(685f) Mechanism of Transdermal Delivery of Macromolecules Assisted By Ionic Liquids
Using dextrans at varying molecular weights as the model molecule and choline-geranate (CAGE) as the model IL, we performed both experiments and theoretical modelling to investigate the transport mechanism. At the macroscopic scale, we measured skin permeabilities ex vivo, and for the first time, report remarkable enhancement for dextran up to 150kDa. At the microscopic scale, we probed CAGE-induced structural changes in both the lipid and protein components of the stratum corneum layer using spectroscopic methods. In addition to lipid extraction previously reported, we also observed changes in the protein secondary structure. Inspired by these new experimental findings, we theoretically model the transport of macromolecules via both intercellular and transcellular pathways and the predicted permeation enhancement agrees with experimental measurements. In the end, we discuss the scaling of molecular weight versus permeability, which shows a slower decay in the presence of CAGE. This striking change of scaling relationship sheds light on the advantage of IL over other enhancement techniques for large molecules in particular.
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