Dissolving microneedle synergistic rocaglamide-loaded liposome to regulate abnormal neutrophils for anti-psoriasis

Psoriasis seriously affects the physical and mental health of patients. Rocaglamide (RocA), derived from Aglaia odorata, exhibits potent pharmacological activities. Although its efficacy in psoriasis is unclear, RocA could be a promising therapeutic drug. In this work, RocA showed a good therapeutic effect in psoriasis mice induced by imiquimod, and subsequent TMT-based proteomics analysis verified that the effect of RocA was related to IL-1 family cytokines. Furthermore, a RocA-loaded liposome (RocA@Lipo) was developed and encapsulated in the tip-layer of microneedles (MNs) to construct a MN-based nano drug delivery system (RocA@Lipo-MNs). In vitro HaCaT cell assays demonstrated that RocA@Lipo enhanced the cytotoxicity and cell uptake of RocA. In vivo, RocA@Lipo-MNs outperformed other RocA formulations in inhibiting psoriasis epidermal thickening and spleen enlargement. Immunohistochemical, ELISA, western blot, and PCR experiments further proved that RocA@Lipo-MNs could inhibit neutrophil infiltration in the skin, revealing that the anti-psoriasis mechanism of RocA was deemed to inhibit the binding of IL-1α and IL-1R1 to regulate the activation of MAPK and NF-κB pathways. Thus, the production of inflammatory factors and neutrophil chemokines was reduced, which was associated with apoptosis inhibition. Importantly, RocA@Lipo-MNs significantly improved the transdermal properties of RocA and exhibited good skin and blood safety. This work provides new ideas for the clinical application of RocA and the treatment options for psoriasis.