A Library of Polyphenol‐Amino Acid Condensates for High‐Throughput Continuous Flow Production of Nanomedicines with Ultra‐High Drug Loading

Synthesizing high drug-loading nanomedicines remains a formidable challenge, and achieving universally applicable, continuous, large-scale engineered production of such nanomedicines presents even greater difficulties. This study presents a scalable library of polyphenol-amino acid condensates. By selecting amino acids, the library enables precise customization of key properties, such as carrier capacity, bioactivity, and other critical attributes, offering a versatile range of options for various application scenarios. Leveraging the properties of solvent-mediated disassembly and reassembly of condensates achieved an ultra-high drug loading of 86% for paclitaxel. For a range of poorly soluble molecules, the drug loading capacity exceeded 50%, indicating broad applicability. Furthermore, employing a continuous microfluidic device, the production rate can reach 5 mL min^-1 (36 g per day), with the nanoparticle size precisely tunable and a polydispersity index (PDI) below 0.2. The polyphenol-based carrier demonstrates efficient cellular uptake and, in three distinct animal models, has been shown to enhance the therapeutic efficacy of paclitaxel without significant side effects. This study presents a streamlined, efficient, and scalable approach using microfluidics to produce nanomedicines with ultra-high drug loading, offering a promising strategy for the nanoformulation of poorly soluble drugs.