A NANOGEL-BASED DRUG DELIVERY SYSTEM FOR OLIGODENDROCYTE PRESERVATION IN SPINAL CORD INJURY

Spinal cord injury (SCI) induces inflammation, oxidative stress, and demyelination, leading to oligodendrocyte loss and limited functional recovery. The aim of this study was to develop a biocompatible nanogel-based drug delivery system to modulate the post-injury microenvironment and preserve the oligodendroglial component. A PEG–Jeffamine polymeric nanogel was synthesized. Among the tested strategies, one carbohydrate-functionalized nanogel showed a promising shift of uptake toward oligodendrocytes, suggesting a potential route to enhance oligodendroglial engagement. The nanogel was physicochemically characterized and tested in mixed primary mouse spinal cord cultures containing neurons, astrocytes, microglia, and oligodendrocytes. Biocompatibility, inflammatory inertness, and cellular uptake were evaluated under basal and inflammatory conditions. The nanogel was well tolerated at selected concentrations. Uptake analyses showed internalization by all major cell populations, with a pronounced association with oligodendrocytes. Under oxidative stress, nanogel-mediated delivery of atorvastatin reduced apoptosis and improved oligodendrocyte survival, consistent with enhanced intracellular availability. Taken together, these results identify the PEG–Jeffamine nanogel as a biocompatible platform for local drug delivery in SCI, with carbohydrate functionalization enabling oligodendrocyte-specific therapies in SCI and other disorders affecting these cells.