Correlations Between Skin Barrier Integrity and Delivery of Hydrophilic Molecules in the Presence of Penetration Enhancers.

Abstract

We investigated the potential correlations between skin barrier integrity and hydrophilic drugs distribution in skin in the presence of different types of penetration enhancers (PEs) and their combinations. We measured skin conductivity to evaluate skin barrier integrity before and after the topical application of different chemical PEs, physical PE, peptide PE and their combinations in vitro. We also investigated their effect on the skin distribution profiles of two hydrophilic model drugs, Fluorescein sodium (376Da) and Fluorescein isothiocyanate-dextrans 10 (10 KDa). The physical PE significantly increased the skin conductivity compared to all other PEs, while the peptide PE had no effect on it. The drug deposition in different skin layers was not only dependent on PE applied but also its own molecular weight. We further found two excellent correlations: one (R2= 0.9388) between skin barrier integrity and total skin absorption of FNa and another one(R2= 0.9212) between skin barrier integrity and the deposition of FNa in dermis and receptor in presence of chemical or physical PEs and their combinations. The total skin absorption or the deposition in dermis and receptor of small hydrophilic drug in the presence of chemical and physical PEs and their combinations show a good correlation with skin barrier integrity. However, such correlations hold true neither for large hydrophilic drug nor for peptide PE. All good relationships found in this work will allow screening suitable PEs or combinations by measuring the skin conductivity induced by corresponding PEs. Graphical Abstract The total skin absorption of small hydrophilic drug shows a good correlation with skin barrier integrity in the presence of chemical and physical penetration enhancers and their combinations. However, such a correlation hold true neither for large hydrophilic drug nor for peptide penetration enhancer.