Elongated silica microparticles for enhanced delivery of tailorable nanoemulsion as a potential platform for transdermal drug delivery

The purpose of this research was to evaluate the combination of elongated silica microparticles (EMP) and tailorable nanoemulsions (TNE) to control topical delivery of hydrophobic drug surrogates. The microparticles penetrate through the epidermis and stop at the dermal-epidermal junction (DEJ). TNE is unusually stable because the oil core allows high loading levels and the surface properties can be easily controlled. In this study we incorporated a fluorescent lipophilic dye, DiI, as a hydrophobic drug surrogate into TNE for visualization with microscopy. In addition, the core droplet of TNE was packed with pharmaceutical grade lipid (glycerol) instead of DiI and imaged by coherent anti-Stoke Raman scattering (CARS) microscopy to characterize the delivery of lipid in freshly excised human skin. We compared four different coating approaches to combine EMP and TNE. These data showed that a freeze-dried formulation with alginate cross-linking showed 100% of the detectable TNE were retained on the EMP. When this dry form of EMP-TNE was applied to excised, living human abdominal skin, the EMP penetrated to the DEJ and we observed that the controlled release of TNE thereafter. This formulation resulted in a sustained release profile, whereas a freeze dried formulation without crosslinking showed an immediate burst type of release profile. DiI could be detected as deep as 60 micron into the skin showing a potential usage of TNE as a hydrophobic drug carrier in combination with a physical penetration enhancing technology. These data show that a dry, slow release formulation containing EMP coated with TNE can effectively deliver a hydrophobic payload deep into the human epidermis and controllably release that payload.