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06:34
Validation of Therapeutic Agent Conjugation to Polyvinyl Alcohol-Coated Medical Devices
Published on: November 29, 2024
Sustained release of bioactive therapeutic proteins from a biodegradable elastomeric device
Frank Gu1, Ronald Neufeld, Brian Amsden
1Department of Chemical Engineering, Queen's University, Kingston, Ontario, Canada K7L 3N6.
Summary
This study developed a biodegradable cylindrical device for sustained, localized protein delivery. The device successfully released therapeutic proteins like VEGF, IFN-γ, and IL-2 at constant rates with high bioactivity, demonstrating its potential.
Area of Science:
- Biomaterials Science
- Drug Delivery Systems
- Regenerative Medicine
Background:
- Effective localized delivery of therapeutic proteins necessitates biodegradable devices for sustained release within a therapeutic window.
- Achieving constant release rates and maintaining protein bioactivity are critical challenges in protein-based therapies.
Purpose of the Study:
- To demonstrate the feasibility of a biodegradable elastomeric device in a cylindrical geometry for sustained protein release.
- To evaluate the release kinetics and bioactivity of various therapeutic proteins delivered from this device.
Main Methods:
- Preparation of cylindrical elastomeric devices via photo-cross-linking of acrylated star-poly(epsilon-caprolactone-co-d,l-lactide) macromer.
- Entrapment of vascular endothelial growth factor (VEGF), interferon-gamma (IFN-γ), and interleukin-2 (IL-2) within the elastomer matrix.
- Assessment of protein release rates and cell-based bioactivity assays.
Main Results:
- Proteins were released at a nearly constant rate (zero-order kinetics) for 70-80% of the release profile, irrespective of protein type.
- Decreasing macromer molecular weight increased release rate but maintained zero-order kinetics.
- Interleukin-2 (IL-2) and Interferon-gamma (IFN-γ) exhibited high bioactivity (>80% bioactive), while Vascular Endothelial Growth Factor (VEGF) showed lower bioactivity (57% bioactive).
Conclusions:
- Biodegradable cylindrical elastomeric devices can achieve sustained, zero-order release of therapeutic proteins.
- The formulation demonstrates potential for localized, controlled delivery of bioactive proteins.
- Further optimization may be needed to enhance the bioactivity of certain released proteins, such as VEGF.
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