Dermapen-mediated microchannels enable deep cutaneous delivery of liposomal and particulate model systems, with...

Delivering hydrophilic macromolecules and particulate systems into skin is limited by the strong transport resistance of the stratum corneum and viable epidermis. Microneedling offers a potential solution, but its usefulness depends on whether a practical treatment protocol can reproducibly generate barrier-bypassing microchannels. Here, we investigated whether an electrically powered microneedling pen, Dermapen, can be used to create such access pathways in excised human skin and whether this improves delivery of liposomal, macromolecular, and particulate model systems. A 12-needle Dermapen protocol generated quantifiable microchannels with a mean measured depth of 450 ± 156 µm, extending well beyond the principal epidermal barrier layers. In Franz diffusion cells, Dermapen pretreatment markedly increased 30 h cumulative recovered fluorescence from Texas Red-dextran-containing liposome dispersions and increased fluorescence signal within the viable epidermis and dermis by cryosection imaging and depth profiling. In intact skin, formulation-dependent differences were more evident, whereas these differences were greatly reduced once microchannels were created, consistent with physical barrier bypass as the dominant mechanism. Microneedling also enhanced intraskin delivery across distinct payload classes, including free 70 kDa dextran, liposome dispersions, and 1 µm fluorescent particles, and brief post-application topical massage further amplified delivery. These findings show that controlled Dermapen-generated microchannels are the primary enabler of deep intraskin drug delivery, while post-application massage can further increase payload deposition. By linking quantified microchannel formation to downstream transport of multiple payload classes, the study provides a practical framework for reproducible device-assisted cutaneous and transdermal delivery research.