Polymeric nanoparticle system to target activated microglia/macrophages in spinal cord injury

J Control Release. 2014 Jan 28:174:15-26. doi: 10.1016/j.jconrel.2013.11.001. Epub 2013 Nov 10.

Abstract

The possibility to control the fate of the cells responsible for secondary mechanisms following spinal cord injury (SCI) is one of the most relevant challenges to reduce the post traumatic degeneration of the spinal cord. In particular, microglia/macrophages associated inflammation appears to be a self-propelling mechanism which leads to progressive neurodegeneration and development of persisting pain state. In this study we analyzed the interactions between poly(methyl methacrylate) nanoparticles (PMMA-NPs) and microglia/macrophages in vitro and in vivo, characterizing the features that influence their internalization and ability to deliver drugs. The uptake mechanisms of PMMA-NPs were in-depth investigated, together with their possible toxic effects on microglia/macrophages. In addition, the possibility to deliver a mimetic drug within microglia/macrophages was characterized in vitro and in vivo. Drug-loaded polymeric NPs resulted to be a promising tool for the selective administration of pharmacological compounds in activated microglia/macrophages and thus potentially able to counteract relevant secondary inflammatory events in SCI.

Keywords: Drug delivery; Macrophage; Microglia; Nanoparticle; Spinal cord injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Behavior, Animal / drug effects
  • Carbocyanines / administration & dosage
  • Carbocyanines / chemistry
  • Cell Survival / drug effects
  • Cells, Cultured
  • Coloring Agents / administration & dosage
  • Coloring Agents / chemistry
  • Drug Carriers / administration & dosage*
  • Drug Carriers / chemistry
  • Female
  • Hydrogels
  • Lipopolysaccharides
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Microglia / drug effects
  • Microglia / metabolism*
  • Nanoparticles / administration & dosage*
  • Nanoparticles / chemistry
  • Polymethyl Methacrylate / administration & dosage*
  • Polymethyl Methacrylate / chemistry
  • Spinal Cord / metabolism
  • Spinal Cord Injuries / metabolism*

Substances

  • Carbocyanines
  • Coloring Agents
  • Drug Carriers
  • Hydrogels
  • Lipopolysaccharides
  • TO-PRO-3
  • Polymethyl Methacrylate