Picoliter ice particles by supersonic cryogenic jets for transdermal drug delivery: Extracellular vesicle application for skin diseases

Transdermal drug delivery holds significant potential for treating skin conditions. Conventional methods utilizing needles or large unit drug delivery volumes often result in patient discomfort and inhomogeneous delivery. This study proposes a picoliter ice particle delivery (PIPD) technology that produces high-speed solid ice drug particles using controlled supersonic cryogenic jets for transdermal drug delivery. The proposed PIPD system simultaneously atomizes liquid drug to micro-droplets, freezes them to solid ice particles, and accelerates these particles to penetrate the skin barrier. All these processes occur within 300 μs, ensuring drug integrity. Notably, most of the particles exhibited volumes even below 1 picoliter. The average delivery efficiency of PIPD was found to be 50 % when used with ex vivo porcine skin, and in vivo mouse experiments suggest that PIPD's delivery efficiency to the dermis layer is comparable to traditional injection delivery. Stem cell-derived functional extracellular vesicles (EVs) did not show any reduction in their anti-inflammatory and regenerative cell absorption properties after PIPD. Consequently, PIPD EVs delivery led to significant therapeutic improvements in the wound and atopic dermatitis animal models.