Tetrandrine nanocrystals development for enhanced transdermal delivery and anti-psoriatic activity on imiquimod-induced psoriasis mouse model.

Psoriasis is an autoimmune inflammatory skin disease marked by erythema, swelling, keratinocyte hyperproliferation, and abnormal epidermal differentiation. Accumulating evidence highlights the critical role of regulatory T cells (Tregs) in suppressing pathological inflammation in psoriasis development. Tetrandrine (TET), a natural alkaloid, has shown anti-psoriasis potential by promoting immunosuppressive CD4+Foxp3+ Tregs via the mTNF-TNFR2 pathway. To overcome poor aqueous solubility/dissolution and limited skin penetration, this project has developed tetrandrine nanocrystals (TET-NCs) for topical delivery. The wet milling process was optimized in terms of milling parameters on particle size and polydispersity index (PDI). The obtained TET-NCs had uniform particle size and good storage stability. After loading them into hyaluronic acid gels (TET-NCs gel), the formulations were stable in rheological properties under refrigerated conditions. In vitro release experiments showed that the nanocrystals exhibited moderately enhanced release at slightly acidic pH. In vitro and ex vivo transdermal evaluations demonstrated enhanced skin penetration. The therapeutic efficacy of TET-NCs gel was evaluated on imiquimod-induced psoriasis-like model, and results demonstrated that psoriatic skin treated with TET-NCs gel exhibited improvements in both phenotypic and histopathological characteristics. Compared with the imiquimod group, levels of cytokines TNF-α, IL-6, IL-17A, and IL-23 were significantly reduced and the proportion of Tregs had increased. This study provides an effective nanocrystal strategy to overcome the transdermal delivery of tetrandrine for psoriasis treatment.