Nanoparticles for transcutaneous vaccination Steffi Hansen1,2 * and Claus-Michael Lehr1,2 1Department of Drug Delivery, Helmholtz-Institute for

The living epidermis and dermis are rich in antigen presenting cells (APCs). Their activation can elicit a strong humoral and cellular immune response as well as mucosal immunity. Therefore, the skin is a very attractive site for vaccination, and an intrader-mal application of antigen may be much more effec-tive than a subcutaneous or intramuscular injection. However, the stratum corneum (SC) is a most effec-tive barrier against the invasion of topically applied vaccines. Products which have reached the stage of clinical testing, avoid this problem by injecting the nano-vaccine intradermally or by employing a barrier disrupting method and applying the vaccine to a relatively large skin area. Needle-free vaccina-tion is desirable from a number of aspects: ease of application, improved patient acceptance and less risk of infection among them. Nanocarriers can be designed in a way that they can overcome the SC. Also incorporation into nanocarriers protects instable antigen from degradation, improves uptake and processing by APCs, and facilitates endosomal escape and nuclear delivery of DNA vaccines. In addition, sustained release systems may build a depot in the tissue gradually releasing antigen which may avoid booster doses. Therefore, nanofor-mulations of vaccines for transcutaneous immuniza-tion are currently a very dynamic field of research. Among the huge variety of nanocarrier systems that are investigated hopes lie on ultra-flexible lipo-somes, superfine rigid nanoparticles and nanocarri-ers, which are taken up by hair follicles. The potential and pitfalls associated with these three classes of carriers will be discussed