Efficient Cholera Toxin B Subunit-Based Nanoparticles with MRI Capability for Drug Delivery to the Brain Following Intranasal Administration

Macromol Biosci. 2019 Feb;19(2):e1800340. doi: 10.1002/mabi.201800340. Epub 2018 Dec 7.

Abstract

Alzheimer's disease (AD) is an incurable neurodegenerative brain disorder that exhibits clear pathologic changes in the hippocampus. Traditional drug delivery systems are ineffective due to the existence of the blood-brain barrier (BBB). In this study, an efficient, stable, and easily constructed nanosystem (CB-Gd-Cy5.5) based on the cholera toxin B subunit (CB) is designed to improve the efficiency of drug delivery to the brain, especially the hippocampus. Through intranasal administration, CB-Gd-Cy5.5 is easily delivered to the brain without intervention by the BBB. The CB in CB-Gd-Cy5.5 is used for specifically combining with the monosialoganglioside GM1, which is widely found in the hippocampus. This nanosystem exhibits impressive performance in accumulating in the hippocampus. In addition, the good magnetic resonance imaging (MRI) capability of CB-Gd-Cy5.5 can satisfy the monitoring of AD in the different stages.

Keywords: blood-brain barrier; brain drug delivery; cholera toxin B subunit; intranasal administration; magnetic resonance imaging.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Intranasal
  • Alzheimer Disease / drug therapy*
  • Animals
  • Blood-Brain Barrier
  • Carbocyanines
  • Cell Line
  • Cholera Toxin / chemistry
  • Cholera Toxin / pharmacology*
  • Drug Carriers / chemistry
  • Drug Carriers / pharmacology*
  • G(M1) Ganglioside / administration & dosage
  • G(M1) Ganglioside / chemistry*
  • Hippocampus / physiology*
  • Magnetic Resonance Imaging
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Nanoparticles / administration & dosage
  • Nanoparticles / chemistry*

Substances

  • CY5.5 cyanine dye
  • Carbocyanines
  • Drug Carriers
  • G(M1) Ganglioside
  • Cholera Toxin