Abstract
[Display omitted]
•Leaky blood vessels accompany many CNS pathologies, including multiple sclerosis.•Fibrinogen and nidogen are progressively up-regulated after disease onset.•Targeted delivery can reduce “off-target” effects.•Peptide modified polymeric nanoparticles can target blood clots and ECM molecules.•Fibrin targeting nanoparticles demonstrate increased binding to lesion sites.
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.
