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Psoriasis skin lesions have a vicious cycle where hypoxia and reactive oxygen species (ROS) amplify each other and reduce keratinocyte sensitivity to methotrexate. We designed a double-layer microneedle patch: the base of the needles is made of soluble polyvinylpyrrolidone loaded with methotrexate, which quickly releases the drug after insertion to provide early epidermal intervention; the needle tips contain manganese dioxide nanoenzymes wrapped in phenylboronic acid-crosslinked hydrogel, which respond to high ROS levels in the dermis, remove ROS, and generate oxygen, breaking the hypoxia-oxidative stress cycle and restoring keratinocyte response to the drug. In imiquimod-induced psoriasis-like mice, this patch enhanced the therapeutic effect of methotrexate.
