Tacrolimus ointment is a very effective therapy for atopic dermatitis (AD) but has a low and variable bioavailability and can produce pruritus and burning at the application site. An attempt was made to develop a novel carrier to aid deeper absorption without producing local adverse effects. Tacrolimus-loaded lipid nanoparticles (T-LN) were prepared and optimized for local application. In vitro studies showed that these provided much higher drug release, skin penetration and accumulation relative to the tacrolimus ointment. Skin irritation studies in rabbits revealed no erythema or edema on intact or abraded skin in contrast to the reference marketed product. These data augur well for a new delivery option for topical tacrolimus (Pople, ...