A Novel Microfluidic Strategy for the Fabrication of α‐Lactalbumin Nanomicelles Paves a New Path for Antiobesity Technology

Obesity, a global chronic metabolic disorder, poses a major risk for multiple comorbidities. Sulforaphene (SE) exerts antiobesity effects but suffers from poor water solubility, low bioavailability, and flawed traditional nanocarrier fabrication. Herein, we report an optimized 3D obstacle Tesla valve micromixer (3D-OTVM) platform. This system enables uniform mixing and controlled shear force, overcoming traditional fabrication bottlenecks. Using this platform, we constructed M(α-Lac-SE) nanomicelles via controlled hydrolysis of α-lactalbumin, and demonstrated that M(α-Lac-SE) exerts synergistic lipid-lowering effects by activating white adipose beiging alongside inhibiting adipogenesis. Notably, an 8-week head-to-head comparison in high-fat diet (HFD)-induced obese mice showed that M(α-Lac-SE) produced stronger fat-reducing effects than semaglutide under the present experimental conditions, while inducing markedly lower kaolin intake-associated pica behavior, a surrogate indicator of nausea-like gastrointestinal discomfort. In vitro, M(α-Lac-SE) entered adipocytes via caveolin/lipid raft-mediated endocytosis with lysosomal escape, reducing lipid droplets by over 52%. In HFD-induced obese mice, M(α-Lac-SE) decreased body weight by 11.9% after 8 weeks of treatment, improved dyslipidemia and hepatic lipid accumulation, and showed no obvious abnormalities in serum biochemical indicators or major-organ histopathology. This work breaks delivery bottlenecks and provides a precise nanodelivery-based strategy for obesity intervention.