Safety Profile of Solanum tuberosum-Derived Exosomes: Evidence from In Vitro Experiments and Human Skin Tests

<b>Background/Objectives:</b> Potato (<i>Solanum tuberosum</i>)-derived exosomes (SDEs) are extracellular vesicles (66 nm in diameter) with therapeutic potential. SDEs suppress matrix metallopeptidases (<i>MMP</i>s) 1, 2, and 9, tumor necrosis factor (<i>TNF</i>), and interleukin 6 (<i>IL6</i>), while exhibiting radical-scavenging activity against the free radical 2,2-diphenyl-1-picrylhydrazyl (DPPH) in vitro and mitigating hydrogen peroxide (H₂O₂)-induced oxidative stress in HaCaT cells. SDEs upregulate the antioxidant gene glutathione S-transferase alpha 4 (<i>GSTA4</i>), prevent UVB damage, and regenerate photodamaged HaCaT cells. This study evaluates SDEs' safety and skin-enhancing properties to improve their beauty-related and medical applications. <b>Methods:</b> The SDEs purified via ultracentrifugation were tested for their cytotoxic effects on HaCaT cell viability in scratch wound healing assays and for skin barrier gene modulation in HaCaT keratinocytes and Detroit 551 fibroblasts. A reverse transcription-polymerase chain reaction (RT-PCR) was used to analyze the changes in skin barrier gene expression following the SDE treatment. Cosmetic prototypes containing SDEs were assessed for skin irritation, cooling effects, periorbital wrinkle reduction, elasticity, and whitening properties. <b>Results:</b> The cytotoxicity and human topical tests confirmed the safety of SDE application. The SDEs accelerated wound closure, elevated the skin barrier gene expression level, and improved the clinical parameters, including wrinkle reduction, elasticity enhancement, and whitening. No irritation or side effects were observed. <b>Conclusions:</b> This study identified natural, edible potato-derived exosomes (SDEs) as highly safe agents that significantly enhance wound healing and promote skin barrier-related gene expression. Their multifunctional anti-aging efficacy-reducing wrinkles, enhancing elasticity, and promoting whitening without irritation-positions them as promising candidates for cosmetic and dermatological innovations. These findings warrant further exploration of SDEs for therapeutic applications, including inflammatory skin disorders and drug delivery systems.