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Delivering neuroactive molecules from biodegradable microspheres for application in central nervous system disorders
1Department of Chemical Engineering and Applied Chemistry, University of Toronto, Ontario, Canada.
Biomaterials
|February 27, 1999
Summary
Biodegradable microspheres were developed to control the release of nerve growth factor (NGF) for potential spinal cord injury repair. These microspheres maintained NGF bioactivity for 91 days, offering a promising therapeutic delivery system.
Area of Science:
- Biomaterials Science
- Neuroscience
- Regenerative Medicine
Background:
- Nerve growth factor (NGF) shows potential for enhancing axonal regeneration after central nervous system (CNS) injuries, including spinal cord injury.
- Controlled drug delivery systems are crucial for sustained therapeutic effects in CNS repair.
- Biodegradable polymeric microspheres offer a promising platform for localized and sustained delivery of neurotrophic factors.
Purpose of the Study:
- To tailor the release profile of NGF from biodegradable polymeric microspheres.
- To investigate the influence of polymer composition and protein loading on NGF release kinetics.
- To evaluate the long-term bioactivity of NGF released from these microspheres.
Main Methods:
- Microspheres were fabricated using poly(lactic-co-glycolic acid) (PLGA 50/50, PLGA 85/15), polycaprolactone (PCL), and a PCL/PLGA 50/50 blend.
- Varying protein loading amounts were incorporated into the microspheres.
- NGF release was monitored over 91 days using NGF-ELISA, and bioactivity was assessed with PC12 cells.
Main Results:
- A two-phase release profile was observed, characterized by an initial burst release and a subsequent sustained release phase driven by polymer degradation.
- Polymer degradation significantly influenced release, particularly for PLGA 50/50 and PLGA 85/15 formulations.
- NGF demonstrated sustained bioactivity for the entire 91-day study period, exceeding previously reported durations.
Conclusions:
- Biodegradable polymeric microspheres can effectively control NGF release, providing sustained bioactivity for extended periods.
- The choice of polymer and protein loading can be optimized to modulate NGF release kinetics for potential therapeutic applications.
- This controlled delivery system holds promise for enhancing axonal regeneration in CNS injuries like spinal cord injury.