The presence of efflux transporters in the skin has already been described in several cell types in the epidermis, dermis and in dermal blood vessels. However, the exact role of these proteins has not been verified yet. The aim of this study is to characterise the function of the most abundant efflux pump (Permeabilit-glycoprotein, P-gp) in the drug absorption across the dermal barrier. In order to get insight in one aspect of transdermal drug absorption and drug­-drug interactions, two P-glycoprotein substrates (erythromycin and quinidine) were used as model substrates in cream and gel formulations. The penetration was tested through rat skin in the presence and absence of P-gp inhibitor with a widely used Franz-diffusion cell system and a skin-on-a-chip microfluidic device, which is a miniaturised, dynamic version of the Franz­-cell. The penetrated concentration of the drug was measured in the acceptor compartment using mass spectrometry technique. Our questions focused on 1) the effect of the P-gp inhibitor on substrate absorption; 2) the differences between the examined substrates (erythromycin versus quinidine); 3) the differences between the given formulations (cream versus gel); 4) the differences between the conventional Franz-diffusion cell system and the newly developed microfluidic device, and 5) the preservation of P-gp functionality after a freezing/melting procedure.

The results show that the absorbed drug concentration is significantly higher in the absence of the inhibitor, both in the case of erythromycin and quinidine (using either creams or gels), but only on freshly-prepared skin surfaces. That indicates that the P-glycoprotein plays an essential role in the transdermal penetration process as transporting the compound out from the cell, enabling its uptake by a deeper cell and pumping it into blood vessels. This phenomenon could not be observed on previously frozen skin samples, which means that the transporter protein is most probably deactivated, it cannot enhance the penetration.

The studies should be continued to have the precise characteristics of the penetration profile.
Besides the results demonstrating the transporter’s role in transdermal absorption, it can also be seen that the results gained from experiments on microfluidic device are reproducible and confirm the data of the classical method, therefore this technique might be an effective tool and good alternative to Franz-diffusion cell system.