Needle-free injection of microparticle-laden suspension into soft hydrogel: jet penetration dynamics and particle dispersion patterns

Polymeric microparticles have been widely used as carriers for encapsulating and delivering drugs into different regions under the skin, finding applications in management of skin diseases. Although needle-based injections have been extensively explored for microparticle delivery, they are associated with limitations such as pain, risk of infection, and formulation challenges. Alternative, patient-friendly transdermal delivery methods are therefore of significant interest. In this study, we evaluated the feasibility of using a needle-free injection system (Biojector® 2000) to deliver polystyrene microparticle suspensions into agarose hydrogel as a skin-mimicking substrate. We systematically investigated the effects of particle size, concentration, gel stiffness, and standoff distance on penetration dynamics and particle dispersion. We demonstrated that the injector successfully delivered particles up to 50 µm, with smaller particles producing denser dispersions, and higher particle concentrations (0.05% w/v) enhancing kinetic energy retention and full-penetration events. Gel stiffness had the most pronounced effect: stiffer gels slowed penetration, reduced initial jet tip velocity, and constrained particle trajectories, whereas softer gels allowed for faster penetration and wider dispersion. Variation in standoff distance had minimal impact on penetration or dispersion profiles. These findings can inform future efforts to optimise needle-free microparticle delivery in animal or human skin models, supporting the advancement of microparticle-based drug delivery toward clinical application.