Intradermal DNA vaccine delivery using vacuum-controlled, needle-free electroporation.

Intradermal delivery of DNA vaccines via electroporation (ID-EP) has shown clinical promise, but the use of needle electrodes is typically required to achieve consistent results. Here, delivery of a DNA vaccine targeting the Middle East Respiratory Syndrome Coronavirus (MERS-CoV) is achieved using noninvasive intradermal vacuum-EP (ID-VEP), which functions by pulling a small volume of skin tissue into a vacuum chamber containing noninvasive electrodes to perform EP at the injection site. Gene expression and immunogenicity correlated with EP parameters and vacuum chamber geometry in guinea pigs. ID-VEP generated potent humoral and cellular immune responses across multiple studies, while vacuum (without EP) greatly enhanced localized transfection but did not improve immunogenicity. Because EP was performed noninvasively, the only treatment site reaction observed was transient redness, and ID-VEP immune responses were comparable to a clinical needle-based ID-EP device. The ID-VEP delivery procedure is straightforward and highly repeatable, without any dependence on operator technique. This work demonstrates a novel, reliable, and needle-free delivery method for DNA vaccines.

Transient modelling of impact driven needle-free injectors.

Needle-free jet injectors (NFJIs) are one of the alternatives to hypodermic needles for transdermal drug delivery. These devices use a high-velocity jet stream to puncture the skin and deposit drugs in subcutaneous tissue. NFJIs typically exhibit two phases of jet injection - namely - an initial peak-pressure phase (< 5 ms), followed by a constant jet speed injection phase (≳ 5 ms). In NFJIs, jet velocity and jet diameter are tailored to achieve the required penetration depth for a particular target tissue (e.g., intradermal, intramuscular, etc.). Jet diameter and jet velocity, together with the injectant volume, guide the design of the NFJI cartridge and thus the required driving pressure. For device manufacturers, it is important to rapidly and accurately estimate the cartridge pressure and jet velocities to ensure devices can achieve the correct operational conditions and reach the target tissue. And thus, we seek to understand how cartridge design and fluid properties affect the jet velocity and pressure profiles in this process. Starting with experimental plunger displacement data, transient numerical simulations were performed to study the jet velocity profile and stagnation pressure profile. We observe that fluid viscosity and cartridge-plunger friction are the two most important considerations in tailoring the cartridge geometry to achieve a given jet velocity. Using empirical correlations for the pressure loss for a given cartridge geometry, we extend the applicability of an existing mathematical approach to accurately predict the jet hydrodynamics. By studying a range of cartridge geometries such as asymmetric sigmoid contractions, we see that the power of actuation sources and nozzle geometry can be tailored to deliver drugs with different fluid viscosities to the intradermal region.

Computational study of fluid flow in tapered orifices for needle-free injectors.

Transdermal drug delivery using spring-powered jet injection has been studied for several decades and continues to be highly sought after due to the advent of targeted needle-free techniques, especially for viscous and complex fluids. As such, this paper reports results from numerical simulations to study the role of fluid rheology and cartridge geometry on characteristics such as jet exit velocity, total pressure drop and boundary layer thickness, since these all factor in to jet stability and collimation. The numerical approach involves incompressible steady flow with turbulence modelling based on the system Reynolds number at the orifice (Re = ρdovj/µ). The results are experimentally validated for a given geometry over a wide range of Reynolds numbers (101 < Re < 104), and our results indicate a sharp decrease in dimensionless pressure drop (Eu = 2∆P/ρvj2) for Re < 102) and gradually approaching the inviscid limit at Re ≥ 104. By extending the study to non-Newtonian fluids, whose rheological profile is approximated by the Carreau model, we also elucidated the effect of different rheological parameters. Lastly by studying a range of nozzle geometries such as conical, sigmoid taper and multi-tier tapers, we observe that fluid acceleration suppresses the boundary layer growth, which indicates there may be optimal geometries for creating jets to target specific tissue depths.