Work

Ascorbic acid formulation using milk-derived extracellular vesicles: a stepwise process evaluation

Year: 2026

Type: article

Abstract: Labile hydrophilic compounds, such as ascorbic acid (AA), present challenges for nanoscale formulation due to their chemical instability and strong tendency to recrystallize during processing and storage. Although various nanocarrier-based formulation approaches have been developed, achieving physical stability while maintaining biological compatibility remains difficult. In this study, we aimed to develop a practical and biocompatible formulation approach using milk-derived extracellular vesicles (mi-EVs) and to establish a solvent-free formulation strategy through stepwise evaluation of processing conditions. An AA formulation based on mi-EVs (milkCsome) was developed through sequential evaluation of key processing parameters. Sequential physical treatment—sonication followed by rotation—improved the visual homogeneity of the formulation, with no visible precipitation observed after 16 h of storage at 4 °C under the selected conditions. Under the selected processing conditions, milkCsome achieved approximately 16% AA retention after purification and retained antioxidant activity. Biological evaluations showed no detectable reduction in cell viability under the tested conditions, and the formulation was classified as non-irritant in a reconstructed human skin model. Overall, this study presents a simple, solvent-free process for preparing a milk-derived extracellular vesicle-based AA formulation with antioxidant activity and biological compatibility under the conditions tested.

Source: Scientific Reports

DOI: 10.1038/s41598-026-75650-6