Anti-inflammatory unimolecular micelles of redox-responsive hyperbranched polycurcumin amphiphiles with enhanced anti-inflammatory efficacy in vitro and in vivo

Inflammation is a critical immune response to various stimuli but can lead to diseases when uncontrolled. Commonly used anti-inflammatory drugs usually associated with side effects, natural products such as curcumin (CUR) have emerged as a promising alternative but suffer from low bioavailability. This study introduces a novel nanocarrier, amphiphilic hyperbranched polyprodrug (P(ACPP-co-CURMA)-b-POEGMA, PACE), designed to enhance the anti-inflammatory activity of CUR. PACE micelles, formed from a hydrophobic hyperbranched polyprodrug core and hydrophilic POEGMA corona, demonstrated remarkable stability, even upon dilution, and efficiently released CUR in response to the reductive intracellular environment. These micelles were biocompatible and effectively internalized by macrophages. In both in vitro and in vivo studies, PACE micelles demonstrated significant anti-inflammatory activity, reducing ROS levels, down-regulating pro-inflammatory cytokines, and alleviating inflammation. This work highlights the potential of PACE micelles as a promising platform for targeted and responsive anti-inflammatory therapy, with implications for treating inflammatory disorders.