Characterizing the roles of drug viscosity and tissue biomechanics in needle-free injection performance using skin-mimicking models

Abstract

Purpose: Needle-free jet injectors (NFJIs) have garnered growing attention in drug delivery applications owing to their ability to minimize the discomfort associated with conventional needle-based syringes. This study examines the key factors governing NFJI performance, with a particular focus on the interplay between formulation viscosity and skin biomechanics. As injectable drugs often consist of concentrated solutions with viscosities exceeding 100 mPa·s, understanding the influence of fluid viscosity is critical. Methods: To this end, we systematically evaluated the impact of viscosity on NFJI performance using glycerol, carboxymethyl cellulose (CMC), and bovine serum albumin (BSA) as representative Newtonian fluids, non-Newtonian fluids, and protein drugs, respectively. The mechanical properties of human skin across different anatomical sites were characterized, and gelatin-based hydrogels mimicking skin elasticity were developed as model substrates. Results: For Newtonian fluids, increasing viscosity reduced jet penetration depth, stagnation pressure, and velocity. In contrast, non-Newtonian fluids such as CMC exhibited stable penetration with increasing viscosities owing to their shear-thinning behavior. For protein formulations, elevated concentrations increased the risk of aggregation but maintained structural stability during injection. Moreover, greater medium elasticity amplified stagnation pressure losses, further reducing penetration depth in Newtonian fluids. Meanwhile, non-Newtonian fluids maintained stable penetration performance through shear-responsive viscosity adaptation. Conclusion: These findings underscore the need to consider both fluid rheology and tissue biomechanics in NFJI system design, offering a framework for optimizing injection performance across diverse formulations and viscosity conditions.