Sodium diclofenac and cell-penetrating peptides embedded in H_II mesophases: Physical characterization and delivery

Glycerol monooleate (GMO)-based mesophases offer extensive prospects for incorporation of various bioactive molecules. This work deals with the solubilization of selected cell-penetrating peptides (CPPs) together with sodium diclofenac (Na-DFC) within the H_II mesophase for transdermal applications. The effect of CPPs such as RALA (an amphipatic CPP), penetratin (PEN), and oligoarginine (NONA) on Na-DFC skin permeation kinetics to provide controlled release and tune the drug transdermal diffusion was studied. The location of the drug and the CPPs within the mesophase was probed by DSC and FTIR. Na-DFC was found to be located at the interfacial region between the surfactant chains, leading to denser H_II mesophase. The hydrophilic NONA was intercalated into the aqueous cylinders and caused their swelling. It induced a significant decrease in the hydrogen binding between the GMO carbonyls and their surrounding. The amphiphilic PEN was entrapped within two different regions, depending on its concentration. PEN and NONA improved Na-DFC permeation by 100%, whereas RALA enhanced permeation by 50%. When estimating Na-DFC migration rate out of the mesophase toward surrounding aqueous media, it appeared to be slower with the CPPs. The peptides were not involved at this diffusion-controlled step. It seems that their effect on skin permeation is based on their specific interaction with the skin.