Intellectual Merit:

The overarching goal of this project was to study the fluid dynamics of needle-free intradermal jet injection, which is an alternative method to deliver drugs to the skin without using standard hypodermic needles. The original motivation for this project stems from a confluence of needle-phobia, accidental needle-stick injuries, and poor outcomes in terms of immune response for novel nucleic acid vaccines delivered by needles. The specific aims of the project were: (1) Understand the role of fluid rheology in jet characteristics; (2) Define the criteria for maintaining jet coherency; (3) Determine the factors limiting bleb growth and maximum size. The most significant findings under these guiding aims are as follows:

1. High viscosity drugs can be delivered. For spring-powered jet injectors, the hydrodynamic performance was characterized as a function of fluid viscosity, and we determined that even high-viscosity fluids can be delivered effectively with jet injectors. This is particularly important for a range of biologic drugs such as high-concentration DNA vaccines that have high viscosity.
2. Higher viscosity fluids lead to more slender, collimated jet streams. whilst low viscosity water-like fluids result in dispersed turbulent jets. However, the stream collimation is not the only factor that determines whether an injection is successful; there is a confluence of spring force, fluid viscosity, and stand-off distance between the injector and the patient skin.
3. The force with which an injector is pressed against the skin is a key variable. The load (force used to push into the skin) determines the efficiency of an injection; It was found that a range of approximately 5-10 N provides optimal injection efficiency (i.e. how much drug gets correctly deposited below the skin).
4. Smooth contraction geometries are optimal. Using computational fluid dynamics (CFD) simulations, we studied the effect of geometry. Specifically, the tapering region from the main cartridge barrel to the orifice is important, and a smooth hyperbolic contraction was found to yield acceptable jet speeds with the lowest driving force.
5. Parameters to optimize percentage delivery were found. Through extensive investigations using excised skin tissue (guinea pig, pig, human), we determined injection efficiencies for a range of configurations and elucidated the most important factors for increasing drug delivery to the skin. It was found that: (i) zero stand-off should be used (i.e., the device must be pressed directly against the skin), (ii) the device should be oriented perpendicular to the skin (i.e. at 90-degrees), (iii) an attachment to induce a wide contact area can improve lateral dispersion within the dermal tissues.
6. Dual-depth injections are possible. We showed that a dual-orifice injector could facilitate simultaneous delivery to both intradermal (skin) and intramuscular (muscle) tissue, by using a custom-design ampoule with one narrow and one wide orifice.

Broader Impacts:

Throughout the course of this project, the principal impact to society has been the training and development of multiple young scientists. Notably, two doctoral students completed their PHD dissertations as a direct result of this project. In addition, twelve undergraduate students have taken part in multiple semesters of research, received training in good scientific practice, and have co-authored peer-reviewed scientific articles. Multiple scientific papers have been published and conference presentations have been made to disseminate the results of the work to a broad scientific audience. Aside from the development of personnel in science, our findings have the scope to improve needle-free drug delivery, especially for novel vaccines and therapeutic drugs.

Last Modified: 09/10/2024
Modified by: Jeremy O Marston