title: Local Delivery of Neurotrophin-3 and Anti-NogoA Promotes Repair After Spinal Cord Injury.
abstract: Tissue and functional repair after spinal cord injury (SCI) continue to elude researchers. Neurotrophin-3 (NT-3) and anti-NogoA have been shown to promote axonal regeneration in animal models of SCI; however, localized and sustained delivery to the central nervous system (CNS) remains a critical challenge for these and other macromolecular therapeutics. An injectable drug delivery system (DDS) has previously been developed, which can provide safe local delivery to the spinal cord. This DDS, composed of poly(lactic-co-glycolic acid) (PLGA) nanoparticles (nps) dispersed in a hyaluronan methylcellulose hydrogel, was adapted for the tunable bioactive delivery of NT-3 and anti-NogoA. Furthermore, the combined delivery of NT-3 and anti-NogoA from the DDS in an impact/compression model of SCI increases axon density and improves locomotor function. The benefits of this np/hydrogel DDS observed for NT-3 and anti-NogoA demonstrate the utility of the DDS as a local delivery strategy for protein therapeutics to the CNS.
authors.affiliation: 1 Department of Chemical Engineering and Applied Chemistry, University of Toronto , Toronto, Canada .|2 Institute of Biomaterials and Biomedical Engineering, University of Toronto , Toronto, Canada .
authors.forename: Irja
authors.initials: I
authors.lastname: Elliott Donaghue
authors.affiliation: 3 Division of Genetics and Development, Toronto Western Research Institute, University of Toronto , Toronto, Canada .|4 Krembil Neuroscience Centre, Toronto Western Hospital, University Health Network , Toronto, Canada .|5 Division of Neurosurgery, Department of Surgery, University of Toronto , Toronto, Canada .
authors.forename: Charles H
authors.initials: CH
authors.lastname: Tator
authors.affiliation: 1 Department of Chemical Engineering and Applied Chemistry, University of Toronto , Toronto, Canada .|2 Institute of Biomaterials and Biomedical Engineering, University of Toronto , Toronto, Canada .|6 Donnelly Centre for Cellular & Biomolecular Research, University of Toronto, Toronto, Canada .
authors.forename: Molly S
authors.initials: MS
authors.lastname: Shoichet
mesh_terms: D000818:Animals; D000906:Antibodies / Q000494:pharmacology*; D004195:Disease Models, Animal; D004337:Drug Carriers / Q000494:pharmacology*; D005260:Female; D020933:Neurotrophin 3 / Q000494:pharmacology*; D000070798:Nogo Proteins / Q000037:antagonists & inhibitors*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013117:Spinal Cord Compression / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D013119:Spinal Cord Injuries / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D058630:Spinal Cord Regeneration / Q000187:drug effects*
chemical_list: D000906:Antibodies; D004337:Drug Carriers; D020933:Neurotrophin 3; D000070798:Nogo Proteins