Safer Than Safe: Lipid Nanoparticulate Encapsulation of Tacrolimus with Enhanced Targeting and Improved Safety for Atopic Dermatitis

摘要

Atopic dermatitis (AD) is a skin disorder having significant impact worldwide, characterized by itchy, erythematous and intensely pruritic rash with periods of remission. Tacrolimus is the drug-of-choice in treatment of many immune mediated dermatoses including AD. Despite being effective, most common adverse events of tacrolimus are burning sensation and pruritus at the application site prompting for development of novel carrier that could effectively target tacrolimus to site-of-action without producing undesirable toxic-effects. Tacrolimus loaded lipid nanoparticles (T-LN) were developed and evaluated comparatively for enhanced targeting potential to site of action and improved safety with commercially available ointment product, Protopic as reference. T-LN was successfully developed by high pressure homogenization technique. Significantly higher drug release and skin permeating properties were observed for T-LN as compared to reference. T-LN suppressed inflammatory response in vivo by 3.5 times more efficiently than reference, demonstrating its improved efficacy. Entrapment of tacrolimus in lipid nanoparticles avoided direct contact of drug with skin; alleviating drug related local side effects.