Stratum corneum targeting by dendritic core-multishell-nanocarriers in a mouse model of psoriasis

Inflammatory disorders of the skin pose particular therapeutic challenges due to complex structural and functional alterations of the skin barrier. Penetration of several anti-inflammatory drugs is particularly problematic in psoriasis, a common dermatitis condition with epidermal hyperplasia and hyperkeratosis. Here, we tested in vivo dermal penetration and biological effects of dendritic core-multishell-nanocarriers (CMS) in a murine skin model of psoriasis and compared it to healthy skin. In both groups, CMS exclusively localized to the stratum corneum of the epidermis with only very sporadic uptake by Langerhans cells. Furthermore, penetration into the viable epidermis of nile red as a model for lipophilic compounds was enhanced by CMS. CMS proved fully biocompatible in several in vitro assays and on normal and psoriatic mouse skin. The observations support the concept of CMS as promising candidates for drug delivery in inflammatory hyperkeratotic skin disorders in vivo.

Graphical AbstractThere is a strong medical need for more effective dermal drug delivery systems for poorly penetrating drugs in inflammatory skin diseases such as psoriasis. We studied the penetration and effects of core-multishell-nanocarriers (CMS), a novel concept for transporting poorly penetrating drugs into the skin. Following topical application, CMS accumulated in the stratum corneum without deeper penetration and with no differences between healthy and psoriasis-like mouse skin. Furthermore, penetration of nile red as a model cargo into the viable epidermis was enabled when CMS were used as carrier and compared to a standard cream formulation.287