High-pressure microjet system enhances epidermal delivery of hydrophilic actives

Background: The stratum corneum is the principal barrier limiting topical delivery of hydrophilic molecules. We hypothesized that high-pressure microjet (HPMJ) systems would enhance epidermal deposition without breaching the dermis. Methods: The efficacy of a handheld HPMJ device (K-Stream) for epidermal drug delivery was evaluated in: (i) Ex vivo human skin explants treated with Lucifer Yellow, with dye distribution quantified in the stratum corneum, suprabasal, and basal layers by fluorescence microscopy, (ii) Ex vivo caffeine penetration assessed by confocal Raman spectroscopy with depth-resolved mapping of caffeine-specific spectra, and (iii) A randomized, split-face, 14-day in vivo trial (n = 23) comparing changes in stratum corneum hydration after twice-daily application of serum via HPMJ or manual massage. Results: In the ex vivo fluorescence study, HPMJ application increased Lucifer Yellow in the suprabasal layers by up to approximately 4-fold versus manual application (e.g., +412% at 6 h, p < 0.01). Raman spectroscopy demonstrated at 4 h caffeine signal was confined to the outermost ∼20 μm with manual application, whereas HPMJ produced detectable caffeine spectra down to 60 μm without signal in the dermis. In vivo the HPMJ-treated side exhibited a significantly greater and faster hydration over 14 days. At day 14, hydration on the HPMJ side exceeded the manual side by ∼6 units (p = 0.003). No treatment-related adverse events were observed. Conclusions: HPMJ increases epidermal delivery depth and functional hydration relative to manual application of the same formulation. These data support HPMJ as a non-invasive platform for enhancing epidermal delivery of hydrophilic actives, while highlighting the need for larger, mechanistic studies.