Triggered drug release from dynamic microspheres via a protein conformational change

Area of Science:

• Biomaterials Science
• Drug Delivery Systems
• Protein Engineering

Background:

• Hydrogel microspheres are widely used for drug encapsulation and delivery.
• Controlling the release rate and ensuring drug integrity post-release are significant challenges in hydrogel-based therapies.

Purpose of the Study:

• To engineer dynamic hydrogel microspheres utilizing protein conformational changes for controlled drug release.
• To investigate the precise volume changes of microspheres induced by a specific ligand-protein interaction.
• To evaluate the structural integrity of a model drug after release from these responsive hydrogels.

Main Methods:

• Formation and characterization of dynamic hydrogel microspheres.
• Induction of calmodulin protein conformational change using the ligand trifluoperazine.
• Quantification of microsphere volume changes (48.7% decrease).
• Encapsulation and triggered release of vascular endothelial growth factor (VEGF) as a model drug.
• Assessment of VEGF native conformation post-release (85.6 +/- 10.5%).

Main Results:

• A 48.7% reduction in microsphere volume was achieved by ligand-induced calmodulin conformational change.
• Controlled, pre-determined release of vascular endothelial growth factor (VEGF) was successfully triggered.
• The released VEGF largely retained its native conformation, indicating minimal denaturation.

Conclusions:

• Protein conformational changes can effectively control volume dynamics in hydrogel microspheres.
• This approach offers a novel mechanism for precise, on-demand drug release.
• The method preserves the structural integrity of encapsulated biologics, enhancing therapeutic potential.