Pharmaceutical Design and Clinical Translation Challenges of Baicalein Anti-Tumor Nano-Preparations in Traditional Chinese Medicine

As the main active ingredient of Radix Scutellariae, Baicalein has multi-target anti-tumor effects. However, its clinical application is limited by low water solubility and bioavailability. This study systematically elaborates on the pharmaceutical design principles and clinical translation challenges of baicalein nano-preparations. Solubilization technologies such as nanocrystals and polymer micelles can increase the solubility of baicalein by 120 times; targeted delivery systems (e.g., folic acid/RGD modification) can increase the accumulation of the drug in tumors by 3.8 times; and pH/enzyme-responsive controlled-release systems can achieve tumor-specific drug delivery. However, the process stability of large-scale production (batch-to-batch variation <15%), the lack of long-term toxicity data (only two six-month studies), and the regulatory differences between the East and the West (NMPA requires 15 characteristic peaks vs. FDA requires five indicators) remain the main obstacles to translation. In the future, new technologies such as artificial intelligence prediction and organ-on-a-chip evaluation should be combined to promote their clinical application in integrating traditional Chinese and Western medicine. This article introduces the anti-tumor drug baicalein and its clinical translation bottlenecks. It provides systematic research ideas, methodological references, pharmaceutical design principles, and clinical translation considerations for developing nano-preparations of active ingredients in traditional Chinese medicine.