Coacervate-based materials as emerging vehicles for drug delivery

Liquid-liquid phase separation (LLPS) is a fundamental mechanism for organizing intracellular biochemical reactions and mediating cellular responses to environmental cues. Inspired by natural membraneless condensates, coacervate-based materials have recently emerged as versatile platforms for drug delivery. Their ability to efficiently encapsulate diverse cargos and release them in response to external or physiological stimuli makes them highly promising for next-generation therapeutic delivery. Despite rapid progress, systematic understanding and design principles for coacervate-based delivery systems remain limited. A comprehensive elucidation of the intermolecular driving forces and mechanisms governing coacervate formation is therefore essential for their rational engineering. This review summarizes the fundamental principles underlying LLPS, fabrication strategies, and characterization techniques of coacervates, followed by recent advances in their applications for delivering small molecules and biomacromolecules. Finally, we discuss current challenges and future opportunities in developing multifunctional, stimuli-responsive coacervates with tunable physicochemical properties. Overall, this review provides insights into the molecular design of coacervate-based systems and highlights their potential in advancing nanomedicine and overcoming biological barriers in drug delivery.