In this work we have characterized the architecture and physical properties of pig skin epidermis including its permeability to different liposome formulations. Autofluorescence images show that cells in the epidermis, from the basal layer to the stratum corneum, are organized in clusters that are in turn separated by particular structures we named "canyons". These canyons start in the surface as a wrinkle, eventually closing and going all the way inside the epidermis as a distinct structure that reaches the stratum basale. This structure, described previously in the epidermis of mouse skin as "intercluster pathway", was suggested to be filled with an unknown material and offer low resistance to vesicle penetration. Analysis of LAURDAN Generalized Polarization images of pig skin show that the canyons are filled with a non-polar poorly hydrated material, similar to that observed in pig skin stratum corneum. These results together with the data obtained from skin autofluorescence images suggest that these canyons are invaginations/extension of SC material. Fluorescently labeled lipids incorporated into very flexible liposomes are able to penetrate into the skin, eventually reaching the basal layer and the dermis plane. The presence of charged lipids in the liposomes enhances size stability and thus the efficiency of penetration.