| Neurotrophin-3 (NT-3) and anti-NogoA have shown promise in regenerative strategies after spinal cord injury; however, conventional methods for localized release to the injured spinal cord are either prone to infection or not suitable for sustained release. To address these issues, we have designed a composite drug delivery system that is comprised of poly(lactic-co-glycolic acid) (PLGA) nanoparticles dispersed in an injectable hydrogel of hyaluronan and methyl cellulose (HAMC). Achieving sustained and bioactive protein release from PLGA particles is a known challenge; consequently, we studied the effects of processing parameters and excipient selection on protein release, stability, and bioactivity. We found that embedding PLGA nanoparticles in HAMC results in more linear drug release likely due to the formation of a diffusion-limiting layer of methyl cellulose on the particle surface. Co-encapsulated MgCO3 was able to significantly improve NT-3 bioactivity, while trehalose + hyaluronan was able to improve anti-NogoA bioactivity and release. |
