Toward Pain-Free Supersonic Microjets: Design and Validation of a 3D-Printed VeroWhitePlus Micro-CD Nozzle for High-Precision Needle-Free Drug Delivery

Despite being developed as painless alternatives to hypodermic needles, most needle-free jet injectors generate excessive localized pressures that disrupt tissue integrity and compromise patient comfort. This limitation persists in existing commercial systems due to uncontrolled jet dynamics and rigid actuator configurations. Herein, a VeroWhitePlus-based microconverging–diverging (VWP-Micro-CD) nozzle was designed and 3D-printed, integrating materials engineering with statistical and fluid-dynamic optimization to produce finely tuned therapeutic microjets. Inspired by spacecraft propulsion principles, the system precisely regulates supersonic jet expansion to achieve energy-efficient, low-pressure, and minimally invasive drug delivery. Using Latin hypercube sampling, the nozzle geometry was optimized to generate a supersonic jet (Mach ≈ 3) with an area ratio of ∼3.90 and convergent/divergent angles of 21° and 8°, respectively. Computational fluid dynamics and pressure–force analyses verified efficient flow acceleration at reduced driving pressures (≈2 and 3 MPa). In vivo validation confirmed controlled dermal penetration (∼1500 μm) and systemic uptake of dexamethasone sodium phosphate, verified through liquid chromatography–mass spectrometry (LC–MS). Collectively, the results position the VWP-Micro-CD nozzle as a next-generation platform for precise, painless, and cost-effective transdermal and subcutaneous drug delivery, uniting material innovation with aerodynamic optimization.