Preparation and Characterization of Biocompatible Chitosan Nanoparticles for Targeted Brain Delivery of Peptides

Yemisci M., Caban S., Fernandez-Megia E., ÇAPAN Y., Couvreur P., DALKARA T.

NEUROTROPHIC FACTORS: METHODS AND PROTOCOLS, 2ND EDITION, vol.1727, pp.443-454, 2018 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 1727
  • Publication Date: 2018
  • Doi Number: 10.1007/978-1-4939-7571-6_36
  • Journal Name: NEUROTROPHIC FACTORS: METHODS AND PROTOCOLS, 2ND EDITION
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.443-454
  • Keywords: Nanoparticles, Brain drug delivery, Blood-brain barrier, Neurotrophic factors, Caspase inhibitors, Neuroprotection, Chitosan, TRANSFERRIN RECEPTOR, PROTEIN DELIVERY, DRUG-DELIVERY, BARRIER, TRANSPORT, CAPILLARIES, CASPASES, ISCHEMIA, ANTIBODY, DESIGN
  • Lokman Hekim University Affiliated: No

Abstract

Here, we describe a nanocarrier system that can transfer chitosan nanoparticles loaded with either small peptides such as the caspase inhibitor Z-DEVD-FMK or a large peptide like basic fibroblast growth factor across the blood-brain barrier. The nanoparticles are selectively directed to the brain and are not measurably taken up by the liver and spleen. Intravital fluorescent microscopy provides an opportunity to study the penetration kinetics of nanoparticles loaded with fluorescent agents such as Nile red. Nanoparticles functionalized with anti-transferrin antibody and loaded with peptides efficiently provided neuroprotection when systemically administered either as a formulation bearing a single peptide or a mixture of them. Failure of brain permeation of the nanoparticles after inhibition of vesicular transcytosis by imatinib as well as when nanoparticles were not functionalized with anti-transferrin antibody indicates that this nanomedicine formulation is rapidly transported across the blood-brain barrier by receptor-mediated transcytosis.