Topical drug delivery of licorice flavonoids and their structure-affinity relationship with the porcine skin

Abstract

Traditional Chinese medicine (TCM) possesses a long history of clinical application in the transdermal prescriptions, however, their transdermal mechanisms had not been clearly elucidated ascribing to their complex ingredients and different content. In this work, we firstly provide insights reports on the transdermal mechanisms of licorice flavonoids (LFs) extracts and the structure-affinity relationship between LFs compounds and the skin. The permeation properties of LFs extracts were conducted on the porcine skin and rat skin. It was highlighted that chalones and flavanone molecules were easier to permeate through the skin from LFs extracts than isoflavone. Differ from other LFs compounds, insoluble licochalcone A and licoflavone A obtained a higher permeation amount from LFs extracts than its corresponding monomer ingredients affirmed through molecular dynamics simulation study. In the stratum corneum (SC), among 33 kinds of flavonoids, glabridin possessed the highest compatibility with the skin lipids. Furthermore, interaction parameters (χ) values between the drugs and ceramide were negatively correlated with the number of hydrogen bond donor (HBD), polarizability and polar surface area of LFs compounds. The HBD of LFs molecules could help drugs bind to the skin lipids and then formed appropriate hydrogen bond interactions with the skin lipids, further improving the affinity between the drugs and the skin. Moreover, LFs components permeated through the porcine skin by disturbing the lipids arrangement in the SC. In the epidermis and dermis, the positive number and absorption rate of LFs extracts by HaCaT cells was significantly higher than melanocytes and HSF cells after 6 h. This study provided a new approach to unveil the molecular mechanisms of LFs permeation, which gave a reference for permeation of other TCM extracts.