Design of core-shell gel beads for time-programmed protein release

Area of Science:

• Biomaterials Science
• Drug Delivery Systems
• Polymer Chemistry

Background:

• Alginate gel beads are widely used for drug encapsulation.
• Controlling the release rate of macromolecular drugs from hydrogels is challenging.
• Existing alginate formulations may exhibit rapid drug release, limiting therapeutic efficacy.

Purpose of the Study:

• To develop modified calcium alginate gel beads for controlled release of macromolecular drugs.
• To investigate the effect of poly(γ-glutamate) (γ-PGA) coating on drug release kinetics.
• To enhance the onset release time and modulate drug release profiles.

Main Methods:

• Coating calcium alginate gel beads with calcium poly(γ-glutamate) (Ca-γ-PGA).
• Modifying γ-PGA with alkyl groups (e.g., butyl groups) to alter hydrophobicity.
• Evaluating the release of dextran and proteins (albumin, IgG, fibrinogen) from coated beads.
• Analyzing the effect of bead size and polymer modification on release onset time.

Main Results:

• γ-PGA coating significantly increased the onset release time of dextran from 13 min (bare beads) to 49 min.
• Hydrophobic modification of γ-PGA with 20 mol % butyl groups further extended onset release time to 87 min.
• Protein release (albumin, IgG, fibrinogen) exhibited S-shaped curves with onset release times dependent on molecular weight and conformation.
• Modified alginate beads maintained injectable diameters.

Conclusions:

• Modified alginate gel beads with γ-PGA or its alkylates effectively modulate macromolecular drug release onset.
• Hydrophobic polymer coatings enhance the lag time for drug release, improving control.
• The developed system shows promise for injectable drug delivery systems with tunable release profiles.