Targeted drug delivery system to neural cells utilizes the nicotinic acetylcholine receptor

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Abstract

Drug delivery to the brain is still a major challenge in the field of therapeutics, especially for large and hydrophilic compounds. In order to achieve drug delivery of therapeutic concentration in the central nervous system, the problematic blood brain barrier (BBB) must be overcome. This work presents the formulation of a targeted nanoparticle-based drug delivery system using a specific neural cell targeting ligand, rabies virus derived peptide (RDP). Characterization studies revealed that RDP could be conjugated to drug-loaded PLGA nanoparticles of average diameter 257.10 ± 22.39 nm and zeta potential of -5.51 ± 0.73 mV. In vitro studies showed that addition of RDP to nanoparticles enhanced drug accumulation in a neural cell line specifically as opposed to non-neural cell lines. It was revealed that this drug delivery system is reliant upon nicotinic acetylcholine receptor (nAChR) function for RDP-facilitated effects, supporting a cellular uptake mechanism of action. The specific neural cell targeting capabilities of RDP via the nAChR offers a non-toxic, non-invasive and promising approach to the delivery of therapeutics to the brain.
Original languageEnglish
Pages (from-to)12-20
Number of pages8
JournalInternational Journal of Pharmaceutics
Volume525
Issue number1
Early online date12 Apr 2017
DOIs
Publication statusPublished - 15 Jun 2017

Keywords

  • Drug delivery system
  • rabies virus
  • targeted nanoparticles
  • neural
  • blood brain barrier (BBB)
  • nicotinic acetylcholine receptor

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