Study on the drug permeation mechanism from flurbiprofen-loaded glyceryl monooleyl ether-based lyotropic liquid crystalline nanoparticles across the skin: Synchrotron X-ray diffraction and confocal laser scanning microscopy study

Abstract

The mechanism underlying the skin permeation of flurbiprofen (FLU)-loaded, glyceryl monooleyl ether-based liquid crystalline nanoparticles (LCNs) with a hexagonal structure was examined by synchrotron X-ray diffraction and confocal laser scanning microscopy (CLSM). Fluorescent-labeled, FLU-loaded LCNs were prepared using coumarin 6 and rhodamine B 1,2-dihexadecanoyl-sn-glycero-3-phosphoethanolamine, triethylammonium salt (Rh-PE), which produce green and red fluorescence, respectively. Application of FLU-loaded LCNs to the hairless mouse stratum corneum (SC) induced expansion of the lattice spacing of the hexagonal structure with FLU release, as confirmed by the changes in the small-angle X-ray diffraction profiles. In addition, the FLU-loaded LCNs completely released FLU near the surface of the SC, which then penetrated the SC. Consequently, the repeat distance of the long periodicity phase was slightly modified. CLSM revealed green fluorescence in the epidermis and hair follicles and red fluorescence in the SC. In conclusion, LCNs adopt several permeation pathways: one is partly via the intercellular matrix and the other is the epidermis via hair follicles.