Methotrexate (MTX) is one of the first-line drugs used for the treatment of moderate to severe
psoriasis. However, low bioavailability and systemic side effects of traditional oral and
injectable MTX greatly limit its clinical application. Delivering MTX using dissolving microneedles (MNs) into
psoriasis-like skin lesion could improve the in situ
therapeutic effects with higher bioavailability and less side effects. Here, we propose a novel therapeutic approach for
psoriasis involving MN-assisted percutaneous delivery of
chitosan-coated hollow mesoporous
silica nanoparticles containing MTX (MTX@
HMSN/CS). The MTX@
HMSN/CS-loaded MNs were strong enough to successfully penetrate the psoriasiform thickened epidermis, allowing MTX@
HMSN/CS to be accurately delivered to the site of skin lesion following the rapid dissolution of MNs. MTX was then released continuously from
HMSN/CS for at least one week to maintain effective therapeutic drug concentration for skin lesion with long-term anti-proliferative and anti-inflammatory effects. Incubation with MTX@
HMSN/CS not only inhibited the proliferation of human immortalized keratinocytes (HaCaT cells), but also significantly reduced the expression of proinflammatory
cytokines and
chemokines. In addition, MTX@
HMSN/CS-loaded MNs showed better efficacy in alleviating
psoriasis-like skin
inflammation than MTX-loaded MNs at the same dose. Compared to psoriasiform mice treated with 15.8 μg MTX-loaded MNs every day, 47.4 μg MTX@
HMSN/CS-loaded MNs reduce the frequency of treatment to once every 3 days and achieve comparable amelioration. Therefore, MTX@
HMSN/CS loaded MNs are a promising treatment strategy for
psoriasis due to their durability, efficacy, convenience, and safety in relieving
psoriasis-like skin
inflammation.