Minimally invasive nasal infusion (MINI) approach for CNS delivery of protein therapeutics: A case study with ovalbumin

J Control Release. 2024 Aug:372:674-681. doi: 10.1016/j.jconrel.2024.06.056. Epub 2024 Jul 1.

Abstract

One of the primary obstacles in treating central nervous system (CNS) disorders lies in the limited ability of disease-modifying drugs to cross the blood-brain barrier (BBB). Our previously described Minimally Invasive Nasal Depot (MIND) technique has proven successful in delivering various drugs to the brain in rat models via a trans-olfactory mucosal approach. In this study, we introduce a novel Minimally Invasive Nasal Infusion (MINI) delivery approach for administering ovalbumin, a model protein, utilizing a programmable infusion pump (iPRECIO SMP-310R) in a mouse model. This research highlights the significant role of olfactory mucosa in nose-to-brain delivery, with an efficacy of nearly 45% compared to intracerebroventricular (ICV) administration. This demonstrates its potential as an alternative procedure for treating CNS diseases, offering a greater safety profile relative to the highly invasive clinical routes traditionally adopted for CNS drug delivery.

Keywords: CNS delivery; Microfluidic infusion system; Neurodegenerative diseases; Nose-to-brain delivery; Protein therapeutics.

MeSH terms

  • Administration, Intranasal*
  • Animals
  • Blood-Brain Barrier / metabolism
  • Brain / metabolism
  • Drug Delivery Systems
  • Infusion Pumps
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Ovalbumin* / administration & dosage

Substances

  • Ovalbumin