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Intrathecal delivery of a polymeric nanocomposite hydrogel after spinal cord injury

Paper ID Volume ID Publish Year Pages File Format Full-Text
7725 562 2010 9 PDF Available
Title
Intrathecal delivery of a polymeric nanocomposite hydrogel after spinal cord injury
Abstract

Major traumatic spinal cord injury (SCI) results in permanent paralysis below the site of injury. The effectiveness of systemically delivered pharmacological therapies against SCI can be limited by the blood–spinal cord barrier and side effects. Local drug delivery to the injured spinal cord can be achieved using a minimally invasive biopolymer matrix of hyaluronan and methylcellulose injected into the intrathecal space, bypassing the blood–spinal cord barrier and overcoming limitations of existing strategies. Composite hydrogels of drug-loaded poly(lactide-co-glycolide) (PLGA) nanoparticles dispersed in this biopolymer matrix meet the in vitro design criteria for prolonged local release. Using a blank (without drug) composite designed for 28-day sustained release, we presently explore the mechanism of particle-mediated hydrogel stabilization in vitro and aspects of biocompatibility and safety in vivo. The composite hydrogel is well tolerated in the intrathecal space of spinal cord injured rats, showing no increase in inflammation, scarring, or cavity volume relative to controls, and no significant effect on locomotor function up to 28 days. Furthermore, there was no effect on locomotor function in healthy animals which received the composite hydrogel, although a qualitative increase in ED-1 staining was apparent. These data support the further development of composite hydrogels of hyaluronan and methylcellulose containing PLGA nanoparticles for sustained local delivery to the injured spinal cord, an application for which there are no approved alternatives.

Keywords
Spinal cord injury; Drug delivery; Hydrogel; Nanoparticles; Hyaluronan; Methylcellulose
First Page Preview
Intrathecal delivery of a polymeric nanocomposite hydrogel after spinal cord injury
Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 31, Issue 30, October 2010, Pages 7631–7639
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering