Dendritic hPG-amid-C18-mPEG core-multishell nanocarriers (CMS) represent a
novel class of unimolecular micelles that hold great potential as drug
transporters, e.g., to facilitate topical therapy in skin diseases. Atopic
dermatitis is among the most common inflammatory skin disorders with complex
barrier alterations which may affect the efficacy of topical treatment. Here,
we tested the penetration behavior and identified target structures of
unloaded CMS after topical administration in healthy mice and in mice with
oxazolone-induced atopic dermatitis. We further examined whole body
distribution and possible systemic side effects after simulating high dosage
dermal penetration by subcutaneous injection. Following topical
administration, CMS accumulated in the stratum corneum without penetration
into deeper viable epidermal layers. The same was observed in atopic
dermatitis mice, indicating that barrier alterations in atopic dermatitis had
no influence on the penetration of CMS. Following subcutaneous injection, CMS
were deposited in the regional lymph nodes as well as in liver, spleen, lung,
and kidney. However, in vitro toxicity tests, clinical data, and morphometry-
assisted histopathological analyses yielded no evidence of any toxic or
otherwise adverse local or systemic effects of CMS, nor did they affect the
severity or course of atopic dermatitis. Taken together, CMS accumulate in the
stratum corneum in both healthy and inflammatory skin and appear to be highly
biocompatible in the mouse even under conditions of atopic dermatitis and thus
could potentially serve to create a depot for anti-inflammatory drugs in the
skin