Loading effects on the performance of needle-free jet injections in different skin models

Abstract

Intradermal delivery of vaccines with jet injection is one of the leading alternatives to conventional delivery with hypodermic needles via the Mantoux technique. However, for a given fluid, the effects of various parameters related to injector design, as well as skin properties are still not well understood. Whilst the key design parameters are orifice diameter, jet speed, ampoule volume, and standoff distances, we must also consider applied load of the device on the skin, and axial skin tension. These parameters are all studied herein using different ex-vivo models (guinea pig, pig and human skin) and different fluid viscosities. We find that the applied load can have a significant effect on the amount of drug delivered through the skin, as well as the fluid dispersion pattern in the intradermal tissues. Regardless of skin type or fluid viscosity, we show that minimal standoff and applied loads of approximately 1 kg should be used to maximize injection efficiency when targeting intradermal tissue.

Effect of air pockets in drug delivery via jet injections

“…As shown in earlier studies, higher percentage delivery was obtained for jet injection of liquid in lower volumes [35]. It was hypothesized that there is a limit of liquid volume which can be injected into the skin without significant rejection.…”

“…A spring-based jet injector (Bioject ID pen) was used in the experiments, which is described in de-tail in other works [33,34,35], but comprises a stiff spring piston with a cartridge with an orifice of diameter, d o ∼157 µm. DI water was filled in a transparent nozzle cartridge with a volume capacity of 0.11 ml.…”

“…The thickness of the dermis layer of porcine skin harvested from different pigs (hence, different colors in figure 6) was within 3 mm. The effect of force exerted by the jet injector (loading) in the normal and axial direction during injection has been reported in an earlier study [35], and therefore we used a recommended normal load of 1 kg for the maximum delivery efficiency at which the injection was actuated.…”

Microfluidic jet impact: spreading, splashing, soft substrate deformation and injection

“…The mechanical response of skin is dependent on measurement type, leading to reported skin stiffness values ranging from 1 MPa -1 GPa [24,25]. Additionally, skin's poro-viscoelastic behavior causes a portion of the injected liquid to be ejected during, or after, injection, due to the elastic recovery of the material (squeeze-out) [26][27][28][29]. Multiple papers show how jet parameters relate to injection depth [15,26,30,31], dispersion [26,[31][32][33], and delivery efficiency [17,26,31].…”

“…Additionally, skin's poro-viscoelastic behavior causes a portion of the injected liquid to be ejected during, or after, injection, due to the elastic recovery of the material (squeeze-out) [26][27][28][29]. Multiple papers show how jet parameters relate to injection depth [15,26,30,31], dispersion [26,[31][32][33], and delivery efficiency [17,26,31]. However, a detailed study of the impact behavior, especially the breakup of a jet upon impact (splashing) and squeeze-out at the microscale is lacking.…”