Reversible skin permeabilization for transdermal delivery of macromolecules

Great advances in transdermal delivery of macromolecules have been made within the last few years using ultradeformable liposomes, electroporation, and low-frequency ultrasound, each of which has been shown to deliver macromolecules at clinically useful rates. Until recently, delivery of high-molecular-weight compounds across the skin was not a realistic option, since the skin's great barrier properties prevent transport of macromolecules across human skin at therapeutically relevant rates. An overview of chemical (liposomes and chemical enhancers) and physical (iontophoresis, electroporation, and ultrasound) methods of enhancement is presented, with emphasis on work published within the last two years. Key experimental results and their mechanistic interpretation are provided for each enhancement technique.