Co-assembled ion-pair complex nanoparticles from tranexamic acid and metformin with enhanced transdermal efficacy...

The aesthetic effect of skin pigmentation caused by ultraviolet radiation and its increased risk of melanoma have received much attention. Non-invasive transdermal delivery has been widely recognized, but the transdermal limitation of hydrophilic active ingredients through the skin barrier and the multi-target action pathways of inhibition of melanin synthesis still need to be further explored. We have developed a self-assembled nanosystem (S-PMT), which was co-assembled from an ion pair complex formed by tranexamic acid (TXA) and metformin (Met) with palmitoyl epigallocatechin gallate (pEGCG). Transdermal delivery evaluation showed that S-PMT significantly enhanced the skin flux and intradermal retention of the active ingredient through its ion-pair properties, self-assembled nanostructure, and penetration enhancer salcaprozate sodium (SNAC), outperforming TXA or the TXA/Met physical mixture. In vitro and in vivo studies have confirmed that S-PMT could synergistically inhibit p38/PKA-MITF pathways through scavenging reactive oxygen species (ROS) and tyrosinase signaling pathways, significantly suppressing UVB-induced intracellular tyrosinase activity and melanin synthesis and inflammatory cytokine expression. Simultaneously, it exhibited excellent safety and skin tolerance. These results provided a basis for the clinical application of S-PMT in UVB induced skin pigmentation, making it a promising non-invasive therapeutic platform for skin pigmentation treatment.