Self-assembled hyaluronic acid nanoparticles delivered by polymeric microneedles for targeted and long-acting therapy of psoriasis

Psoriasis is an autoimmune-driven inflammatory skin disease, clinically characterized by skin thickening, erythema, and scaling, significantly impacting patients’ life quality and mental health. Clinically, oral pill or injection of methotrexate (MTX) formulation is a common route for psoriasis therapy, while both methods often cause undesired toxicity due to systemic administration, and limit patient compliance because of the frequent-dosing requirement. Here, we introduce a dissolvable microneedle (MN) patch made of polyvinyl alcohol (PVA) that incorporates self-assembled hyaluronic acid (HA) nanoparticles (NPs) conjugating MTX, which is designed for treating skin diseases, offering reduced adverse effects and improved patient adherence through its targeted and long-acting properties. Upon transdermal delivery via polymeric MNs, the HA-based therapeutic NPs actively target to the inflammatory skin cells via the interaction of HA group with CD44 protein that is highly expressed on the cell membrane in the psoriatic skin. Moreover, the HA-based NPs undergo slow dissociation, thereby achieving sustained release of the MTX drug at the lesion site over 7 days. Due to the favorite features, in the imiquimod (IMQ)-induced psoriatic mouse, only one application of the polymeric MN patch achieves diminished epidermal hyperplasia, and reduced inflammatory factors expression, ultimately improving the psoriasis-like skin condition in vivo.