Dermal Application of Proteins : Development and Characterisation of an Application System
The development of a dermal formulation containing a protein drug offers novel therapeutic options, but also comprises new challenges regarding the formulation development. Aspects to consider are the high molecular weight of proteins, the polarity and their sensitivity to external conditions. Hydrolytic sensitivity can be one critical property of a protein that causes a decreased stability and hence has been examined in this study. Microemulsions (MEs) or more precisely pre-microemulsion concentrates were chosen as promising topical formulations for hydrolytic sensitive proteins. Due to their spontaneous formation after mixing the ingredients, MEs enable a separated storage of the aqueous and the lipophilic phase in a two-chamber-system. The protein is suspended in the lipophilic phase during storage and only dissolved in the aqueous part of the ME shortly before the application. For the ME formation Lipoid® S LPC 80 (Lip80) was chosen as suitable surfactant. Formulation stability, the ability to serve as protein vehicle system and the tolerability on human skin were analysed with a model enzyme (catalase) in comparison to a reference ME stabilised by PEGylated surfactants. Since proteins are high molecular weight drugs, a microneedle device supported the penetration to overcome the skin barrier. Dermastamp® was selected and examined in combination with Lip80-ME as well as with the reference ME. The immunological response was measured by the release of cytokines, the cell viability and morphological changes. The stability and activity of model protein in Lip80-ME were more favourable than the reference ME. The superiority of Lip80-ME was confirmed by a lower irritation potential on reconstructed human skin. Moreover, this formulation showed the property to reduce the local irritation caused by the needle device. To sum up, the developed combination of Dermastamp® and Lip80-ME is a promising approach in the dermal application of proteins.