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Encapsulation and stabilization of nerve growth factor into poly(lactic-co-glycolic) acid microspheres
X M Lam1, E T Duenas, J L Cleland
1Department of Pharmaceutical Research and Development, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA. lam.xanthe@gene.com
Journal of Pharmaceutical Sciences
|December 18, 2001
Summary
Researchers developed a stable, sustained-release formulation for recombinant human nerve growth factor (rhNGF) using zinc complexation and poly(lactic-co-glycolic) acid (PLGA) microspheres, enabling 14-day controlled release for neuronal disease treatment.
Area of Science:
- Biomaterials Science
- Drug Delivery Systems
- Neuroscience
Background:
- Recombinant human nerve growth factor (rhNGF) holds therapeutic potential for neuronal diseases.
- Achieving stable, sustained release of rhNGF has been a significant challenge.
- Previous attempts using common excipients led to protein aggregation during release.
Purpose of the Study:
- To develop a stable, sustained-release formulation of rhNGF.
- To overcome protein degradation during microencapsulation and in vitro release.
- To achieve controlled release of rhNGF for potential neuronal disease therapy.
Main Methods:
- rhNGF was encapsulated into poly(lactic-co-glycolic) acid (PLGA) microspheres via spray freeze-drying.
- An insoluble rhNGF-zinc complex was formed prior to encapsulation to enhance stability.
- Zinc carbonate was incorporated into the polymer phase to control release kinetics.
Main Results:
- The rhNGF-zinc complex formation significantly stabilized the protein during microencapsulation and release.
- A formulation using 10% rhNGF in 12 kDa PLGA (50:50) achieved 14 days of continuous release.
- Addition of zinc carbonate resulted in a low initial burst (approx. 1%) and controlled release rate.
Conclusions:
- Zinc complexation is an effective strategy to stabilize rhNGF in PLGA microspheres.
- The developed formulation provides sustained release of rhNGF for 14 days.
- This approach offers a promising method for delivering rhNGF for neuronal disease treatment.