Microfluidic Jet Injections Enable Precise Needle-free Delivery of Insulin and Liposomes into Human Ex Vivo Skin

Needle-free injections offer a promising alternative to traditional needle-based drug delivery, addressing issues such as patient compliance, environmental burden, and safety concerns. This study investigates the precise delivery of insulin and liposomes into human ex vivo skin using microfluidic jet injections and evaluates their penetration depth and drug distribution using skin section based microscopic analysis. We show that our system reliably performs intradermal injections with high precision and minimal tissue damage. Compared to microneedles and solid needles, jet injections achieved similar or better delivery with less tissue disruption. Using fluorescence-based skin section analysis, we identified and monitored the distribution of insulin and liposomes within the skin. For insulin, jet injections enabled delivery into deeper skin layers, with penetration depths reaching up to 400 µm after 100 injections, compared to 150 µm and 50 µm for 50 and 25 injections, respectively. In contrast, for liposomes, jet injection primarily resulted in increased fluorescence intensity and accumulation in the epidermal layer compared to topical application, without a statistically significant increase in signal in the dermal layer. These findings indicate that, while jet number modulates delivery depth for small molecules such as insulin, liposome delivery is predominantly localized in more superficial skin layers. Therefore, we employed in this study two complimentary advanced, non-destructive, imaging techniques: confocal laser scanning microscopy (CLSM) and visible-light spectroscopic optical coherence tomography (vis-sOCT) with spectral contrast enhancement. These techniques validated the injectate localization, pathways, and skin barrier effects, highlighting vis-sOCT's potential for non-invasive in vivo applications. Our findings advance the understanding of microfluidic jet injections and establish a foundation for their integration with non-invasive imaging in clinical settings. These results support the development of microfluidic jet injection systems for targeted delivery applications, particularly where enhanced epidermal localization or tunable intradermal delivery is desired.