Project summary Injectable drugs constitute a $400+ billion market worldwide, and the range of devices for delivery is expanding to improve factors such as patient compliance, reduced pain, self-administration, and delivery efficiency. Intradermal delivery is especially pertinent in this regard for potential confluences of reduced pain, fast immune response and fractional dose vaccination. Also high on the priority list for delivery technologies are nucleic acids, which are seen as promising biological drugs for a range of immune disorders and infectious diseases. There are currently over 900 biological drugs on the market or in development. Amongst these, plasmid DNA vaccines have been widely studied over the last two decades and are being developed for Ebola, MERS, Zika, Hepatitis B, and HIV. However, a major obstacle is the method of delivery due to the large physical size of the molecules, which can render products that are high-viscosity, creating issues for injectability with standard hypodermic needles. This exploratory grant will develop prototype devices, based on blister-pack concepts, for intradermal injection of viscous suspensions, with the primary target being DNA products. Guided by approaches using hollow microneedles, we will fabricate and test single-orifice and multi-orifice modules that target intradermal delivery. The prototypes will be tested across a broad range of fluid viscosities and existing drugs. The proposed study comprises a proof-of-concept for our devices using ex-vivo tissues, and limited in-vivo studies using guinea pigs, a clinically relevant model for intradermal delivery. The overarching goal is to optimize intradermal delivery, specifically with regards to high-viscosity products in order to advance the feasibility of widespread DNA vaccination.