Controlled Interfacial Polymer Self-Assembly Coordinates Ultrahigh Drug Loading and Zero-Order Release in Particles...

Area of Science:

• Biomaterials Engineering
• Drug Delivery Systems
• Nanotechnology

Background:

• Protein-based therapeutics require advanced delivery systems for stability and controlled release.
• Poor miscibility of proteins with traditional carrier materials limits encapsulation efficiency.
• Achieving zero-order release kinetics is crucial for sustained therapeutic effects, particularly in chronic conditions.

Purpose of the Study:

• To engineer polymer-based microparticles for ultrahigh drug loading of protein payloads.
• To achieve zero-order release kinetics for sustained protein delivery.
• To demonstrate efficient glycemic control in type 1 diabetes using these engineered microparticles.

Main Methods:

• Controlled interfacial self-assembly of polymers to create microparticles.
• Transformation of protein molecules into nanoparticles coated with polymers.
• Enhancement of polymer density at the oil-water interface to form a compact shell.
• Utilizing continuous flow engineering for process control and reproducibility.

Main Results:

• Superior encapsulation efficiency of protein nanoparticles, up to 99.9%.
• Microparticles achieved a high protein mass fraction of up to 49.9%.
• Demonstrated in vivo zero-order release kinetics of protein payloads.
• Successful and efficient glycemic control in a type 1 diabetes model.
• High batch-to-batch reproducibility and scale-up feasibility due to continuous flow processing.

Conclusions:

• Engineered microparticles effectively address protein miscibility challenges for enhanced drug loading.
• The developed system provides precise control over protein release kinetics, achieving zero-order profiles.
• This technology offers a promising platform for sustained protein delivery and improved management of type 1 diabetes.