Clinical endpoints of needle-free jet injector treatment: An in depth understanding of immediate skin responses

Abstract

Objectives: Needle-free jet injectors have been used in dermatological practice for many years. However, predefined clinical endpoints that guide physicians to choose optimal device settings have not been clearly defined. Here, we evaluate immediate skin responses as clinical endpoints for needle-free jet injector treatments.

Methods: We injected methylene blue in ex vivo human skin using an electronically-controllable pneumatic injector (EPI; 3-6 bar, 50-130 µl; n = 63), and a spring-loaded jet injector (SLI) with fixed settings (100 µl; n = 9). We measured the immediate skin papule (3D-camera), residual surface fluid (pipette), dermal dye distribution by estimating depth and width, and subcutaneous dye deposition.

Results: EPI with 4 bar and 100 µl resulted in the largest skin papule of 48.7 mm³ (35.4-62.6 mm³ ) and widest dermal distribution of 8.0 mm (5.5-9.0 mm) compared to EPI with 6 bar and 100 µl (p < 0.001, p = 0.018, respectively). The skin papule volume showed a significant moderate to high positive correlation with the width and depth of dye distribution in the dermis (r_s = 0.63, r_s = 0.58, respectively; p < 0.001 for both correlations). SLI showed high variability for all outcome measures. Finally, a trend was observed that a small skin papule (≤7 mm) and little residual surface fluid (≤10% of injection volume) were warning signs for subcutaneous deposition.

Conclusions: The immediate skin papule and residual surface fluid correspond with dermal drug deposition and are relevant clinical endpoints for needle-free jet injector treatments in dermatological practice.

Keywords: dermatology; drug delivery; injection; intralesional; jet injection; needle-free injection; pneumatic injection.

Figure 1

Residual fluid on skin surface and the immediate skin papule are clinical endpoints of needle‐free jet injector treatments, and relate to the intradermal spatial dye distribution. Needle injection served as control. EPI, electronic pneumatic injection; NI, needle injection; SLI, spring‐loaded jet injection

Figure 2

Boxplot presenting the median and interquartile ranges with min/max whiskers of the skin papule volume in mm³ for all interventions. EPI with 4 bar and 100 µl resulted in the largest immediate skin papule. High variability in skin papule volume was observed for SLI. Needle injection served as control. EPI with 4 bar and 100 µl is presented in duplicate. EPI, electronic pneumatic injection; NI, needle injection; SLI, spring‐loaded jet injection

Figure 3

Representative clinical photographs of the residual surface fluid as clinical endpoint after injection with an electronically‐controllable pneumatic injector (EPI) with methylene blue dye (blue). (A) High residual surface fluid volume of 21 µl after EPI with 3 bar and 100 µl, which is visually distinguishable from (B) with a low residual surface fluid volume of 9 µl after EPI with 6 bar and 100 µl

Figure 4

(A, B) Boxplots presenting the median and interquartile ranges with min/max whiskers of needle‐free jet injector induced dermal dye distribution in width (A) and depth (B) for all interventions. EPI with 4 bar and 100 µl resulted in the largest dermal distribution. SLI showed high variability for intradermal dye distribution in depth and width. Needle injection served as control. The boxplot includes outliers and EPI with 4 bar and 100 µl is presented in duplicate. EPI, electronic pneumatic injection; NI, needle injection; SLI, spring‐loaded jet injection