Issue 1, 2015

Sustained delivery of bioactive neurotrophin-3 to the injured spinal cord

Abstract

Spinal cord injury is a debilitating condition that currently lacks effective clinical treatment. Neurotrophin-3 (NT-3) has been demonstrated in experimental animal models to induce axonal regeneration and functional improvements, yet its local delivery remains challenging. For ultimate clinical translation, a drug delivery system is required for localized, sustained, and minimally invasive release. Here, an injectable composite drug delivery system (DDS) composed of biodegradable polymeric nanoparticles dispersed in a hyaluronan/methyl cellulose hydrogel was injected into the intrathecal space to achieve acute local delivery to the spinal cord after a thoracic clip compression injury. NT-3 was encapsulated in the DDS and released in vitro for up to 50 d. With a single injection of the DDS into the intrathecal space of the injured spinal cord, NT-3 diffused ventrally through the cord and was detectable in the spinal cord for at least 28 d therein. Delivery of NT-3 resulted in significant axon growth with no effect on the astroglial response to injury in comparison with vehicle and injury controls. NT-3 treatment promoted functional improvements at 21 d according to the Basso Beattie Bresnahan locomotor scale in comparison with the DDS alone. The sustained delivery of bioactive NT-3 to the injured spinal cord achieved in this study demonstrates the promise of this DDS for central nervous system repair.

Graphical abstract: Sustained delivery of bioactive neurotrophin-3 to the injured spinal cord

Supplementary files

Article information

Article type
Paper
Submitted
21 Aug 2014
Accepted
03 Sep 2014
First published
12 Sep 2014

Biomater. Sci., 2015,3, 65-72

Sustained delivery of bioactive neurotrophin-3 to the injured spinal cord

I. Elliott Donaghue, C. H. Tator and M. S. Shoichet, Biomater. Sci., 2015, 3, 65 DOI: 10.1039/C4BM00311J

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