Microneedle Patch Delivery of Capsaicin‐Containing α‐Lactalbumin Nanomicelles to Adipocytes Achieves Potent Anti‐Obesity Effects

Abstract The development of a minimally invasive therapy for local targeting of adipose tissues could represent an attractive approach for treating obesity. Here, the development and successful application of a nanomedicine that uses α‐lactalbumin (α‐lac) nanomicelles (M) to encapsulate the known anti‐obesity agent capsaicin (Cap), which is delivered directly to adipose tissue via a microneedle patch (MP), is reported. Testing with a 3T3‐L1 adipocyte model shows that M (Cap) reduces lipid droplet content by regulating adipogenesis and improving mitochondrial biogenesis. The MP enables efficient M (Cap) penetration into abdominal subcutaneous adipose tissue, and M (Cap) can be endocytosed by white adipocytes. Experiments using a high fat diet‐induced obese mice model shows that MP‐delivered M (Cap) confers dramatic weight loss and adipose tissue browning, and follow‐up mechanistic investigations indicate (among other impacts) activated energy metabolism, increased mitochondrial biogenesis, and the induction of well‐known adipocyte browning markers. The study supports that MP‐M (Cap) treatment, which could be developed as a self‐administered therapy based on skin attachment for around 30 min, has a promising future as a non‐invasive approach for treating obesity.