Delivery of neuroactive molecules from biodegradable microspheres

grantor: University of TorontoThe defining characteristic of traumatic central nervous system injury is the inability of damaged axons to repair themselves or regenerate. Delivery of neurotrophic factors for example, may enhance axonal nerve regeneration after spinal cord injury. The aim of this project is to encapsulate and deliver neuroactive molecules, such as nerve growth factor (NGF), from biodegradable polymeric microspheres. Biodegradable polymeric microspheres were prepared from poly(lactide-co-glycolide) 50/50 (PLGA50/50), PLGA85/15, poly($\varepsilon$-caprolactone) (PCL) and a blend of PLGA50/50, the latter of which enabled the degradation rate to be tailored. Proteins (i.e. NGF and ovalbumin) were successfully encapsulated into biodegradable polymeric microspheres by the solvent evaporation technique. The release profile ovalbumin was followed by ultraviolet-visible spectrophotometry (UV-vis) and that of NGF by the NGF-enzyme linked immunosorbent assay (ELISA). The degradation profiles of polymer microspheres were followed by changes in molecular weight, morphology and mass loss. PLGA50/50 showed the fastest degradation followed by PLGA85/15 and the blend, with PCL showing the slowest degradation. Ovalbumin, having the similar molecular weight to that of NGF, was encapsulated as a model drug for nerve growth factor in release study. The data obtained from both release and degradation studies suggested that protein release from PLGA50/50 was mainly due to degradation of polymer matrix whereas protein release from PCL was mainly due to the interconnected pore structures. The bioactivity of released NGF was assessed by adrenal rat pheochromacytoma (PC12) cell culture for up to 90 d. Results showed that after 90 d, released NGF maintained its bioactivity to induce neurite outgrowth.M.A.Sc