RVG29-modified microRNA-loaded nanoparticles improve ischemic brain injury by nasal delivery

Drug Deliv. 2020 Dec;27(1):772-781. doi: 10.1080/10717544.2020.1760960.

Abstract

Effective nose-to-brain delivery needs to be developed to treat neurodegenerative diseases. Regulating miR-124 can effectively improve the symptoms of ischemic brain injury and provide a certain protective effect from brain damage after cerebral ischemia. We used rat models of middle cerebral artery occlusion (t-MCAO) with ischemic brain injury, and we delivered RVG29-NPs-miR124 intranasally to treat neurological damage after cerebral ischemia. Rhoa and neurological scores in rats treated by intranasal administration of RVG29-PEG-PLGA/miRNA-124 were significantly lower than those in PEG-PLGA/miRNA-124 nasal administration and RVG29-PLGA/miRNA-124 nasal administration group treated rats. These results indicate that the nose-to-brain delivery of PLGA/miRNA-124 conjugated with PEG and RVG29 alleviated the symptoms of cerebral ischemia-reperfusion injury. Thus, nasal delivery of RVG29-PEG-PLGA/miRNA-124 could be a new method for treating neurodegenerative diseases.

Keywords: Ischemic brain injury; Nose-to-brain; RVG29; miRNA.

MeSH terms

  • Administration, Intranasal
  • Animals
  • Brain / drug effects*
  • Brain / metabolism
  • Brain Ischemia / drug therapy*
  • Brain Ischemia / metabolism
  • Disease Models, Animal
  • Drug Carriers / chemistry*
  • GAP-43 Protein / genetics
  • Gene Expression / drug effects
  • Glycoproteins / chemistry*
  • MicroRNAs / administration & dosage*
  • MicroRNAs / pharmacokinetics
  • MicroRNAs / therapeutic use
  • Nanoparticles / chemistry*
  • Particle Size
  • Peptide Fragments / chemistry*
  • Polyesters / chemistry*
  • Polyethylene Glycols / chemistry*
  • Rats, Sprague-Dawley
  • Surface Properties
  • Viral Proteins / chemistry*
  • rho GTP-Binding Proteins / genetics

Substances

  • Drug Carriers
  • GAP-43 Protein
  • Glycoproteins
  • MIRN124 microRNA, rat
  • MicroRNAs
  • Peptide Fragments
  • Polyesters
  • Viral Proteins
  • polyethylene glycol-poly(lactide-co-glycolide)
  • rabies virus glycoprotein peptide
  • Polyethylene Glycols
  • RhoA protein, rat
  • rho GTP-Binding Proteins