A Programmed Drug‐Loaded and Penetration‐Delivery Functionalized Microneedle Patch for Synergistic Obesity Treatment

The inherent pathological microenvironment of adipose tissue restricts accumulation and deep penetration delivery of drugs, resulting in the lack of an ideal strategy for obesity management. In view of this, a dual-layered microneedle system was developed for obesity treatment. Firstly, capsaicin (Cap) and mitochondrial uncoupler BAM15 were respectively co-assembled with solutol HS-15 (HS) to obtain functionalized nanodrugs (HS@Cap NPs or HS@BAM15 NPs). Then they were integrated into the microneedle system (BC-MNs). The BC-MNs realize programmed controlled release of nanodrugs in subcutaneous tissue via transdermal delivery. HS@Cap NPs rapidly release at the needle tip to penetrate deep white adipose tissue and promote its browning. Sequentially, slowly released HS@BAM15 NPs then accumulate in beige adipocytes to enhance cell metabolism, achieving synergistic anti-obesity effects. Finally, both in vitro and in vivo experiments analyzed and validated the therapeutic efficacy of this system for obesity. In summary, the above-mentioned cascade co-treatment strategy based on the microneedle drug delivery system provides a potential possibility for clinical management and treatment of obesity.