Microneedle-mediated transdermal H₂S gas therapy for psoriasis

Psoriasis is a common chronic skin disease. Current psoriasis treatments face challenges such as low drug bioavailability and side effects. Hydrogen sulfide (H₂S) can be a potential therapeutic for psoriasis, while developing an effective delivery system and a controlled release strategy is essential to guarantee its efficacy and safety. We report a responsive microneedle (MN)-mediated transdermal H₂S gas therapy for treating psoriasis. The phenylboronic acid-modified hyaluronic acid (HP) and a peptide H₂S donor (AlaCOS) are synthesized, which assemble into H₂S donating nanoparticles (HP-AC NPs). The HP-AC NPs efficiently release AlaCOS in aqueous solution or acidic conditions, which can further release H₂S triggered by aminopeptidase N (APN) and carbonic anhydrase (CA). Moreover, the HP-AC NPs can effectively downregulate the pro-inflammatory cytokines in macrophages. Furthermore, the HP-AC NP-loaded MNs (HP-AC MN) are prepared with sufficient mechanical strength to penetrate the stratum corneum barrier. In the psoriatic mouse model, the mice receiving the HP-AC MN treatment exhibit decreased epidermal thickness, reduced levels of pro-inflammatory cytokines, and induced M2 polarization of macrophages. This MN-mediated H₂S gas therapy represents a promising alternative for treating psoriasis.