Penetration enhancer-containing vesicles: does the penetration enhancer structure affect topical drug delivery?

The aim of this study was to elucidate the influence of the edge activator structure on the properties of novel deformable liposomes, Penetration Enhancer-containing Vesicles (PEVs), capable of delivering drugs to the skin. The PEVs were prepared by testing five different amphiphilic penetra- tion enhancers as edge activators in the bilayer composition, together with soy phosphatidylcholine and oleic acid. The penetration enhancers contained the same lipophilic tail (one or more C -C carbon chains) and different hydrophilic heads. Conventional phospholipid liposomes were prepared and used as a control. Lidocaine was chosen as a model drug. Liquid and gelified PEVs were obtained, depending on the penetration enhancer used. The vesicular systems were charac- terized by measuring size distribution, zeta potential, incorporation efficiency, and monitoring these parameters over 90 days. Accelerated ageing tests were also performed to check the stability of the dispersions. The effects of the differen t 8 10 nature of the edge activator on the features of the obtained PEVs were assessed by TEM, SAXS and WAXS, rheologi- cal and deformab il ity studies . Higher in teractio n s of the mo st lip ophilic penetration enhancers with the lipid bilay- ers and a con sequen t h ig her stab ili ty and elasticity of the obtained PEVs were observed. In vitro experiments through pig skin confirmed the superior potential as carriers for lidocaine of the PEVs prepared with the most lipo- philic penetration enhancers, even in comparison with commercial EMLA cream