Nanoprecipitation-Induced Formation of Nanoparticles for Drug Delivery

Nanoprecipitation has become one of the most widely used methods for fabricating drug delivery nanoparticles, owing to its simplicity, reproducibility, and compatibility with diverse therapeutic cargos. Based on the principle of solvent displacement, it provides a mild and energy-efficient approach for producing nanoparticles with tunable size, morphology, and encapsulation efficiency (EE%). Over the past three decades, nanoprecipitation has been applied to polymers, lipids, proteins, and inorganic carriers, establishing it as a versatile platform across nanomedicine. Recent advances in microfluidic systems and impingement jet mixing have overcome many of the limitations of conventional laboratory-scale methods by enabling sub-millisecond mixing, improved reproducibility, and scalability to good manufacturing practice (GMP) manufacturing. These innovations not only enhance control over critical quality attributes, including particle size distribution and drug loading, but also accelerate the clinical translation of nanoparticle formulations. In this review, we summarize the fundamental principles and mechanistic insights of nanoprecipitation with emphasis on clinically relevant biodegradable materials. We further highlight recent developments that extend its applications from hydrophobic drugs to nucleic acids, illustrate the transition from small-scale research to advanced GMP manufacturing, and explore future opportunities for integrating modeling, automation, and quality by design approaches to advance nanoprecipitation in drug delivery.