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Highly Bioactive SDF-1α Delivery from Low-Melting-Point, Biodegradable Polymer Microspheres.
Dimitra A Louka1, Nathan Holwell1, Brandon H Thomas1
1Department of Chemical Engineering, Queen's University, Kingston, Ontario K7L 3N6, Canada.
ACS Biomaterials Science & Engineering
|January 12, 2021
Summary
New biodegradable microspheres overcome protein denaturation and inflammation issues common in controlled drug delivery. These novel PEG-(PCG)2 copolymers offer sustained release of therapeutic proteins like stromal-derived factor-1α (SDF-1α) with high bioactivity.
Area of Science:
- Biomaterials Science
- Polymer Chemistry
- Drug Delivery Systems
Background:
- Aliphatic polyester microspheres are used for controlled protein delivery but cause protein denaturation and inflammation.
- Acidic degradation products and high modulus of existing microspheres limit their therapeutic potential.
Purpose of the Study:
- To develop novel low-melting-point poly(ε-caprolactone-co-glycolide)-b-poly(ethylene glycol)-b-poly(ε-caprolactone-co-glycolide) (PEG-(PCG)2) copolymers.
- To evaluate their efficacy in controlled and sustained release of bioactive stromal-derived factor-1α (SDF-1α).
Main Methods:
- Synthesis and characterization of PEG-(PCG)2 triblock copolymers with tunable thermal properties.
- Preparation of microspheres and in vitro degradation studies.
- Assessment of SDF-1α release kinetics and bioactivity retention.
Main Results:
- Microspheres exhibited complete degradation within 8 weeks in vitro with minimal pH change.
- Sustained release of SDF-1α was achieved.
- High bioactivity of the released SDF-1α was maintained.
Conclusions:
- PEG-(PCG)2 copolymers offer a promising alternative to conventional polyester microspheres for protein delivery.
- These novel materials mitigate acidic degradation and inflammatory responses.
- They enable sustained release of bioactive therapeutic proteins for minimally invasive applications.
