Dendritic nanoparticles for cutaneous drug delivery--testing in human skin and reconstructed human skin

Dendritic nanoparticles have been developed with auspicious properties like high loading capacity for guest molecules, low polydispersity and tunable end groups. Demonstrating increased cellular uptake and bypassed efflux transporters, dendritic nanoparticles may offer new treatment options for therapy-resistant diseases. New core-shell architectures address the drawbacks of initial approaches. Especially tecto-dendrimers, bearing low-radii dendrimers on the surface of a bigger dendrimer, as well as the core-multishell architectures with an alkyl inner shell and a monomethylpoly(ethylene glycol) outer shell, gained interest for dermatotherapy. Moreover, the integration of e.g. pH labile groups into dendritic nanoparticles may offer triggered drug release. However, before declaring dendritic nanoparticles as an ultimate drug delivery system for skin penetration, dendritic nanoparticles need to prove their efficacy and safety in non-clinical, and subsequently in clinical studies. Here, we review major characteristics of human skin, and thus target structures for topical drug delivery systems. Focusing on the use as in vitro test system, we summarize the features of reconstructed human skin. Since drug delivery systems are intended to be applied to diseased skin, we additionally review latest insights into disease-related changes in the highly prevalent skin diseases such as atopic dermatitis, and cutaneous squamous cell carcinoma, as well as in their respective human cell-based skin disease models. We will conclude with the proposal of an integrated test strategy to promote the introduction of dendritic nanoparticles into medicinal products.