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.