Systematic parametric analysis of drug properties and injection conditions in nebulized jet stream-mediated skin delivery.

The use of needle-free jet injection is an effective approach to enhance drug deposition in the skin. Although it has been employed in dermatological practice, the optimal drug selection and device settings have not yet been defined and standardized. This study aimed to assess the efficacy and safety of nebulized jet stream (NJS) delivery to provide evidence-based treatment recommendations. Passive delivery with a drug treatment duration of 0.5-3 h was also examined for comparison. In the in vitro permeation test (IVPT), NJS enhanced skin deposition of minoxidil, a hydrophilic permeant, by twofold compared to passive treatment for three hours. The skin deposition of dextran, used as a macromolecule model, demonstrated greater penetration with NJS than with passive delivery for 0.5-2 h. In contrast, NJS-delivered lipophilic permeants showed lower skin deposition than passive delivery. However, jet injection enabled the rapid formation of a drug depot within 30 s. NJS also achieved significant follicular uptake of the drug. Fluorescence and confocal microscopies revealed that NJS delivered both hydrophilic and lipophilic dyes to depths corresponding to the epidermis and upper dermis. The permeants in the superficial layer could subsequently diffuse to deeper skin strata. Shot volume and operating pressure showed a positive correlation with minoxidil penetration. This effect was less significant for lidocaine as a lipophilic drug model, suggesting possible saturation of the drug reservoir in the skin. Microscopic observation showed negligible changes in skin appearance and structure after jet exposure. The in vivo safety assay demonstrated that NJS application on nude mouse skin was well tolerated, and the mild erythema caused by 20 shots resolved in six hours. NJS-mediated skin delivery holds potential for dermatological use, offering reliable and safe drug penetration.