Separable cryo-microneedle patches delivery with capsaicin integrated mesoporous dopamine for obesity treatment.

Microneedle patch encapsulated with active medication holds significant potential promise in the realm of anti-obesity therapy. Nevertheless, the improvement of actives delivery efficiency remains a significant challenge. In this paper, we present novel separable cryo-microneedles patches delivered with capsaicin integrated mesoporous dopamine (mPDA) for obesity treatment through activating TRPV1 and inducing lipid droplet dissolution. Such patch is fabricated by cryogenic molding of biocompatible hydrogel tips, which can be easily inserted and left from skin through the thermoresponsive backing layer. Upon penetration, these tips could release mPDA-carrying capsaicin into the targeted subcutaneous adipose layer. In addition, when exposed to near infrared (NIR) light, these mPDA could rapidly convert the light energy into heat to increase the local temperature, thus accelerating the release of capsaicin from mPDA and the metabolic benefits of regional hyperthermia therapy. Based on these features, we have demonstrated that the multifunctional separated cryo-microneedles could significantly reduce weight and relieve obesity-associated pathological conditions with no adverse effect through an 8-week observation on high-fat diet (HFD) mice. Thus, we believe that our separable cryo-microneedles patches delivered with capsaicin integrated mPDA will open a new prospect for obesity treatment.