Modulation of protein release from penta-block copolymer microspheres

Area of Science:

• Biomaterials Science
• Polymer Chemistry
• Drug Delivery

Background:

• Achieving zero-order protein release without denaturation from degrading polymeric microparticles is difficult.
• Poly(lactic-co-glycolic acid)-poly(ethylene oxide)-poly(lactic-co-glycolic acid) (PLGA-PEO-PLGA) penta-block copolymers offer potential for controlled release.

Purpose of the Study:

• To develop protein-loaded microspheres using novel PLGA-PEO-PLGA penta-block copolymers for linear sustained protein release.
• To investigate the influence of PLGA segment molecular weight on microsphere properties and protein release kinetics.

Main Methods:

• Lysozyme-loaded microspheres (40 µm) were prepared using solid-in-oil-in-water solvent extraction/evaporation.
• Two penta-block copolymers with different PLGA molecular weights (20 kDa and 40 kDa) were synthesized.
• Polymer blending and microsphere mixing strategies were evaluated for controlled release.

Main Results:

• Microspheres exhibited similar size and encapsulation efficiency (50-60%) but varied porosities.
• 50P40-MS showed linear but incomplete release; 50P20-MS showed non-linear but complete release.
• A 1:1 mixture of microspheres achieved a biphasic release: initial burst (13%) followed by nearly complete linear release over 8 weeks.

Conclusions:

• The PEO block mass ratio in PLGA-PEO-PLGA copolymers significantly impacts glass transition temperature (Tg), microsphere structure, and release behavior at 37°C.
• A 1:1 microsphere mixture provides a promising strategy for achieving sustained, linear protein release, tunable for specific applications.