Bicelle-induced skin penetration mechanism for hydrophilic molecules

In this study, we demonstrated that the disk-shaped structures, bicelles, composed of 1,2-dipalmitoyl-<i>glycero</i>-3-phosphocholine (DPPC) and 1,2-diheptanoyl-<i>sn</i>-glycero-3-phosphocholine (DHPC) enhance the transdermal delivery of hydrophilic and high-molecular-weight compounds by forming water-containing lamellar structures within the skin barrier, stratum corneum (SC). Skin permeation studies using fluorescent probes and cy3 modified RNA oligonucleotide revealed that bicelle pretreatment significantly enhanced their skin penetration. Furthermore, the interaction mechanism between bicelles and SC was elucidated using small-angle X-ray scattering (SAXS) and small-angle neutron scattering (SANS). The results showed that bicelles collapsed within the SC and reorganized into hydrated lamellae primarily composed of DPPC, which served as the new permeation pathway. Unlike DPPC vesicles, bicelles enhanced skin permeability without disrupting the original lamellar structures of intercellular lipids in the SC, thereby maintaining the skin barrier function. These findings reveal a novel mechanism of bicelle-mediated skin penetration and highlight their potential as safe and effective carriers for transdermal drug delivery.