Effervescent Microneedles for the Codelivery of Chitosan Nanoparticles and Indocyanine Green To Enhance the Treatment of Diet-Induced Obesity in Mice

Obesity is a major global health challenge, significantly elevating the risk of cardiovascular disease and type II diabetes. In this study, we identified that self-assembled stearic-acid-modified chitosan oligosaccharide (COA) nanoparticles can efficiently degrade lipid droplets in adipocytes via autolysosomal pathways. By integrating COA nanoparticles with photothermal therapy (PTT), we developed a combination therapy delivered through an effervescent microneedle (MN) patch for treating diet-induced obesity in mice. The effervescent MN patch demonstrated superior skin penetration due to the efficient separation of the needle tips from the backing layer. Over a four-week treatment period, the COA nanoparticle and indocyanine green coloaded MN patches dramatically reduced body weight and white adipose tissue in obese mice without affecting their food intake. Histological analysis further revealed a reduced lipid droplet size and increased expression of UCP-1 within adipose tissues in vivo. Additionally, the combination therapy improved glucose metabolism and insulin sensitivity in obese mice. These findings suggest that COA nanoparticles delivered via an MN patch, when combined with localized PTT, effectively combat obesity and its associated metabolic complications in an obese mouse model. This approach presents a promising alternative to oral and injectable weight loss medications, offering improved efficacy with fewer side effects.