Skin Barrier and Vaccination

The Skin Barrier and Vaccination group is led by Prof. Joke Bouwstra. One of the key functions of the skin is its barrier function, which is located in the uppermost layer of the skin, the stratum corneum. The stratum corneum consists of enucleated dead cells (corneocytes) embedded in a lipid matrix. The stratum corneum controls the flux of substances into and out of the body and protects the body from unwanted influences from the environment. This makes the delivery of high molecular weight compounds, such as therapeutic proteins and antigens a challenge. For this reason specialized drug delivery systems are developed. In our studies we use microneedles and we mainly focus on vaccination. As modern antigens often lack a strong antigenicity, the antigens are combined with adjuvants and/or encapsulated in nanoparticles to enhance the immune response.

The lipid matrix in the stratum corneum plays a crucial role in the skin barrier function. The lipids assemble in crystalline lipid lamellae. The crystalline nature and the presence of proper lamellar phases limit the diffusion of compounds travelling along this lipid matrix. Perturbations in the lipid composition and organisation will have a profound impact on the diffusion process as this will facilitate intercellular penetration and as such reduce the skin barrier. In this research we focus on changes in the barrier function of inflammatory skin diseases and how to repair this barrier by using formulations. Most of the studies have been performed in atopic dermatitis skin as this is the most prevalent inflammatory skin disease: in Western countries around 25% of the young children are suffering from this disease. In our research we use cultured human skin and lipid model systems to study in detail the barrier function and the changes in this barrier induced by inflammation.

Research projects

• Hollow, coated and dissolvable microneedles for intradermal vaccine administration
• Intradermal tuberculose vaccination by means of microneedles
• Design of formulations for skin barrier repair of atopic dermatitis patients
• Model lipid membranes to study skin barrier properties
• Development of human skin equivalents closely mimicking the in vivo human skin barrier