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.
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