Skin is an attractive target for delivery of genetic therapies and vaccines. However, new approaches are needed to access this tissue more effectively. Here, we describe a new delivery technology based on arrays of structurally precise, micron-scale silicon projections, which we term microenhancer arrays (MEAs). In a human clinical study, these devices effectively breached the skin barrier, allowing direct access to the epidermis with minimal associated discomfort and skin irritation. In a mouse model, MEA-based delivery enabled topical gene transfer resulting in reporter gene activity up to 2,800-fold above topical controls. MEA-based delivery enabled topical immunization with naked plasmid DNA, inducing stronger and less variable immune responses than via needle-based injections, and reduced the number of immunizations required for full seroconversion. Together, the results provide the first in vivo use of microfabricated devices to breach the skin barrier and deliver vaccines topically, suggesting significant clinical and practical advantages over existing technologies.

Plasma-enhanced chemical vapor deposition (PECVD) of SiOx thin coatings on polymer surfaces yields tough hybrid materials with the gas barrier properties and transparency of glass. Combination of these properties makes these materials ideally suited for food packaging and biomedical device applications. In this study, we employ a Non-Parametric Response Surface Methods optimization to identify the Magnetron-PECVD conditions responsible for superlative SiOx barrier coatings on poly(ethylene terephthalate) (PET). Oxygen and water vapor permeances of optimized PET/SiOx composites produced by hexamethyldisiloxane and trimethylsilane have been measured as functions of temperature and are found to exhibit Arrhenius behavior. The thermal activation energy for water vapor permeation, unlike that for oxygen permeation, depends on barrier performance and increases by as much as 20 kJ/mol with an increase in barrier efficacy. Examination of these materials by phase-imaging atomic force microscopy and energy-filtered transmission electron microscopy reveals a correlation between SiOx morphology (including defects) and barrier performance. Morphological and permeation results are compared to identify some of the physical factors governing water vapor permeation through SiOx-modified polymers.

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Poly(ethylene terephthalate) substrates were coated with thin films of silicon oxide deposited by magnetically enhanced chemical vapor deposition. The rates of oxygen and water vapor transport through the coated and uncoated film systems were obtained as a function of temperature. Activated rate theory treatment of oxygen transmission rates revealed that the silicon oxide coatings were imperfect; the apparent free energies of activation (∆E p ) for transport through film substrates which were coated on a single side were statistically identical to uncoated controls. However, coating both sides of the polymer substrate with identical oxide layers resulted in a 54 kJ/mol increase in the ∆E p value. A simple empirical model for the change in transport mechanism is offered to explain this unanticipated result. Analogous treatment of water vapor transport rates for these same film systems showed no obvious change in transport mechanism. However, ∆E p values obtained for water vapor permeation through silicon oxide-coated poly(ethylene terephthalate), polystyrene, polypropylene, and polycarbonate substrates were identical within experimental error, suggesting attractive interaction between the oxide layer(s) and water.