Controlled Interfacial Polymer Self-assembly Coordinates Ultrahigh Drug Loading and Zero-Order Release in Particles Prepared under Continuous Flow

Here, we successfully engineer microparticles through controlled interfacial self-assembly of polymers to harmonize ultrahigh drug loading with zero-order release of protein payloads. To address their poor miscibility with carrier materials, protein molecules are transformed into nanoparticles, whose surfaces are covered with polymer molecules. This polymer layer hinders the transfer of cargo nanoparticles from oil to water, achieving superior encapsulation efficiency (up to 99.9%). To control payload release, we enhance the polymer density at the oil-water interface, forming a compact shell for microparticles. The resultant microparticles could harvest up to 49.9% mass fraction of proteins with zero-order release kinetics in vivo, enabling an efficient glycemic control in type 1 diabetes. Moreover, the precise control of engineering process offered through continuous flow results in high batch-to-batch reproducibility and, ultimately, excellent scale-up feasibility.