Overcoming semipermeable barriers, such as the skin, with ultradeformable mixed lipid vesicles, transfersomes, liposomes, or mixed lipid micelles

We studied lipid aggregate penetration through nanoporous, semipermeable barriers by direct transport measurements in vitro and with the confocal laser scanning microscopy of the skin in vivo. We found that it is necessary to use mixed lipid bilayers with a low resistance to permeabilization and high flexibility to overcome narrow, normally confining pores. Partial molecular demixing in the stressed vesicle bilayer serves both purposes. An aggregate comprising a suitable blend of amphipats (Transfersome, Tfs) is, therefore, extremely deformable and easily crosses even very narrow pores (rTfs ≥ 10rpore, and possibly more). Each such vesicle then behaves as a responsive, self-optimizing, nanorobotic transport device. The mixed micelles with identical components or the simple vesicles (liposomes) with a similar size as that of unusually deformable vesicles do not share this quality. Liposomes only traverse barriers when rlipos ≤ 1.5rpore; they clog narrower pores, unless they get fragmented in/before the ori...