Mussel-Inspired Polydopamine Coating Enhances the Intracutaneous Drug Delivery from Nanostructured Lipid Carriers Dependently on a Follicular Pathway

Inspired by the structure and function of the mussel adhesive protein, a facile strategy involving oxidative polymerization of dopamine was proposed for surface modification of nanostructured lipid carriers (NLCs) to promote drug delivery in the skin. The formation of a polydopamine (PDA) layer rounding the surface of NLCs was confirmed by the X-ray photoelectron spectroscopy and the Fourier transform infrared spectroscopy studies. Using terbinafine (TBF) as a model drug, the in vitro permeation study revealed that the PDA coating significantly enhanced the delivery of TBF from NLCs to the deep skin layers, where the follicular pathway played an essential role as suggested by the hair follicle blocking and differential tape stripping experiments, as well as the laser scanning confocal microscopy study by using Nile red as the fluorescent probe. The cellular investigation indicated that the PDA coating led to a higher cellular uptake of nanoparticles in human immortalized keratinocytes (HaCaT) without causing additional cytotoxicity. Using endocytic inhibitors, it was found that the lipid raft/caveolae-mediated endocytosis was strongly involved in the internalization of both the PDA modified and unmodified NLCs. Our results suggested that surface modification of NLCs with PDA coating improved the intracutaneous drug delivery mainly via the follicular pathway, which provided an avenue for the development of potential drug delivery carriers for dermal use.