Peptide-functionalized polymeric nanoparticles for active targeting of damaged tissue in animals with experimental autoimmune encephalomyelitis

Neurosci Lett. 2015 Aug 18:602:126-32. doi: 10.1016/j.neulet.2015.06.049. Epub 2015 Jun 30.

Abstract

Increased permeability of blood vessels is an indicator for various injuries and diseases, including multiple sclerosis (MS), of the central nervous system. Nanoparticles have the potential to deliver drugs locally to sites of tissue damage, reducing the drug administered and limiting associated side effects, but efficient accumulation still remains a challenge. We developed peptide-functionalized polymeric nanoparticles to target blood clots and the extracellular matrix molecule nidogen, which are associated with areas of tissue damage. Using the induction of experimental autoimmune encephalomyelitis in rats to provide a model of MS associated with tissue damage and blood vessel lesions, all targeted nanoparticles were delivered systemically. In vivo data demonstrates enhanced accumulation of peptide functionalized nanoparticles at the injury site compared to scrambled and naive controls, particularly for nanoparticles functionalized to target fibrin clots. This suggests that further investigations with drug laden, peptide functionalized nanoparticles might be of particular interest in the development of treatment strategies for MS.

Keywords: Multiple sclerosis; Nanoparticles; Spinal cord; Targeted delivery.

Publication types

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

MeSH terms

  • Animals
  • Carbocyanines / administration & dosage
  • Carbocyanines / chemistry
  • Drug Carriers
  • Encephalomyelitis, Autoimmune, Experimental / drug therapy*
  • Encephalomyelitis, Autoimmune, Experimental / metabolism
  • Female
  • Fibrin / chemistry
  • Fibrin / metabolism
  • Fluorescent Dyes / administration & dosage
  • Fluorescent Dyes / chemistry
  • Hydrophobic and Hydrophilic Interactions
  • Lactones / chemistry
  • Laminin / chemistry
  • Membrane Glycoproteins / metabolism
  • Multiple Sclerosis / drug therapy
  • Multiple Sclerosis / metabolism
  • Nanoparticles
  • Oligopeptides / administration & dosage*
  • Oligopeptides / chemistry
  • Polyethylene Glycols / chemistry
  • Rats
  • Rats, Inbred F344
  • Spinal Cord / drug effects
  • Spinal Cord / metabolism
  • Up-Regulation

Substances

  • 1,1'-dioleyl-3,3,3',3'-tetramethylindocarbocyanine
  • Carbocyanines
  • Drug Carriers
  • Fluorescent Dyes
  • Lactones
  • Laminin
  • Membrane Glycoproteins
  • Oligopeptides
  • nidogen
  • poly(ethylene oxide)-b-poly(caprolactone)
  • Polyethylene Glycols
  • 3,3'-dioctadecyloxacarbocyanine
  • Fibrin