Umbilical therapy for promoting transdermal delivery of topical formulations: Enhanced effect and underlying mechanism

Umbilical paste therapy is a promising method to promote transdermal drug delivery of topical formulations. This work investigated the effect and mechanism of transdermal drug delivery through the umbilical skin. The transdermal permeation studies showed the phenomenon of higher cumulative penetration and faster penetration rates for drug through the umbilical skin compared with non-umbilical skin, namely umbilical pro-permeability. This special transdermal permeability of drugs is influenced by their molecular weight, logP value, ability to form hydrogen bonds, and molecular volume. The underlying mechanism of umbilical pro-permeability was elucidated from unique structure and regulation the effect of drugs on microcirculation in the umbilical skin. Mechanistic studies revealed that this phenomenon was not only associated with the structural and physiological properties of the skin but also to the interactions between drugs and different skin layers. The umbilical pro-permeation is attributed to the thinner stratum corneum layer, differences in stratum corneum lipid composition and keratin structure, and lower levels of intercellular tight junction proteins in the viable epidermis and dermis layer of the skin. Our research indicated that umbilical paste therapy enhanced the transdermal delivery and absorption of drugs by stimulating local blood flow through mast cell activation. Surprisingly, skin temperature modulation and calcitonin gene-related peptide and substance P levels did not appear to significantly affect this process. In conclusion, umbilical drug administration, as a straightforward and non-invasive approach to enhance transdermal drug delivery, presents novel concepts for continued investigation and practical implementation of transdermal drug delivery systems.