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

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 alpha-lactalbumin (alpha-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.