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This work introduces an enhanced mixing process to overcome these obstacles, specifically aiming to produce consistently sized poly(lactic\u2010co\u2010glycolic) acid (PLGA) nanoparticles loaded with anti\u2010tumor drugs. By innovatively integrating a pulsation dampener into the microfluidic channels of a continuous flow preparation system, the flow stability of piston pumps is improved nearly tenfold. Consequently, large\u2010scale production of uniformly sized nanoparticles with customizable dimensions is achieved through nanoprecipitation. Furthermore, incorporating terminal double\u2010bond\u2010functionalized poly(lactic\u2010co\u2010glycolic acid)\u2010b\u2010poly(ethylene glycol)\u2010maleimide (PLGA\u2010PEG\u2010Mal) enables these nanoparticles to act as nano\u2010crosslinkers. This facilitates in situ crosslinking with thiolated hyaluronic acid via a spontaneous thiol\u2010ene coupling reaction under physiological conditions, allowing for minimally invasive drug administration and significantly enhancing localized drug retention. The material's degradability in the presence of endogenous enzymes ensures controlled drug release, as demonstrated with the anti\u2010tumor drug doxorubicin (DOX). Validation in a murine breast cancer model shows reduced toxicity and a substantial reduction in tumor weight compared to the free DOX group. These findings confirm the approach's effectiveness for breast cancer treatment and pave the way for innovative solutions in nanomedicine, providing a practical microfluidic mixing system for the design and large\u2010scale production of nanomedicines.<\/jats:p>","DOI":"10.1002\/smll.202406521","type":"journal-article","created":{"date-parts":[[2024,10,29]],"date-time":"2024-10-29T06:31:21Z","timestamp":1730183481000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Development of Stable and Intensified Mixing Processes for the Precise and Scalable Production of Uniform Drug Delivery Nanocarriers"],"prefix":"10.1002","volume":"20","author":[{"given":"Meng","family":"Cao","sequence":"first","affiliation":[{"name":"Division of Breast Surgery, Department of General Surgery, Nanjing Drum Tower Hospital, the Affiliated Hospital of Medical School Nanjing University  Nanjing 210008 P. R. 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