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

Abstract 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.