Modified polymeric nanoparticles for neuronal drug delivery

Abstract

The development of effective drug delivery systems for neurons is an urgent and necessary need. In this project, biodegradable nanoparticles (PEG-PCL) are decorated with a tetra peptide (IKRG) on the surface. This sequence was reported previously to mimic BDNF (Brain-derived neurotrophic factor) and target TrkB receptors that are present in abundance in neurons. The cellular uptake for nanoparticles with and without BDNF peptides (IKRG) was first evaluated in cell lines with and without TrkB receptors respectively. Enhanced uptake for targeting nanoparticles was observed in TrkB positive PC12 cell but not in TrkB negative HeLa cells. The modified nanoparticles were internalized into primary cultured dorsal root ganglion (DRG) neurons and the cellular uptake was significantly higher than particles without peptide modification. PTEN (Phophatase and tension homolog deleted on chromosome 10) is one of the regulators of neuron regeneration ability in peripheral and central nervous systems. Its inhibition promotes axonal outgrowth of injured neurons. In this study, PTEN-inhibitor (VO-OHpic) was encapsulated into the modified nanoparticles and released sustainably over 14 days. The increased uptake and sustainable release resulted in prolonged drug effect in DRG, which was confirmed by the analysis of the expression of pAKT that is involved in PTEN downstream signal. The DRGs viability was well-preserved by nanoparticles with encapsulated drug compared to free drug. Our findings suggest that the BDNF peptide modified PEG-PCL nanoparticles are promising carriers for localized drug delivery to neurons.

Date of Award	2017
Original language	English
Awarding Institution	The Hong Kong University of Science and Technology