacokinetics
  • Anticonvulsants / therapeutic use
  • Anxiety / drug therapy*
  • Anxiety / metabolism
  • Brain / drug effects
  • Brain / metabolism*
  • Drug Delivery Systems* / methods
  • Emulsions / chemistry
  • Emulsions / metabolism
  • Humans
  • Lipid Metabolism
  • Lipids / chemistry
  • Liposomes / chemistry
  • Liposomes / metabolism
  • Nanoparticles / chemistry
  • Nanoparticles / metabolism
  • Seizures / drug therapy*
  • Seizures / metabolism

Substances

  • Anti-Anxiety Agents
  • Anticonvulsants
  • Emulsions
  • Lipids
  • Liposomes