Crisaborole-Loaded Nanoemulsion for Atopic Dermatitis: Localized Dermal Delivery of a Phosphodiesterase-4 Inhibitor

Background/Objectives: Crisaborole (CRB) is a phosphodiesterase-4 inhibitor used for the topical treatment of mild-to-moderate atopic dermatitis (AD). However, its low aqueous solubility presents challenges for topical formulation and localized drug delivery. This study aimed to develop a CRB-loaded nanoemulsion (CRB-NE) and evaluate its physicochemical and biopharmaceutical characteristics, tolerability, and anti-inflammatory activity.

Methods

CRB-NE (0.5% w/w) was developed using pseudo-ternary phase diagrams. Droplet size, morphology, rheological behavior, spreadability, and stability were characterized. Drug release and ex vivo permeation in human skin were evaluated. Biological compatibility was investigated using HaCaT keratinocytes and the hen's egg test-chorioallantoic membrane (HET-CAM) assay, while skin barrier compatibility was assessed in healthy volunteers. Anti-inflammatory activity was evaluated through IL-8 secretion in stimulated HaCaT cells and a xylene-induced ear inflammation model in mice.