Microneedle system carrying Momordin Ic-loaded ROS-responsive hydrogel ameliorates psoriasis via targeted anti-inflammatory and reactive oxygen species (ROS)-scavenging mechanisms

Psoriasis is a chronic inflammatory skin condition with high oxidative stress and immune dysregulation. Current therapies are limited by side effects and inefficacy over long-term use, highlighting the need for targeted treatments. This study investigates a reactive oxygen species (ROS)-responsive hydrogel (HP)-dissolving microneedle system, loaded with Momordin Ic, designed for controlled, site-specific release to alleviate psoriasis. We hypothesized that this system could target psoriatic inflammation by reducing pro-inflammatory cytokines and oxidative stress. The Franz diffusion cell assay confirmed that Momordin Ic release was accelerated under elevated ROS conditions, demonstrating the stimuli-responsive nature of the hydrogel microneedles system. An imiquimod (IMQ)-induced psoriasis-like mouse model was used to evaluate the therapeutic efficacy of the Momordin Ic/HP microneedle system. The HP microneedles exhibited controlled Momordin Ic release under elevated ROS, and in vitro studies showed reduced ROS levels and blocked hyperproliferation in HaCaT keratinocytes. In vivo, the microneedle treatment alleviated psoriasis symptoms, reducing erythema, scaling, and epidermal thickness while downregulating inflammatory markers (IL-17A, TNF-α). These findings suggest that Momordin Ic/HP microneedles provide a promising therapeutic approach to treating inflammatory skin diseases like psoriasis by combining anti-inflammatory and ROS-scavenging functions.