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Drug carriers in medicine embrace a complex subset of tasks calling for multifunctionality. Here, the synthesisof pro\u2010drug\u2010loaded core cross\u2010linked polymeric micelles (CCPMs) in a continuous flow processis reported, which combines the commonly separated steps of micelle formation, core cross\u2010linking, functionalization, and purification into a single process. Redox\u2010responsive CCPMs are formed from thiol\u2010reactive polypept(o)ides of polysarcosine\u2010<jats:italic>block<\/jats:italic>\u2010poly(<jats:italic>S<\/jats:italic>\u2010ethylsulfonyl\u2010<jats:sc>l<\/jats:sc>\u2010cysteine) and functional cross\u2010linkers based on dihydrolipoic acid hydrazide for pH\u2010dependent release of paclitaxel. The precisely controlled microfluidic process allows the production of spherical micelles (<jats:italic>D<\/jats:italic><jats:sub>h<\/jats:sub>\u00a0= 35\u00a0nm) with low polydispersity values (PDI &lt; 0.1) while avoiding toxic organic solvents and additives with unfavorable safety profiles. Self\u2010assembly and cross\u2010linking via slit interdigital micromixers produces 350\u2013700\u00a0mg of CCPMs\/h per single system, while purification by online tangential flow filtration successfully removes impurities (unimer \u2264 0.5%). The formed paclitaxel\u2010loaded CCPMs possess the desired pH\u2010responsive release profile, display stable drug encapsulation, an improved toxicity profile compared to Abraxane (a trademark of Bristol\u2010Myers Squibb), and therapeutic efficiency in the B16F1\u2010xenotransplanted zebrafish model. The combination of reactive polymers, functional cross\u2010linkers, and microfluidics enables the continuous\u2010flow synthesis of therapeutically active CCPMs in a single process.<\/jats:p>","DOI":"10.1002\/adma.202210704","type":"journal-article","created":{"date-parts":[[2023,3,19]],"date-time":"2023-03-19T00:44:12Z","timestamp":1679186652000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Complex Structures Made Simple \u2013 Continuous Flow Production of Core Cross\u2010Linked Polymeric Micelles for Paclitaxel Pro\u2010Drug\u2010Delivery"],"prefix":"10.1002","volume":"35","author":[{"given":"Tobias A.","family":"Bauer","sequence":"first","affiliation":[{"name":"Leiden Academic Centre for Drug Research (LACDR) Leiden University  Einsteinweg 55 Leiden 2333CC The 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