Phycocyanin/Hyaluronic Acid Microneedle Patches Loaded with Celastrol Nanoparticles for Synergistic Treatment of Diabetic Nephropathy.

Although multifunctional drug delivery systems have shown significant potential in the treatment of diabetic nephropathy (DN), developing an efficient synergistic drug delivery strategy remains a major challenge. The purpose of this paper is to develop a nanoparticle-loaded microneedle (MN) patch transdermal drug delivery system aimed at achieving blood glucose control and reactive oxygen species (ROS) scavenging for the synergistic treatment of DN. MNs are composed of hyaluronic acid and phycocyanin (PC), both exhibiting excellent biocompatibility and degradation properties. Subsequently, insulin and celastrol (CEL)-based nanoparticles were incorporated into the MN to create the transdermal drug delivery platform (MN-IN&NPs). MN-IN&NPs can penetrate through the stratum corneum of skin and reach the dermis layer. Accompanied by the dissolution of MN, PC, insulin, and CEL-based NPs are continuously released. PC possesses anti-inflammatory and antioxidant properties that enable it to scavenge excessive ROS, thereby exerting synergistic effects alongside CEL nanoparticles. Furthermore, MN-IN&NPs significantly enhance drug transdermal delivery efficiency, while prolonging insulin's action duration. Therefore, MN-IN&NPs effectively integrate blood glucose control with ROS scavenging functions, presenting a promising therapeutic strategy for DN.