ABSTRACT

ABSTRACT Millions of people die each year from infectious disease, and many more are affected by allergies. A major stumbling block to the full use of improved immunotherapies (e.g., vaccines) against these problems is our limited ability to deliver genes and drugs to the required sites in the body. Specifically, effective methods to deliver genes and drugs into outer skin and mucosal layers (sites with immunological, physical, and practical advantages that cannot be targeted via traditional delivery methods) are lacking. This chapter investigates this particular challenge for physical delivery approaches. The skin’s structural and immunogenic properties are examined in the context of the physical cell targeting requirements of the viable epidermis. Selected current physical cell targeting technologies engineered to meet these needs are examined: needle and syringe, diffusion patches, liquid jet injectors, microneedle arrays/patches, and biolistic particle delivery. The focus then moves to biolistic particle delivery: we first analyze engineering these systems to meet demanding clinical needs. The interaction of biolistic devices with the skin is also examined, focusing on the mechanical interactions of ballistic impact and cell death. Finally, the current clinical outcomes of one key application of engineered delivery devices-DNA vaccines-are discussed.