The effect of strain rate on the precision of penetration of short densely-packed microprojection array patches coated with vaccine

If skin's non-linear viscoelastic properties are mechanically exploited for precise antigen placement, there is tremendous promise for improved vaccines. To achieve this, we designed a Nanopatch™-densely packed micro-nanoprojections (>20,000/cm²) to directly deposit antigen to large numbers of epidermal Langerhans cells and dermal dendritic cells. Here, we controllably applied our Nanopatches™ with discrete conditions between peak strain rates of ∼100 s^-1-7000 s^-1 and quantified resulting penetration depths, delivery payloads and skin mechanics. Increasing the strain rate of application, we overcame key skin variability, achieving increases in both projection penetration depth (by over 50% length) and area coverage of a full array (from 50% to 100%). This delivery depth precision opens the way for more fully utilizing the skin's immune function. Furthermore, we yielded new insights on mechanical behaviour of skin, including: 1) internal skin property changes that could affect/facilitate penetration; 2) projection design to dictate penetration depth; 3) puncture mechanics of skin in this strain rate range. Indeed, we show delivery of a model vaccine using our tested range of strain rates achieved functionally relevant tunable systemic antibody generation in mice. These findings could be of great utility in extending skin strata vaccine targeting approaches to human use.