ABSTRACT

This mini-review deals with microneedles and nanopatches, two innovative approaches to improve transdermal vaccination. Microneedles and nanopatches are expected to improve vaccination success, compliance, and cost reduction. A challenge to broadly establish this new strategy is the stabilization of the vaccines on the devices during sterilization and storage. 9.1 Vaccination via the Dermal RouteThe skin contains a large number of Langerhans cells, which are important professional antigen-presenting cells. In addition to these cells, dendritic cells in the skin are essential for the formation of sufficient defense activity against infectious intruders. Dendritic

cells recognize foreign antigens and elicit highly efficient immune responses to counterattack transdermal infections. Therefore, intradermal vaccination and thus the pathogen-specific stimulation of dendritic cells are plausible approaches. The most prominent limitations of standard vaccination devices such as needle and syringe or patches for transdermal diffusion are summarized in the following paragraphs. 9.2 Limitations of Standard Vaccination

ProceduresIntradermal immunization with vaccines in solution requires needle injection by medical personnel. It is often painful, time consuming and unreliable, as well as associated with needle injury and pathogen transmission (Kim et al., 2010). Accordingly, the compliance of the patients to be vaccinated is generally low. Moreover, the vaccination costs are very high due to the required high density of vaccine within the ampulla. A significant problem in the field of vaccination is the loss of vaccine activity during prolonged storage and transportation, especially in countries without secured cool chains. 9.3 Alternatives to Needles and Syringes

Dermal patches for transdermal diffusion of vaccines have been developed as an alternative to needles and syringes. However, the efficacy of these patches is limited by the low diffusion features of larger vaccines. Small molecules (<500 Da) may diffuse through the stratum corneum, the outer layer of the skin, but most of the vaccines are much larger (up to a million Da). The stratum corneum is, therefore, the natural barrier, which has to be overcome by the diffusion or penetration capability by vaccination procedures. There are other approaches to deliver vaccines through the stratum corneum, such as electroporation (Prausnitz and Langer, 2008) or the use of biolistic microparticle delivery systems (Kendall et al., 2004). Those approaches are expensive and result in unappreciated painful irritations of the skin (Denet et al., 2004; Wallace et al., 2009; Zhou et al., 2008).