No abstract

The 'Nanopatch' (NP) comprises arrays of densely packed projections with a defined geometry and distribution designed to physically target vaccines directly to thousands of epidermal and dermal antigen presenting cells (APCs). These miniaturized arrays are two orders of magnitude smaller than standard needles-which deliver most vaccines-and are also much smaller than current microneedle arrays. The NP is dry-coated with antigen, adjuvant, and/or DNA payloads. After the NP was pressed onto mouse skin, a protein payload co-localized with 91.4 + or - 4.1 APC mm(-2) (or 2925 in total) representing 52% of the delivery sites within the NP contact area, agreeing well with a probability-based model used to guide the device design; it then substantially increases as the antigen diffuses in the skin to many more cells. APC co-localizing with protein payloads rapidly disappears from the application area, suggesting APC migration. The NP also delivers DNA payloads leading to cutaneous expression of encoded proteins within 24 h. The efficiency of NP immunization is demonstrated using an inactivated whole chikungunya virus vaccine and a DNA-delivered attenuated West Nile virus vaccine. The NP thus offers a needle-free, versatile, highly effective vaccine delivery system that is potentially inexpensive and simple to use.

We introduce and describe a methodology for fabricating high-density and high aspect ratio micronanoprojection arrays-and further demonstrate the utility of these devices in targeting the skin for two different healthcare applications. The key to achieving the unprecedented high projection density (.20 000 cm 22 ) is the use of a controlled mixed plasma in a DRIE process, producing long, tapered tips without limiting the overall feature density. With a tailored process we produce structures of tuneable shape and height, with high uniformity across the face of silicon wafers. We show that these devices are suitable for both biological delivery and biomarker-specific extraction applications.

Coaxial electrospinning was used to encapsulate the complex hydride ammonia borane in polystyrene to improve its properties as a hydrogen storage material. A solvent selection system was developed by using the Hansen solubility parameters to facilitate the choice of compatible solvents for core and shell. This enabled systematic optimization of the parameters needed for successful coelectrospinning. This approach has general application for any multiphase electrospinning system, including ones where the core is highly conducting or nonpolymeric. The resulting fiber morphologies depend strongly on the degree of miscibility of core and shell solutions. Fibers spun from immiscible core-shell solutions had a classic coaxial structure. Fibers produced from semimiscible core-shell solutions were highly porous, with inclusions extending through the fiber and an ordered radial and longitudinal distribution of nanoscale pores on the fiber surface. We suggest that this type of porosity may be due to an instability created in the nonaxisymmetric modes at the core-shell interface, resulting in intrusion of the core into the shell polymer. These controllably porous structures have numerous potential applications including materials templating or drug delivery. In the porous fibers, the temperature of the first hydrogen release of ammonia borane is reduced to 85 °C. This result suggests a nanostructured hydride, but a large mass loss indicates that much of the ammonia borane is expelled on heating. The coaxial fibers, in contrast, appear to encapsulate the hydride successfully. The coaxial and porous fibers alike showed no significant release of borazine, suggesting two different suppression mechanisms for this impurity.